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suggesting that there is a &#8220;window of opportunity&#8221; at this stage&#44; referring to the first few months since onset&#44; when the patient is considered most likely to respond to treatment than in more advanced stages&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Due to this&#44; early diagnosis and treatment is essential&#44; thereby increasing the possibility of controlling the inflammation and reducing damage&#46; As a result&#44; RA management and prognosis have drastically changed in recent years&#46; The main objectives is to achieve complete remission or at least a low stable activity&#44; improving functional prognosis of the patient by employing a treat to target strategy&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Also&#44; during management we must not forget pain control&#44; and the reduction of corticosteroids or preferably their discontinuation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Current therapeutic strategies include treatments aimed at fast pain and inflammation control and disease-modifying anti-rheumatic drugs &#40;DMARDs&#41; which may be synthetic &#40;sDMARDs&#41; or biologic &#40;bDMARDs&#41; &#40;anti-TNF&#44; other biologics and new targeted therapies&#41;&#46; Their use should be introduced as soon as possible during the course of the disease&#44; in full doses&#44; alone or in combination so as to increase the therapeutic efficacy covered by the treat to target strategy&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The lack of standardised forms of different treatment usage has lead to different combinations being used&#46; These depend both on the physician and the availability of the drugs as well as the individual characteristics of each patient&#46; The change in therapeutic objectives and the broadening of treatment options have determined multiple possibilities for patient management in daily clinical practice&#46; Clinical trial data abound in the literature<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> but not in real life&#46; As a result&#44; our aim was to obtain clinical practice information regarding recent onset RA&#46; We will describe the clinical management and treatment&#44; its persistence&#44; and the reasons for discontinuation in a cohort of patients with recent onset RA in conditions of daily clinical practice followed up in an outpatient rheumatology unit consultation of a tertiary hospital&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0025" class="elsevierStylePara elsevierViewall">A retrospective&#44; longitudinal&#44; observational study&#46; It included patients diagnosed with RA between 01&#47;01&#47;07 and 31&#47;12&#47;14&#46; Follow-up included up to the loss of follow-up or the end of the study &#40;01&#47;01&#47;17&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Scope of the study</span><p id="par0030" class="elsevierStylePara elsevierViewall">Rheumatology Unit of the Hospital Cl&#237;nico San Carlos&#44; which is a tertiary public hospital with a catchment area serving approximately 600&#44;000 people&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Subjects</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients over 16 diagnosed with RA were included &#40;ACR&#47;EULAR 2010 criteria&#41;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> less than one year prior to inclusion&#46; To enter into the study it was necessary for the patient to sign the informed consent form&#44; have completed at least 2 visits to the rheumatology unit and to have received at least one sDMARD &#40;chloroquine&#44; hydroxychloroquine&#44; methotrexate&#44; leflunomide&#44; gold injections&#44; sulfasalazine&#44; cyclosporine&#44; cyslophosphamide&#44; azathioprine&#44; mycophenolate mofetil&#41; or a bDMARD &#40;infliximab&#44; adalimumab&#44; etanercept&#44; golimumab&#44; certolizumab pegol&#44; rituximab&#44; abatacept&#44; tocilizumab&#41; during the inclusion period&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This study was approved by the ethics and institutional clinical trial committee of the Hospital Cl&#237;nico San Carlos&#46; Also&#44; according to their indications&#44; it referred to the Spanish Medicine Agency&#44; which classified it as an observational study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data sources</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patient data were collected through the departmental electronic clinical records of the rheumatology unit of the Hospital Clinic San Carlos where routine visits were recorded in &#8220;real time&#8221;&#46; Furthermore&#44; written clinical files were reviewed to complete data which was lacking&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Variables</span><p id="par0050" class="elsevierStylePara elsevierViewall">1&#41; Sociodemographic&#58; age&#44; sex&#44; civil status&#44; level of education&#44; category&#44; employment situation and residential situation &#40;alone&#44; family&#47;friends&#44; institutionalised&#41;&#46; 2&#41; Clinical&#58; a&#41; date of diagnosis&#44; b&#41; smoker&#44; c&#41; baseline quality of life measured by the Rosser index&#44; d&#41; analytics&#58; baseline sedimentation rate&#44; rheumatoid factor&#44; anti-citrullinated peptide antibodies&#44; e&#41; baseline disease activity measured through the HAQ and DAS 28&#46; 3&#41; Baseline comorbidity&#58; high blood pressure&#44; diabetes mellitus&#44; hypercholesterolaemia&#44; ischaemic cardiopathy&#44; congestive heart failure&#44; cerebrovascular pathology&#44; peripheral artery disease&#44; cancer and type of cancer&#44; depression&#44; gastroduodenal ulcer&#44; chronic obstructive pulmonary disease&#44; liver disease&#44; osteoporosis&#44; fractures&#44; kidney failure&#44; cognitive impairment and thyroid alterations&#46; 4&#41; sDMARDs&#58; type &#40;chloroquine&#44; hydroxychloroquine&#44; methotrexate&#44; leflunomide&#44; gold salts&#44; sulfasalazine&#44; cyclosporine&#44; cyslophosphamide&#44; azathioprine&#44; mycophenolate mofetil&#41;&#44; start and finish dates&#46; 5&#41; bDMARDs&#58; type &#40;infliximab&#44; adalimumab&#44; etanercept&#44; golimumab&#44; certolizumab pegol&#44; rituximab&#44; abatacept&#44; tocilizumab&#41;&#44; start and finish dates&#46; 6&#41; Concomitant treatments &#40;if they have been used for at least 3 months since the beginning of each treatment course with sDMARDs&#41;&#58; a&#41; use of opioids and anti-inflammatory analgesics&#44; b&#41; mean corticoid dose&#46; 7&#41; reasons for suspension of sDMARDs&#58; a&#41; adverse event &#40;AE&#41;&#58; the type&#44; severity and relationship with the drug were recorded b&#41; inefficacy&#44; c&#41; patient&#8217;s decision&#44; e&#41; physician&#8217;s decision&#44; f&#41; remission or improvement defined by the criterion of the rheumatologist responsible for the patient&#44; g&#41; others &#40;including the desire for children or the suspension of programmed surgery for over 3 months&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">A descriptive analysis was performed of the subjects with sociodemographic and clinical characteristics&#44; treatments with tns DMARDs &#40;first and second line&#41;&#44; in monotherapy or combined therapies over time&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The reasons for discontinuation were described using frequencies&#44; mean and standard deviation&#44; medians or percentiles&#46; The persistence of treatment and the incidence of suspension were assessed using survival techniques&#44; expressed by100 patients&#47;year with a 95&#37; confidence interval&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All analysis was performed with the statistical programme Stata v&#46;13 <span class="elsevierStyleItalic">Special Edition&#8211;Statistics&#47;Data Analysis</span>&#46; A two-tailed <span class="elsevierStyleItalic">P</span> value under &#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Eight hundred and fourteen patients were included&#44; with a mean follow-up of 5 years &#40;median&#58; 5&#46;1 &#91;p25&#8722;75&#58; 2&#46;97&#8211;7&#46;12&#93;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> contains the sociodemographic and baseline clinical characteristics&#46; Over three quarters of the patients were women &#40;77&#46;52&#37;&#41; with a mean age at diagnosis of 57&#46;53 &#40;&#177;15&#46;50 years&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Mean time up to diagnosis was 8&#46;81 months &#40;&#177;226&#46;25&#41;&#44; achieving a diagnosis during the first visit in 72&#46;85&#37; of patients&#46; A higher percentage of patients were recorded who had never smoked compared with active or ex-smokers&#46; Approximately half of the patents presented with seropositive RA&#46; Regarding disease activity on diagnosis&#44; the median erythrocyte sedimentation rate was 42&#46;62 &#40;&#177;28&#46;14&#41; mm&#47;h and <span class="elsevierStyleItalic">DAS 28</span> mean was 5&#46;26&#8239;&#177;&#8239;1&#46;44&#46; Regarding measurement of quality of life using the Rosser index n diagnosis&#44; a mean of &#46;97&#8239;&#177;&#8239;&#46;04 was obtained&#46; Regarding comorbidity&#44; both blood pressure and hypercholesterolaemia were the most prevalent pathologies to be detected in over a third of patients on diagnosis&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Two thousand&#44; three hundred and eighty eight courses of treatment with DMARDs were registered in the 814 patients&#44; with mean time up until the first line of treatment at 21 &#91;0&#8211;43&#93; days&#46; The most commonly used drug was oral methotrexate followed by anti-malarial drugs &#40;see <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Combined therapy in our cohort was used in 40&#46;08&#37; &#40;dual therapy in 31&#46;87&#37;&#59; &#8805;3 drugs in 8&#46;25&#37;&#41; and biologics were used in 13&#46;65&#37; of treatments&#44; both as monotherapy and combined&#46; Regarding the way in which the DMARDs were used&#44; the most common was immunotherapy of sDMARDs &#40;57&#46;45&#37;&#41; followed by combined therapy of sDMARDs &#40;28&#46;89&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Concomitant treatments used were also collected&#46; In 83&#46;75&#37; of treatments these were associated with corticoids with a mean dose of 1&#46;20 &#40;&#177;&#8239;&#46;77&#41;&#8239;mg&#46; In 36&#46;06&#37; of treatments the concomitant use of non-steroid anti-inflammatory was recorded whilst that of opioids was much lower &#40;minor opioids 6&#46;74&#37; of courses&#59; major opioids 5&#46;65&#37; of courses&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">An analysis of drug combinations most commonly used was performed and we observed that the most used sDMARDs in monotherapy was methotrexate and in bDMARDs was etanercept&#59; regarding combined therapy&#44; in dual therapy the preferred combination of sDMARDs was methotrexate and hydroxychloroquine and that of sDMARDs with bDMARDs was methotrexate and adalimumab&#46; Regarding triple therapy&#44; in synthetics the preferred was methotrexate with hydroxychloroquine and leflunomide and in sDMARDs with bDMARDs was methotrexate with leflunomide and etanercept&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">This same analysis was repeated by course of treatment&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the first course of treatment&#46; During the first course&#44; monotherapy was most commonly used&#44; and within it&#44; monotherapy with sDMARDs&#44; especially methotrexate&#59; 4 cases of monotherapy with bDMARDs were recorded&#46; Regarding combined therapy&#44; in the first course of treatment&#44; its use was very low and was essentially given as dual&#44; or occasionally as triple therapy&#46; sDMARDs were almost always used&#59; a single case of a combination of sDMARDs and bDMARDs as the first course of treatment was recorded&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">In later courses of treatment we were able to appreciate several differences&#46; Regarding monotherapy&#44; the most used sDMARD was also methotrexate &#40;41&#46;22&#37;&#41; but there were differences in the bDMARDs&#44; since etanercept and adalimumab &#40;20&#37; both&#41; were used equally&#46; Combined therapy was used with greater frequency &#40;57&#46;05&#37;&#41;&#44; and within it dual therapy was particularly used &#40;78&#46;51&#37;&#41;&#46; In dual therapy essentially sDMARDs were used with methotrexate-hydroxychloroquine being the most used combination &#40;22&#46;18&#37;&#41; followed by methotrexate-chloroquine &#40;20&#46;93&#37;&#41;&#59; within dual therapy with biologics there was a more frequent use of methotrexate-adalimumab &#40;13&#46;70&#37;&#41; followed by leflunomide-etanercept &#40;9&#46;59&#37;&#41;&#46; Regarding triple therapy &#40;21&#46;49&#37;&#41;&#44; which was most frequently used as a combination of bDMARDs &#40;62&#46;18&#37;&#41;&#44; the most used was methotrexate-leflunomide-etanercept &#40;6&#46;67&#37;&#41;&#59; when triple therapy with sDMARDs was chosen&#44; the most used was the combination of methotrexate-leflunomide-hydroxychloroquine &#40;15&#46;07&#37;&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Discontinuations of 1094 of the 2388 courses of treatment were recorded in 361 patients&#44; 150 due to inefficacy in 110 patients&#44; 124 due to the physician&#8217;s decision in 102 patients&#44; 66 due to improvement in 61 patients&#44; 116 due to the patient&#8217;s decision in 103 patients and 54 due to other causes in 51 patients&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The incidence of discontinuation in our cohort was estimated at 29&#46;52 &#91;27&#46;82&#8722;31&#46;32&#93;&#46; After one year and after 5 years&#44; 30&#37; and 78&#37; respectively discontinued treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In fact&#44; 50&#37; of patients discontinued treatment at 2&#46; &#91;1&#44;9&#8211;2&#44;3&#93; years from the start of the same&#46; According to the causes of discontinuation&#44; the highest incidence was AE&#44; followed by inefficacy&#44; the patient&#8217;s decision and the physician&#8217;s decision&#46; With regard to the sociodemographic characteristics&#44; the incidence was higher in women and in patients under 46 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; A 20&#37; loss of follow-up was recorded&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> presents the rates of discontinuation analysed according to treatment&#44; and we can see that the bDMARDs rate of discontinuation is almost double that of the sDMARDs&#44; with no major differences between the large groups of biologic agents &#40;anti-TNF or other biologics&#41;&#46; Regarding drug combinations&#44; the rate of discontinuation is over double in combined therapies compared with monotherapy&#44; especially when the combination is of 4 or more drugs&#46; The discontinuations were analysed according to the course of treatment&#44; with the posterior course being higher compared with the first one&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Lastly&#44; discontinuation rates were presented for each drug individually&#46; Among the sDMARDs gold salts&#44; sulfasalazine and leflunomide stand out as those which show a higher rate of discontinuation&#59; among the bDMARDs adalimumab followed by certolizumab were those presenting a higher rate of discontinuation&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">This study helps to increase our knowledge about managing daily life conditions in recent onset RA patients&#44; describing the causes of discontinuation of the different DMARDS used&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our cohort includes 814 patients with recent onset RA and maximum follow-up o f10 years&#46; Most patients were women with a mean age at disease onset of 57 years and over half of them were currently employed&#46; The diagnosis was established in almost three quarters of patients at the first visit and over half presented with a seropositive RA with higher disuse activity&#46; The most common comorbidities were high blood pressure and hypercholesterolemia&#46; Our cohort may be considered representative of the early onset RA population&#44; being comparable to other publications regarding sociodemographic and clinical characteristics&#46; The Scottish SERA<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> is analogous&#44; although its patients had a higher frequency of seropositivity and lower disease activity at the beginning&#59; the English is NORFOLK&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> was very similar to ours but seropositivity was lower as was disease activity and more time passed until the beginning of the first DMARD&#59; and the Canadian multicentre CATCH<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and French ESPOIR<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> were very similar to ours except their patients were slightly younger&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding the management of our patients&#44; treatment with DMARDs was initiated early&#44; less than one month after the establishment of the diagnosis of RA&#46; The start of treatment was made preferably in monotherapy with sDMARDs&#44; with oral methotrexate being the most widely used drug both in mono and in combined therapy&#44; and the most used of the bDMARDs being etanercept followed by adalimumab&#46; Combined therapy was used in 40&#37; of the courses of treatment&#44; particularly dual treatment and bDMARDs were used in 13&#37; of them&#46; Regarding the most frequently used drug combinations overall&#44; sDMARDs most used were methotrexate-hydroxychloroquine and sDMARDs with bDMARDs most used were methotrexate-adalimumab&#46; In triple therapy&#44; in synthetics the preferred was methotrexate-hydroxychloroquine-leflunomide and in sDMARDs with bDMARDs it was methotrexate-leflunomide-etanercept&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In the first course of treatment most patients received monotherapy with sDMARDs&#44; and of these the most used was methotrexate&#46; Combined therapy was used in under 10&#37; of patients and when it was used it was essentially dual therapy with sDMARDs&#44; mainly methotrexate-antimalarial&#46; In a few cases therapy with bDMARDs was used in the first course and when this was done the most used drug was etanercept&#46; In subsequent courses the most used drug in monotherapy was still methotrexate&#44; but the use of combined therapy increased considerably reaching up to over half of patients&#44; particularly in dual therapy&#46; In combined therapy again methotrexate-anti-malarials were still the most common&#59; with regard to bDMARDs the most common combination was methotrexate-adalimumab&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In all previously published cohorts&#44; the most used DMARD is methotrexate&#44; as in our cohort with a very similar use of bDMARDs to ours<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;18</span></a> and maybe a little higher in the French one&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> Regarding combined therapy&#44; the French cohort was outstanding<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> where it was used with much greater frequency&#46; Regarding biologics&#44; the most used were also adalimumab and etanercept&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">One thousand and ninety four discontinuations were recorded in 2388 courses of treatment&#44; with the main cause of discontinuation being the development of an AE&#44; followed by inefficacy&#46; These results coincide globally with previously published data&#46; Of note are the reports of bDMARDs LORHEN<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and SCQM-RA<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and the single centre cohort studies of Flendrie et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and Le&#243;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> since in them over half of discontinuations were also due to AE with inefficacy ranking second&#46; In the DANBIO and DREAM<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> reports&#44; the main cause of discontinuation is inefficacy followed by AE&#46; It should be considered that these are national reports of patients with established RA who receive anti-TNF with results published early &#40;the 6 first months of treatment in DANBIO<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and the first year in DREAM<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#41;&#46; Lastly&#44; the data published by the national registers of bDMARD in rheumatic diseases in Portugal&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Spain<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and Italy<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> were analysed&#46; Analysis of the data referring to RA revealed that the main cause of discontinuation was inefficacy&#44; followed by AE&#46; Regarding non anti-TNF bDMARDS&#44; there are fewer data available for these drugs since their marketing came after that of the anti-TNF drugs&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The main limitation of this study is its retrospective design&#44; which entails the existence of lost data&#46; Furthermore&#44; it is of note that the number of patients who received the newest bDMARDs &#40;tocilizumab or abatacept&#41; was lower than that of those who received the other drugs&#44; due to their later availability on the market&#46; However&#44; the great strength of this study is its inclusion of a wide number of recent onset RA patients who were followed up long term&#44; and this provided fortitude to the results&#46; Also&#44; this study was conducted in real life conditions with patients who were not selected from a single centre&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">To conclude&#44; we describe a cohort representative of early onset RA&#44; followed up for 10 years&#44; in which disease management was made in keeping with standards&#44; achieving a rapid diagnosis and establishing early and aggressive treatment with DMARDs&#46; With regard to the persistence of the sDMARDs&#44; we show that almost 30&#47;100 patients per year discontinued one or some of these drugs&#44; with mean administration of 2 years&#44; and we corroborated that most discontinuation was due to AE&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">These long-term&#44; real life&#44; longitudinal studies provide highly useful information for daily practice&#46; It would be very interesting to complete these cohorts in a few years time with further details on the new biologics &#40;rituximab&#44; abatacept y tocilizumab&#41; and the JAK-Kinase inhibitors&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Financing</span><p id="par0170" class="elsevierStylePara elsevierViewall">This study was conducted with support from the <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de Salud Carlos III&#44; Ministry of Health</span> &#91;Miguel Servet research contract&#58; CP11&#47;00189 of Lydia Ab&#225;solo&#59; health Investigation Fund&#58; <span class="elsevierStyleGrantNumber" refid="gs0005">PI18&#47;01188</span>&#59; <span class="elsevierStyleGrantSponsor" id="gs0010">Research Network in Inflammation and Rheumatic Diseases</span>&#58; RD16&#47;0012&#47;0014&#93; and <span class="elsevierStyleGrantSponsor" id="gs0015">Sanofi-Aventis&#44; S&#46;A</span>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interests</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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          "titulo" => "Results"
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          "titulo" => "Discussion"
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          "titulo" => "Financing"
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          "titulo" => "Conflict of interests"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-12-28"
    "fechaAceptado" => "2020-08-17"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1480667"
          "palabras" => array:3 [
            0 => "Early rheumatoid arthritis"
            1 => "Treatment discontinuation"
            2 => "Disease-modifying antirheumatic drugs"
          ]
        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1480666"
          "palabras" => array:3 [
            0 => "Artritis reumatoide temprana"
            1 => "Interrupci&#243;n del tratamiento"
            2 => "F&#225;rmacos antirreum&#225;ticos modificadores de la enfermedad"
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The treatment of Rheumatoid Arthritis &#40;RA&#41; has changed dramatically in recent years&#44; especially with the use of disease modifying drugs &#40;DMARDs&#41;&#46; Data on the management of this disease in clinical trials are abundant&#44; but not so in real life&#46; The aim of our study is to describe the management of an early RA cohort in daily clinical practice&#44; especially DMARD discontinuations and reasons&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A retrospective observational study of patients with RA diagnosed between 01&#47;07 and 12&#47;14 followed up to 01&#47;17&#44; using &#62;1 DMARD&#8239;&#8805;&#8239;3 months&#46; Variables&#58; sociodemographic&#44; clinical&#44; treatment&#44; DMARD discontinuation and reason&#46; Descriptive analysis of sociodemographic&#44; clinical and treatment characteristics&#46; Discontinuation incidence rate &#40;DIR&#41; due to survival techniques&#44; expressed in 100 patients&#42;year with 95&#37; confidence interval&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">814 patients were included with 2388 courses of treatment&#44; 77&#37; women&#44; mean age 57&#46;5 years&#46; First course&#58; monotherapy &#40;92&#46;75&#37;&#41;&#44; especially Methotrexate &#40;56&#46;06&#37;&#41;&#46; In later courses there was increased combined therapy and use of biologicals &#40;mainly Etanercept&#41;&#46; There were 1094 discontinuations &#40;29&#46;5 &#91;27&#46;8&#8211;31&#46;3&#93;&#41;&#46; The DIR was higher for adverse events &#40;15&#46;9 &#91;14&#46;7&#8211;17&#46;3&#93;&#41;&#44; biologicals &#40;49&#46;6 &#91;43&#46;1&#8211;57&#46;2&#93;&#41; and combined therapy&#46; The DMAR with the lowest DIR was MTX &#40;25&#46;8 &#91;23&#46;8&#8211;28&#46;1&#93;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Methotrexate was the most used drug&#44; biologicals increased throughout the follow-up&#44; the most frequent being Etanercept&#46; The DMARD DIR was 29&#42;100 patients per year&#44; mainly due to adverse events&#46; It seems to be higher in the therapies that include biologicals and combined therapies&#46; MTX is the drug with the lowest DIR&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "titulo" => "Conclusion"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El tratamiento de la Artritis Reumatoide &#40;AR&#41; ha cambiado dr&#225;sticamente en los &#250;ltimos a&#241;os&#44; sobre todo con el uso de los f&#225;rmacos modificadores de la enfermedad &#40;FAME&#41;&#46; Los datos sobre el manejo de esta enfermedad en ensayo cl&#237;nico son abundantes&#44; pero no en la vida real&#46; El objetivo de nuestro estudio es describir el manejo de una cohorte de AR de inicio en pr&#225;ctica cl&#237;nica diaria&#44; especialmente las suspensiones de los FAME y sus causas&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional retrospectivo de pacientes con AR diagnosticados entre 01&#47;07 y 12&#47;14 seguidos hasta 01&#47;17&#44; que usaron &#62;1 FAME&#8239;&#8805;&#8239;3 meses&#46; Variables&#58; sociodemogr&#225;ficas&#44; cl&#237;nicas&#44; tratamiento&#44; suspensi&#243;n del FAME y causa&#46; An&#225;lisis descriptivo de las caracter&#237;sticas sociodemogr&#225;ficas&#44; cl&#237;nicas y de tratamiento&#46; Incidencia de suspensi&#243;n &#40;IS&#41; por t&#233;cnicas de supervivencia&#44; expres&#225;ndose en 100 pacientes&#42;a&#241;o con intervalo de confianza 95&#37;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Se incluyen 814 pacientes con 2388 cursos de tratamiento&#44; 77&#37; mujeres&#44; edad media 57&#44;5 a&#241;os&#46; Primer curso&#58; monoterapia &#40;92&#44;75&#37;&#41;&#44; especialmente Metotrexate &#40;56&#44;06&#37;&#41;&#46; En posteriores cursos aumentan terapia combinada y uso de biol&#243;gico &#40;principalmente Etanercept&#41;&#46; Se registraron 1094 suspensiones &#40;29&#44;5&#91;27&#44;8&#8211;31&#44;3&#93;&#41;&#46; La IS fue mayor para evento adverso &#40;15&#44;9&#91;14&#44;7&#8211;17&#44;3&#93;&#41;&#44; biol&#243;gicos &#40;49&#44;6&#91;43&#44;1&#8211;57&#44;2&#93;&#41; y terapia combinada&#46; El FAME con menor IS fue MTX &#40;25&#44;8&#91;23&#44;8&#8211;28&#44;1&#93;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">El Metotrexate fue el f&#225;rmaco m&#225;s utilizado&#44; el biol&#243;gico aument&#243; a lo largo del seguimiento&#44; siendo el m&#225;s frecuente Etanercept&#46; La IS de los FAME fue 29&#42;100 pacientes a&#241;o&#44; principalmente por evento adverso&#46; Parece mayor en las terapias que incluyen biol&#243;gicos y en las combinadas&#46; El MTX es el f&#225;rmaco con menor IS&#46;</p></span>"
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            "titulo" => "Resultados"
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            "titulo" => "Conclusi&#243;n"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rosales Rosado Z&#44; Font Urgelles J&#44; Hern&#225;ndez Rodr&#237;guez I&#44; Le&#243;n Mateos L&#44; Ab&#225;solo Alc&#225;zar L&#44; Jover Jover J&#193;&#46; Manejo cl&#237;nico y discontinuaci&#243;n de tratamiento en pacientes con artritis reumatoide de inicio en una consulta de Reumatolog&#237;a&#46; Reumatol Clin&#46; 2022&#59;18&#58;77&#8211;83&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Most commonly used drug combinations&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Anti-CCP&#58; anti-citrullinated peptide&#59; DAS&#58; disease activity score&#59; ESR&#58; erythrocyte sedimentation rate&#59; SD&#58; standard deviation&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total patients &#40;n&#8239;&#61;&#8239;814&#41;</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">631&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">77&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Civil status &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">562&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">356&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">63&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">217&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">43&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Manual&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">185&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">43&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">424&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">52&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Lives with &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">598&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Family&#47;colleagues&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">511&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T<span class="elsevierStyleItalic">ime</span><span class="elsevierStyleItalic">until diagnosis&#44; months</span> &#8239;<span class="elsevierStyleItalic">&#177;</span>&#8239;<span class="elsevierStyleItalic">SD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t">8&#46;81&#8239;&#177;&#8239;226&#46;25</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">593&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tobacco &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">719&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never a smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Positive rheumatoid factor &#40;n&#8239;&#61;&#8239;810&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Anti-CCP positive antibodies &#40;n&#8239;&#61;&#8239;792&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ESR on diagnosis&#44; mm&#47;h</span>&#8239;<span class="elsevierStyleItalic">&#177;</span>&#8239;<span class="elsevierStyleItalic">SD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#46;62&#8239;&#177;&#8239;28&#46;14</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">DAS 28-VSG on diagnosis</span>&#8239;<span class="elsevierStyleItalic">&#177;</span>&#8239;<span class="elsevierStyleItalic">SD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;26&#8239;&#177;&#8239;1&#46;44</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Rosser index on diagnosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;97&#8239;&#177;&#8239;&#46;04</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Baseline comorbidity</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypercholesterolaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">251&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ischaemic cardiopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cerebrovascular pathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Peripheral artery disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastric ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chronic obstructive pulmonary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Liver disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Kidney failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cognitive impairment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Global &#40;n&#8239;&#61;&#8239;2388&#41;</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t">59&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combined&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">40&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chloroquine&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Leflunomide&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Oral methotrexate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1257&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">52&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subcutaneous methotrexate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gold salts&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">5&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abatacept&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adalimumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Certolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Type of drug</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Non biologic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2062&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Monotherapy with non biologic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1372&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combined with non biologic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">690&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Monotherapy with anti-TNF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combined with anti-TNF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Monotherapy with other biologic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combined with other biologic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;85&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">People&#47;year&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1094&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">29&#46;52&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">27&#46;82&#8722;31&#46;32&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Woman&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">297&#44;678&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">900&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#44;936&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">194&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">26&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;11&#8722;30&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">By age on diagnosis</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;46 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">319&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;47&#8722;39&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>46&#8211;70 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">196&#44;368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;32&#8722;29&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">14&#46;55&#8722;17&#46;08&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Decision by the physician&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">124&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Decision by the patient&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">116&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Improvement&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">1&#46;39&#8722;2&#46;26&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;11&#8722;1&#46;90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25&#46;46&#8722;29&#46;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Biologic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-TNF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39&#46;52&#8722;69&#46;58&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">509&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46;91&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">585&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46&#46;92&#8722;55&#46;18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">By number of DMARDS</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">509&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">435&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&#46;41&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">191&#46;85&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">150&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">78&#46;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">66&#46;62&#8722;91&#46;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">By course of treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">325&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46;50&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&#46;50&#8722;21&#46;74&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Subsequent</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">769&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37&#46;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&#46;13&#8722;40&#46;46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">synthetic DMARDS</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Chloroquine</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">684&#46;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">269&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39&#46;30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34&#46;87&#8722;44&#46;29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hydroxychloroquine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">626&#46;88&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">239&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38&#46;13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33&#46;59&#8722;43&#46;28&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Leflunomide</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">482&#46;83&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">238&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">4929&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">62&#46;30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tocilizumab</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;45&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;14&#8722;127&#46;57&nbsp;\t\t\t\t\t\t\n
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                  """
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                0 => "xTab2837043.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Rates of discontinuation according to treatment&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
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Original Article
Clinical management and discontinuation of treatment in patients with recent onset rheumatoid arthritis in a rheumatology consultation
Manejo clínico y discontinuación de tratamiento en pacientes con artritis reumatoide de inicio en una consulta de Reumatología
Zulema Rosales Rosadoa,
Corresponding author
zulema.rosales@salud.madrid.org

Corresponding author.
, Judit Font Urgellesb, Isabel Hernández Rodrígueza, Leticia León Mateosb, Lydia Abásolo Alcázarb, Juan Ángel Jover Jovera
a Servicio de Reumatología, Hospital Clínico San Carlos, Madrid, Spain
b Instituto de Investigación Sanitaria San Carlos, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a chronic autoimmune disease which basically affects peripheral joints symmetrically&#44; leading to inflammation&#44; progressive destruction and bone erosion<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#59; it is also associated with systemic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It also leads to deterioration of functional capacity&#44; occupational disability&#44; reduction of quality of life and increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Its prevalence ranges from between &#46;5&#37;-1&#37; of the population&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The appearance of joint damage is particularly fast at disease onset&#44; suggesting that there is a &#8220;window of opportunity&#8221; at this stage&#44; referring to the first few months since onset&#44; when the patient is considered most likely to respond to treatment than in more advanced stages&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Due to this&#44; early diagnosis and treatment is essential&#44; thereby increasing the possibility of controlling the inflammation and reducing damage&#46; As a result&#44; RA management and prognosis have drastically changed in recent years&#46; The main objectives is to achieve complete remission or at least a low stable activity&#44; improving functional prognosis of the patient by employing a treat to target strategy&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Also&#44; during management we must not forget pain control&#44; and the reduction of corticosteroids or preferably their discontinuation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Current therapeutic strategies include treatments aimed at fast pain and inflammation control and disease-modifying anti-rheumatic drugs &#40;DMARDs&#41; which may be synthetic &#40;sDMARDs&#41; or biologic &#40;bDMARDs&#41; &#40;anti-TNF&#44; other biologics and new targeted therapies&#41;&#46; Their use should be introduced as soon as possible during the course of the disease&#44; in full doses&#44; alone or in combination so as to increase the therapeutic efficacy covered by the treat to target strategy&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The lack of standardised forms of different treatment usage has lead to different combinations being used&#46; These depend both on the physician and the availability of the drugs as well as the individual characteristics of each patient&#46; The change in therapeutic objectives and the broadening of treatment options have determined multiple possibilities for patient management in daily clinical practice&#46; Clinical trial data abound in the literature<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> but not in real life&#46; As a result&#44; our aim was to obtain clinical practice information regarding recent onset RA&#46; We will describe the clinical management and treatment&#44; its persistence&#44; and the reasons for discontinuation in a cohort of patients with recent onset RA in conditions of daily clinical practice followed up in an outpatient rheumatology unit consultation of a tertiary hospital&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0025" class="elsevierStylePara elsevierViewall">A retrospective&#44; longitudinal&#44; observational study&#46; It included patients diagnosed with RA between 01&#47;01&#47;07 and 31&#47;12&#47;14&#46; Follow-up included up to the loss of follow-up or the end of the study &#40;01&#47;01&#47;17&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Scope of the study</span><p id="par0030" class="elsevierStylePara elsevierViewall">Rheumatology Unit of the Hospital Cl&#237;nico San Carlos&#44; which is a tertiary public hospital with a catchment area serving approximately 600&#44;000 people&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Subjects</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients over 16 diagnosed with RA were included &#40;ACR&#47;EULAR 2010 criteria&#41;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> less than one year prior to inclusion&#46; To enter into the study it was necessary for the patient to sign the informed consent form&#44; have completed at least 2 visits to the rheumatology unit and to have received at least one sDMARD &#40;chloroquine&#44; hydroxychloroquine&#44; methotrexate&#44; leflunomide&#44; gold injections&#44; sulfasalazine&#44; cyclosporine&#44; cyslophosphamide&#44; azathioprine&#44; mycophenolate mofetil&#41; or a bDMARD &#40;infliximab&#44; adalimumab&#44; etanercept&#44; golimumab&#44; certolizumab pegol&#44; rituximab&#44; abatacept&#44; tocilizumab&#41; during the inclusion period&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This study was approved by the ethics and institutional clinical trial committee of the Hospital Cl&#237;nico San Carlos&#46; Also&#44; according to their indications&#44; it referred to the Spanish Medicine Agency&#44; which classified it as an observational study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data sources</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patient data were collected through the departmental electronic clinical records of the rheumatology unit of the Hospital Clinic San Carlos where routine visits were recorded in &#8220;real time&#8221;&#46; Furthermore&#44; written clinical files were reviewed to complete data which was lacking&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Variables</span><p id="par0050" class="elsevierStylePara elsevierViewall">1&#41; Sociodemographic&#58; age&#44; sex&#44; civil status&#44; level of education&#44; category&#44; employment situation and residential situation &#40;alone&#44; family&#47;friends&#44; institutionalised&#41;&#46; 2&#41; Clinical&#58; a&#41; date of diagnosis&#44; b&#41; smoker&#44; c&#41; baseline quality of life measured by the Rosser index&#44; d&#41; analytics&#58; baseline sedimentation rate&#44; rheumatoid factor&#44; anti-citrullinated peptide antibodies&#44; e&#41; baseline disease activity measured through the HAQ and DAS 28&#46; 3&#41; Baseline comorbidity&#58; high blood pressure&#44; diabetes mellitus&#44; hypercholesterolaemia&#44; ischaemic cardiopathy&#44; congestive heart failure&#44; cerebrovascular pathology&#44; peripheral artery disease&#44; cancer and type of cancer&#44; depression&#44; gastroduodenal ulcer&#44; chronic obstructive pulmonary disease&#44; liver disease&#44; osteoporosis&#44; fractures&#44; kidney failure&#44; cognitive impairment and thyroid alterations&#46; 4&#41; sDMARDs&#58; type &#40;chloroquine&#44; hydroxychloroquine&#44; methotrexate&#44; leflunomide&#44; gold salts&#44; sulfasalazine&#44; cyclosporine&#44; cyslophosphamide&#44; azathioprine&#44; mycophenolate mofetil&#41;&#44; start and finish dates&#46; 5&#41; bDMARDs&#58; type &#40;infliximab&#44; adalimumab&#44; etanercept&#44; golimumab&#44; certolizumab pegol&#44; rituximab&#44; abatacept&#44; tocilizumab&#41;&#44; start and finish dates&#46; 6&#41; Concomitant treatments &#40;if they have been used for at least 3 months since the beginning of each treatment course with sDMARDs&#41;&#58; a&#41; use of opioids and anti-inflammatory analgesics&#44; b&#41; mean corticoid dose&#46; 7&#41; reasons for suspension of sDMARDs&#58; a&#41; adverse event &#40;AE&#41;&#58; the type&#44; severity and relationship with the drug were recorded b&#41; inefficacy&#44; c&#41; patient&#8217;s decision&#44; e&#41; physician&#8217;s decision&#44; f&#41; remission or improvement defined by the criterion of the rheumatologist responsible for the patient&#44; g&#41; others &#40;including the desire for children or the suspension of programmed surgery for over 3 months&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">A descriptive analysis was performed of the subjects with sociodemographic and clinical characteristics&#44; treatments with tns DMARDs &#40;first and second line&#41;&#44; in monotherapy or combined therapies over time&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The reasons for discontinuation were described using frequencies&#44; mean and standard deviation&#44; medians or percentiles&#46; The persistence of treatment and the incidence of suspension were assessed using survival techniques&#44; expressed by100 patients&#47;year with a 95&#37; confidence interval&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All analysis was performed with the statistical programme Stata v&#46;13 <span class="elsevierStyleItalic">Special Edition&#8211;Statistics&#47;Data Analysis</span>&#46; A two-tailed <span class="elsevierStyleItalic">P</span> value under &#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Eight hundred and fourteen patients were included&#44; with a mean follow-up of 5 years &#40;median&#58; 5&#46;1 &#91;p25&#8722;75&#58; 2&#46;97&#8211;7&#46;12&#93;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> contains the sociodemographic and baseline clinical characteristics&#46; Over three quarters of the patients were women &#40;77&#46;52&#37;&#41; with a mean age at diagnosis of 57&#46;53 &#40;&#177;15&#46;50 years&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Mean time up to diagnosis was 8&#46;81 months &#40;&#177;226&#46;25&#41;&#44; achieving a diagnosis during the first visit in 72&#46;85&#37; of patients&#46; A higher percentage of patients were recorded who had never smoked compared with active or ex-smokers&#46; Approximately half of the patents presented with seropositive RA&#46; Regarding disease activity on diagnosis&#44; the median erythrocyte sedimentation rate was 42&#46;62 &#40;&#177;28&#46;14&#41; mm&#47;h and <span class="elsevierStyleItalic">DAS 28</span> mean was 5&#46;26&#8239;&#177;&#8239;1&#46;44&#46; Regarding measurement of quality of life using the Rosser index n diagnosis&#44; a mean of &#46;97&#8239;&#177;&#8239;&#46;04 was obtained&#46; Regarding comorbidity&#44; both blood pressure and hypercholesterolaemia were the most prevalent pathologies to be detected in over a third of patients on diagnosis&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Two thousand&#44; three hundred and eighty eight courses of treatment with DMARDs were registered in the 814 patients&#44; with mean time up until the first line of treatment at 21 &#91;0&#8211;43&#93; days&#46; The most commonly used drug was oral methotrexate followed by anti-malarial drugs &#40;see <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Combined therapy in our cohort was used in 40&#46;08&#37; &#40;dual therapy in 31&#46;87&#37;&#59; &#8805;3 drugs in 8&#46;25&#37;&#41; and biologics were used in 13&#46;65&#37; of treatments&#44; both as monotherapy and combined&#46; Regarding the way in which the DMARDs were used&#44; the most common was immunotherapy of sDMARDs &#40;57&#46;45&#37;&#41; followed by combined therapy of sDMARDs &#40;28&#46;89&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Concomitant treatments used were also collected&#46; In 83&#46;75&#37; of treatments these were associated with corticoids with a mean dose of 1&#46;20 &#40;&#177;&#8239;&#46;77&#41;&#8239;mg&#46; In 36&#46;06&#37; of treatments the concomitant use of non-steroid anti-inflammatory was recorded whilst that of opioids was much lower &#40;minor opioids 6&#46;74&#37; of courses&#59; major opioids 5&#46;65&#37; of courses&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">An analysis of drug combinations most commonly used was performed and we observed that the most used sDMARDs in monotherapy was methotrexate and in bDMARDs was etanercept&#59; regarding combined therapy&#44; in dual therapy the preferred combination of sDMARDs was methotrexate and hydroxychloroquine and that of sDMARDs with bDMARDs was methotrexate and adalimumab&#46; Regarding triple therapy&#44; in synthetics the preferred was methotrexate with hydroxychloroquine and leflunomide and in sDMARDs with bDMARDs was methotrexate with leflunomide and etanercept&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">This same analysis was repeated by course of treatment&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the first course of treatment&#46; During the first course&#44; monotherapy was most commonly used&#44; and within it&#44; monotherapy with sDMARDs&#44; especially methotrexate&#59; 4 cases of monotherapy with bDMARDs were recorded&#46; Regarding combined therapy&#44; in the first course of treatment&#44; its use was very low and was essentially given as dual&#44; or occasionally as triple therapy&#46; sDMARDs were almost always used&#59; a single case of a combination of sDMARDs and bDMARDs as the first course of treatment was recorded&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">In later courses of treatment we were able to appreciate several differences&#46; Regarding monotherapy&#44; the most used sDMARD was also methotrexate &#40;41&#46;22&#37;&#41; but there were differences in the bDMARDs&#44; since etanercept and adalimumab &#40;20&#37; both&#41; were used equally&#46; Combined therapy was used with greater frequency &#40;57&#46;05&#37;&#41;&#44; and within it dual therapy was particularly used &#40;78&#46;51&#37;&#41;&#46; In dual therapy essentially sDMARDs were used with methotrexate-hydroxychloroquine being the most used combination &#40;22&#46;18&#37;&#41; followed by methotrexate-chloroquine &#40;20&#46;93&#37;&#41;&#59; within dual therapy with biologics there was a more frequent use of methotrexate-adalimumab &#40;13&#46;70&#37;&#41; followed by leflunomide-etanercept &#40;9&#46;59&#37;&#41;&#46; Regarding triple therapy &#40;21&#46;49&#37;&#41;&#44; which was most frequently used as a combination of bDMARDs &#40;62&#46;18&#37;&#41;&#44; the most used was methotrexate-leflunomide-etanercept &#40;6&#46;67&#37;&#41;&#59; when triple therapy with sDMARDs was chosen&#44; the most used was the combination of methotrexate-leflunomide-hydroxychloroquine &#40;15&#46;07&#37;&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Discontinuations of 1094 of the 2388 courses of treatment were recorded in 361 patients&#44; 150 due to inefficacy in 110 patients&#44; 124 due to the physician&#8217;s decision in 102 patients&#44; 66 due to improvement in 61 patients&#44; 116 due to the patient&#8217;s decision in 103 patients and 54 due to other causes in 51 patients&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The incidence of discontinuation in our cohort was estimated at 29&#46;52 &#91;27&#46;82&#8722;31&#46;32&#93;&#46; After one year and after 5 years&#44; 30&#37; and 78&#37; respectively discontinued treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In fact&#44; 50&#37; of patients discontinued treatment at 2&#46; &#91;1&#44;9&#8211;2&#44;3&#93; years from the start of the same&#46; According to the causes of discontinuation&#44; the highest incidence was AE&#44; followed by inefficacy&#44; the patient&#8217;s decision and the physician&#8217;s decision&#46; With regard to the sociodemographic characteristics&#44; the incidence was higher in women and in patients under 46 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; A 20&#37; loss of follow-up was recorded&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> presents the rates of discontinuation analysed according to treatment&#44; and we can see that the bDMARDs rate of discontinuation is almost double that of the sDMARDs&#44; with no major differences between the large groups of biologic agents &#40;anti-TNF or other biologics&#41;&#46; Regarding drug combinations&#44; the rate of discontinuation is over double in combined therapies compared with monotherapy&#44; especially when the combination is of 4 or more drugs&#46; The discontinuations were analysed according to the course of treatment&#44; with the posterior course being higher compared with the first one&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Lastly&#44; discontinuation rates were presented for each drug individually&#46; Among the sDMARDs gold salts&#44; sulfasalazine and leflunomide stand out as those which show a higher rate of discontinuation&#59; among the bDMARDs adalimumab followed by certolizumab were those presenting a higher rate of discontinuation&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">This study helps to increase our knowledge about managing daily life conditions in recent onset RA patients&#44; describing the causes of discontinuation of the different DMARDS used&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Our cohort includes 814 patients with recent onset RA and maximum follow-up o f10 years&#46; Most patients were women with a mean age at disease onset of 57 years and over half of them were currently employed&#46; The diagnosis was established in almost three quarters of patients at the first visit and over half presented with a seropositive RA with higher disuse activity&#46; The most common comorbidities were high blood pressure and hypercholesterolemia&#46; Our cohort may be considered representative of the early onset RA population&#44; being comparable to other publications regarding sociodemographic and clinical characteristics&#46; The Scottish SERA<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> is analogous&#44; although its patients had a higher frequency of seropositivity and lower disease activity at the beginning&#59; the English is NORFOLK&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> was very similar to ours but seropositivity was lower as was disease activity and more time passed until the beginning of the first DMARD&#59; and the Canadian multicentre CATCH<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and French ESPOIR<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> were very similar to ours except their patients were slightly younger&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding the management of our patients&#44; treatment with DMARDs was initiated early&#44; less than one month after the establishment of the diagnosis of RA&#46; The start of treatment was made preferably in monotherapy with sDMARDs&#44; with oral methotrexate being the most widely used drug both in mono and in combined therapy&#44; and the most used of the bDMARDs being etanercept followed by adalimumab&#46; Combined therapy was used in 40&#37; of the courses of treatment&#44; particularly dual treatment and bDMARDs were used in 13&#37; of them&#46; Regarding the most frequently used drug combinations overall&#44; sDMARDs most used were methotrexate-hydroxychloroquine and sDMARDs with bDMARDs most used were methotrexate-adalimumab&#46; In triple therapy&#44; in synthetics the preferred was methotrexate-hydroxychloroquine-leflunomide and in sDMARDs with bDMARDs it was methotrexate-leflunomide-etanercept&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In the first course of treatment most patients received monotherapy with sDMARDs&#44; and of these the most used was methotrexate&#46; Combined therapy was used in under 10&#37; of patients and when it was used it was essentially dual therapy with sDMARDs&#44; mainly methotrexate-antimalarial&#46; In a few cases therapy with bDMARDs was used in the first course and when this was done the most used drug was etanercept&#46; In subsequent courses the most used drug in monotherapy was still methotrexate&#44; but the use of combined therapy increased considerably reaching up to over half of patients&#44; particularly in dual therapy&#46; In combined therapy again methotrexate-anti-malarials were still the most common&#59; with regard to bDMARDs the most common combination was methotrexate-adalimumab&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In all previously published cohorts&#44; the most used DMARD is methotrexate&#44; as in our cohort with a very similar use of bDMARDs to ours<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;18</span></a> and maybe a little higher in the French one&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> Regarding combined therapy&#44; the French cohort was outstanding<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> where it was used with much greater frequency&#46; Regarding biologics&#44; the most used were also adalimumab and etanercept&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">One thousand and ninety four discontinuations were recorded in 2388 courses of treatment&#44; with the main cause of discontinuation being the development of an AE&#44; followed by inefficacy&#46; These results coincide globally with previously published data&#46; Of note are the reports of bDMARDs LORHEN<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and SCQM-RA<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and the single centre cohort studies of Flendrie et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and Le&#243;n et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> since in them over half of discontinuations were also due to AE with inefficacy ranking second&#46; In the DANBIO and DREAM<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> reports&#44; the main cause of discontinuation is inefficacy followed by AE&#46; It should be considered that these are national reports of patients with established RA who receive anti-TNF with results published early &#40;the 6 first months of treatment in DANBIO<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and the first year in DREAM<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#41;&#46; Lastly&#44; the data published by the national registers of bDMARD in rheumatic diseases in Portugal&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Spain<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and Italy<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> were analysed&#46; Analysis of the data referring to RA revealed that the main cause of discontinuation was inefficacy&#44; followed by AE&#46; Regarding non anti-TNF bDMARDS&#44; there are fewer data available for these drugs since their marketing came after that of the anti-TNF drugs&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The main limitation of this study is its retrospective design&#44; which entails the existence of lost data&#46; Furthermore&#44; it is of note that the number of patients who received the newest bDMARDs &#40;tocilizumab or abatacept&#41; was lower than that of those who received the other drugs&#44; due to their later availability on the market&#46; However&#44; the great strength of this study is its inclusion of a wide number of recent onset RA patients who were followed up long term&#44; and this provided fortitude to the results&#46; Also&#44; this study was conducted in real life conditions with patients who were not selected from a single centre&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">To conclude&#44; we describe a cohort representative of early onset RA&#44; followed up for 10 years&#44; in which disease management was made in keeping with standards&#44; achieving a rapid diagnosis and establishing early and aggressive treatment with DMARDs&#46; With regard to the persistence of the sDMARDs&#44; we show that almost 30&#47;100 patients per year discontinued one or some of these drugs&#44; with mean administration of 2 years&#44; and we corroborated that most discontinuation was due to AE&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">These long-term&#44; real life&#44; longitudinal studies provide highly useful information for daily practice&#46; It would be very interesting to complete these cohorts in a few years time with further details on the new biologics &#40;rituximab&#44; abatacept y tocilizumab&#41; and the JAK-Kinase inhibitors&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Financing</span><p id="par0170" class="elsevierStylePara elsevierViewall">This study was conducted with support from the <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de Salud Carlos III&#44; Ministry of Health</span> &#91;Miguel Servet research contract&#58; CP11&#47;00189 of Lydia Ab&#225;solo&#59; health Investigation Fund&#58; <span class="elsevierStyleGrantNumber" refid="gs0005">PI18&#47;01188</span>&#59; <span class="elsevierStyleGrantSponsor" id="gs0010">Research Network in Inflammation and Rheumatic Diseases</span>&#58; RD16&#47;0012&#47;0014&#93; and <span class="elsevierStyleGrantSponsor" id="gs0015">Sanofi-Aventis&#44; S&#46;A</span>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interests</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2019-12-28"
    "fechaAceptado" => "2020-08-17"
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            0 => "Early rheumatoid arthritis"
            1 => "Treatment discontinuation"
            2 => "Disease-modifying antirheumatic drugs"
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            0 => "Artritis reumatoide temprana"
            1 => "Interrupci&#243;n del tratamiento"
            2 => "F&#225;rmacos antirreum&#225;ticos modificadores de la enfermedad"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The treatment of Rheumatoid Arthritis &#40;RA&#41; has changed dramatically in recent years&#44; especially with the use of disease modifying drugs &#40;DMARDs&#41;&#46; Data on the management of this disease in clinical trials are abundant&#44; but not so in real life&#46; The aim of our study is to describe the management of an early RA cohort in daily clinical practice&#44; especially DMARD discontinuations and reasons&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A retrospective observational study of patients with RA diagnosed between 01&#47;07 and 12&#47;14 followed up to 01&#47;17&#44; using &#62;1 DMARD&#8239;&#8805;&#8239;3 months&#46; Variables&#58; sociodemographic&#44; clinical&#44; treatment&#44; DMARD discontinuation and reason&#46; Descriptive analysis of sociodemographic&#44; clinical and treatment characteristics&#46; Discontinuation incidence rate &#40;DIR&#41; due to survival techniques&#44; expressed in 100 patients&#42;year with 95&#37; confidence interval&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">814 patients were included with 2388 courses of treatment&#44; 77&#37; women&#44; mean age 57&#46;5 years&#46; First course&#58; monotherapy &#40;92&#46;75&#37;&#41;&#44; especially Methotrexate &#40;56&#46;06&#37;&#41;&#46; In later courses there was increased combined therapy and use of biologicals &#40;mainly Etanercept&#41;&#46; There were 1094 discontinuations &#40;29&#46;5 &#91;27&#46;8&#8211;31&#46;3&#93;&#41;&#46; The DIR was higher for adverse events &#40;15&#46;9 &#91;14&#46;7&#8211;17&#46;3&#93;&#41;&#44; biologicals &#40;49&#46;6 &#91;43&#46;1&#8211;57&#46;2&#93;&#41; and combined therapy&#46; The DMAR with the lowest DIR was MTX &#40;25&#46;8 &#91;23&#46;8&#8211;28&#46;1&#93;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Methotrexate was the most used drug&#44; biologicals increased throughout the follow-up&#44; the most frequent being Etanercept&#46; The DMARD DIR was 29&#42;100 patients per year&#44; mainly due to adverse events&#46; It seems to be higher in the therapies that include biologicals and combined therapies&#46; MTX is the drug with the lowest DIR&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El tratamiento de la Artritis Reumatoide &#40;AR&#41; ha cambiado dr&#225;sticamente en los &#250;ltimos a&#241;os&#44; sobre todo con el uso de los f&#225;rmacos modificadores de la enfermedad &#40;FAME&#41;&#46; Los datos sobre el manejo de esta enfermedad en ensayo cl&#237;nico son abundantes&#44; pero no en la vida real&#46; El objetivo de nuestro estudio es describir el manejo de una cohorte de AR de inicio en pr&#225;ctica cl&#237;nica diaria&#44; especialmente las suspensiones de los FAME y sus causas&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional retrospectivo de pacientes con AR diagnosticados entre 01&#47;07 y 12&#47;14 seguidos hasta 01&#47;17&#44; que usaron &#62;1 FAME&#8239;&#8805;&#8239;3 meses&#46; Variables&#58; sociodemogr&#225;ficas&#44; cl&#237;nicas&#44; tratamiento&#44; suspensi&#243;n del FAME y causa&#46; An&#225;lisis descriptivo de las caracter&#237;sticas sociodemogr&#225;ficas&#44; cl&#237;nicas y de tratamiento&#46; Incidencia de suspensi&#243;n &#40;IS&#41; por t&#233;cnicas de supervivencia&#44; expres&#225;ndose en 100 pacientes&#42;a&#241;o con intervalo de confianza 95&#37;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Se incluyen 814 pacientes con 2388 cursos de tratamiento&#44; 77&#37; mujeres&#44; edad media 57&#44;5 a&#241;os&#46; Primer curso&#58; monoterapia &#40;92&#44;75&#37;&#41;&#44; especialmente Metotrexate &#40;56&#44;06&#37;&#41;&#46; En posteriores cursos aumentan terapia combinada y uso de biol&#243;gico &#40;principalmente Etanercept&#41;&#46; Se registraron 1094 suspensiones &#40;29&#44;5&#91;27&#44;8&#8211;31&#44;3&#93;&#41;&#46; La IS fue mayor para evento adverso &#40;15&#44;9&#91;14&#44;7&#8211;17&#44;3&#93;&#41;&#44; biol&#243;gicos &#40;49&#44;6&#91;43&#44;1&#8211;57&#44;2&#93;&#41; y terapia combinada&#46; El FAME con menor IS fue MTX &#40;25&#44;8&#91;23&#44;8&#8211;28&#44;1&#93;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">El Metotrexate fue el f&#225;rmaco m&#225;s utilizado&#44; el biol&#243;gico aument&#243; a lo largo del seguimiento&#44; siendo el m&#225;s frecuente Etanercept&#46; La IS de los FAME fue 29&#42;100 pacientes a&#241;o&#44; principalmente por evento adverso&#46; Parece mayor en las terapias que incluyen biol&#243;gicos y en las combinadas&#46; El MTX es el f&#225;rmaco con menor IS&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rosales Rosado Z&#44; Font Urgelles J&#44; Hern&#225;ndez Rodr&#237;guez I&#44; Le&#243;n Mateos L&#44; Ab&#225;solo Alc&#225;zar L&#44; Jover Jover J&#193;&#46; Manejo cl&#237;nico y discontinuaci&#243;n de tratamiento en pacientes con artritis reumatoide de inicio en una consulta de Reumatolog&#237;a&#46; Reumatol Clin&#46; 2022&#59;18&#58;77&#8211;83&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total patients &#40;n&#8239;&#61;&#8239;814&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Civil status &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">562&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">356&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">63&#46;35&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Level of education &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">494&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">217&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Manual&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Active&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">424&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Lives with &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">598&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Family&#47;colleagues&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">511&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T<span class="elsevierStyleItalic">ime</span><span class="elsevierStyleItalic">until diagnosis&#44; months</span> &#8239;<span class="elsevierStyleItalic">&#177;</span>&#8239;<span class="elsevierStyleItalic">SD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;81&#8239;&#177;&#8239;226&#46;25</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Diagnosis at first visit</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">593&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tobacco &#40;n</span>&#8239;<span class="elsevierStyleItalic">&#61;</span>&#8239;<span class="elsevierStyleItalic">719&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never a smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Positive rheumatoid factor &#40;n&#8239;&#61;&#8239;810&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Anti-CCP positive antibodies &#40;n&#8239;&#61;&#8239;792&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ESR on diagnosis&#44; mm&#47;h</span>&#8239;<span class="elsevierStyleItalic">&#177;</span>&#8239;<span class="elsevierStyleItalic">SD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#46;62&#8239;&#177;&#8239;28&#46;14</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">DAS 28-VSG on diagnosis</span>&#8239;<span class="elsevierStyleItalic">&#177;</span>&#8239;<span class="elsevierStyleItalic">SD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;26&#8239;&#177;&#8239;1&#46;44</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Rosser index on diagnosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;97&#8239;&#177;&#8239;&#46;04</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Baseline comorbidity</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High blood pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypercholesterolaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">251&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ischaemic cardiopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cerebrovascular pathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Peripheral artery disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastric ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chronic obstructive pulmonary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Liver disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Kidney failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cognitive impairment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Global &#40;n&#8239;&#61;&#8239;2388&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Number of DMARDs</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">814&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34&#46;09&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">532&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&#46;28&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">367&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&#8722;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">497&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">20&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">178&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Combined therapy</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Monotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1431&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">957&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Drugs</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chloroquine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">493&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hydroxychloroquine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">488&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Leflunomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">441&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Oral methotrexate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1257&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subcutaneous methotrexate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">206&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gold salts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sulfasalazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">202&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Azathioprine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abatacept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Certolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Type of drug</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Non biologic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2062&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-TNF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other biologics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">199&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;85&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">People&#47;year&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">29&#46;52&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">27&#46;82&#8722;31&#46;32&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Woman&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">900&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28&#46;32&#8722;32&#46;28&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Man&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;60&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;11&#8722;30&#46;62&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;46 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">319&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;47&#8722;39&#46;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>46&#8211;70 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">196&#44;368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">541&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;32&#8722;29&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;70 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#44;409&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;68&#8722;31&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">By cause of discontinuation</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adverse event&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">370&#44;614&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">584&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#46;55&#8722;17&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">By course of treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">47&#46;14&#8722;66&#46;85&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Biologic DMARDS</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">12&#46;68&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 21735743
Original language: English
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Idiomas
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