Editorial
Considerations on treatment recommendations for rheumatoid arthritis
Consideraciones a las recomendaciones terapéuticas para la artritis reumatoide
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In this quest, several guidelines have been published to reach this outcome. Some recommendations, however, may awaken a certain degree of dissent or provide food for thought, while yet other points of interest merit inclusion in these guidelines.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Periodical guideline evaluations have produced clarifications, such as, “monitoring should be frequent in active disease (every 1–3 months); if there is no improvement by at most 3 months after treatment start or the target has not been reached by 6 months, therapy should be adjusted.”<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is reasonable that adjustments in treatment may be done one month after treatment for those patients with poor prognostic factors,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> those with high disease activity score with triple therapy, and in cases of persistent or increased activity (number of painful and inflamed joints, elevated acute-phase reactants, positive serology, early radiological changes, extra-articular manifestations). Rheumatologists should make therapeutic modifications without waiting to reach wide-ranging limits to modify treatment, which is also applicable when there is expression of toxicity. Several studies have emphasized the advantages of achieving early remission, even for longer survival.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Despite this, most controlled studies have evaluations for decision-making some 3 months or more after the start of treatment, even with small-molecules and biological therapy, which are treatments that show a response in days or weeks.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Methotrexate is the cornerstone of initial treatment; it is accessible and provides adequate effectiveness and tolerability. The ACR guidelines, which are to be published in 2015, are based on the analysis of 102 clinical studies selected from 11,705 publications (Singh J, MacAlindon T, Saag K, Bridges SL, Akl E, Bannuru R, et al., 2015. <span class="elsevierStyleItalic">Recommendations for the treatment of rheumatoid arthritis</span>; oral presentation at ACR 2014, Boston). Leflunomide and sulfasalazine are mentioned as alternatives that are comparable to methotrexate in effectiveness and safety, although hydroxychloroquine is also considered for use as monotherapy, which may be unacceptable to many, even though it reduces disease progression in combination therapy and improves the metabolic profile.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> The future guidelines will also suggest that all RA patients should be evaluated by a rheumatologist and that, given the efficacy and fast action of glucocorticoids, these should be used; however, because of their adverse effects and accumulated damage, we should limit their use to the lowest dose and duration possible.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The EULAR recommendations suggest reducing, but not suspending, therapy with conventional synthetic disease-modifying antirheumatic drugs (DMARD) when remission is reached. In a systematic review and meta-analysis of 6 controlled clinical studies, after 24 months O’Mahony et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> reported that the relative risk of relapse or deterioration of RA was 0.31 (95% confidence interval: 0.16–0.57; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) when DMARD were suspended; those who remained in treatment had a lower probability of relapse. Wolde et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> evaluated 285 patients with established RA in treatment with DMARD for an average of 5 years (2–33), in remission during the previous year, who were randomised to continue with DMARD (142) or placebo (143), with an incidence of relapse of 22% and 38%, respectively (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002); factors associated with relapse were high maintenance dose (RR:3) and positive rheumatoid factor (RR:2.9). When Van der Woude et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> evaluated 2 cohorts, one by Leiden (68 out of 454 patients – 15%) and one from ERAS (84 out of 895 – 9.4%), criteria for remission were reached without the use of DMARD, with an average remission of 43 months; in the univariate analysis, in both cohorts there were 6 factors associated with remission: shorter evolution time, non-smoker, limited radiographic progression at baseline, seronegativity (rheumatoid factor and anti-citrullinated protein antibodies), and absence of shared epitope alleles. In the multivariate analysis from the Leiden cohort, 2 factors were associated with remission: C-reactive protein and anti-citrullinated protein antibody at the baseline evaluation; in the ERAS cohort, rheumatoid factor was an independent factor associated with DMARD-free remission.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Due to the infectious processes present in at least double the population exposed to biologics, when faced with a previous history of opportunistic or serious infections, Singh et al. state: keep in mind not to escalate to a TNF inhibitor (iTNF), and abatacept should be considered when a biologic is required, based on its safety; patients should also receive vaccines derived from attenuated living microorganisms before receiving biologics. However, it is interesting that patients with RA have increased risk for chickenpox infections and that the risk for herpes zoster is even greater during treatment with glucocorticoids (<span class="elsevierStyleUnderline">></span>10<span class="elsevierStyleHsp" style=""></span>mg de prednisone/d), with DMARD or biologics, and higher with the use of small molecules. Nonetheless, in zoster vaccination studies, not one patient out of the hundreds in treatment with biologics had disseminate varicella zoster; furthermore, with vaccination, and in spite of the biologic, the presentation of this infection was substantially reduced.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">We have learned that, in general, there is no increased cancer risk associated with current treatment in patients with RA, and patients with a history of non-melanoma skin CA can be treated with DMARD. In the case of melanoma, iTNF is used before tofacitinib; abatacept, tocilizumab or rituximab can be selected when there is a history of lymphoma. As for seropositivity for hepatitis B virus, DMARD are preferable in conjunction with adequate treatment to achieve viral load remission; when a biologic is required, use iTNF; for hepatitis C virus, other biologics and tofacitinib can also be selected. In patients with heart failure, it is preferable to use DMARD, other biologics and tofacitinib before iTNF, although the use of etanercept is acceptable.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The main comorbidities or extra-articular manifestations of RA should be considered, such as cardiovascular and osteoporosis. For both, vitamin D is an incontrovertible option, both for its metabolic effects as well as the potential pleiotropism for autoimmunity and cardiovascular health,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> a fact that could be extended to bisphosphonates, which reduce the rate of myocardial infarction by 28%, and potentially denosumab.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–17</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Increased cardiovascular risk in autoimmune inflammatory disease, especially RA, are well known.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18–21</span></a> Thus, in patients with RA, consideration should be given to the prevention and treatment of cardio- and cerebrovascular disease, particularly in those with one or more cardiovascular risk factors and in patients with established RA for more than 10 years, with seropositivity and extra-articular manifestations. Treatment, with the aim of also achieving remission of RA, should include smoking cessation, reduction or elimination of non-steroid and steroid anti-inflammatories, blood pressure normalisation, physical exercise and the use of statins.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22–24</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Indisputably, exercise provides benefits in addition to cardiovascular protection, including improved quality of life, pain, rigidity and fatigue in patients with RA, as well as the decrease in proinflammatory cytokines and, therefore, less local and systemic inflammation.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,25</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Thus, while rheumatologists attempt to achieve remission of RA as quickly as possible, we should also contemplate the comorbidities or extra-articular manifestations of the disease and escalate to optimal, complete treatment without restrictions for better quality of life and increased survival, which, in spite of our efforts, we still have not been able to achieve.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:2 [ 0 => array:3 [ "etiqueta" => "◊" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Members of the Mexican Workgroup for the Integral Management of Rheumatoid Arthritis are listed in the <a class="elsevierStyleCrossRef" href="#sec0005">Addendum</a>.</p>" "identificador" => "fn0005" ] 1 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Abud-Mendoza C, Coordinators of the Grupo Mexicano de Estudio de Manejo Integral de la Artritis Reumatoide. Consideraciones a las recomendaciones terapéuticas para la artritis reumatoide. Reumatol Clin. 2015. <span class="elsevierStyleInterRef" id="intr0005" href="doi:10.1016/j.reuma.2015.05.002">http://dx.doi.org/10.1016/j.reuma.2015.05.002</span></p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0065" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Marco Ulises Martínez-Martínez</span></span> (Unidad Regional de Reumatología y Osteoporosis, Hospital Central «Dr. Ignacio Morones Prieto»; and Facultad de Medicina de la Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico);</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Javier Merayo-Chalico</span></span> (Departamento de Reumatología e Inmunología, Instituto Nacional de Ciencias Médicas y Nutrición «Dr. Salvador Zubirán», México, DF, Mexico);</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Éufrates Hernández-Núñez</span></span> (Hospital Rovirosa SS y Hospital «Bartolomé Reynes Berezaluce» IMSS, Villahermosa Tabasco, Tab., Mexico);</p></li><li class="elsevierStyleListItem" id="lsti0015"><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Jorge Iván Gámez-Nava</span></span> (Hospital de Especialidades Centro Médico Nacional de Occidente, IMSS y Universidad de Guadalajara, Guadalajara, Jal., Mexico).</p></li></ul></p>" "etiqueta" => "Addendum" "titulo" => "Mexican Workgroup for the Integral Management of Rheumatoid Arthritis" "identificador" => "sec0005" ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 9 | 16 |
| 2024 October | 40 | 31 | 71 |
| 2024 September | 44 | 24 | 68 |
| 2024 August | 49 | 27 | 76 |
| 2024 July | 45 | 37 | 82 |
| 2024 June | 76 | 42 | 118 |
| 2024 May | 47 | 38 | 85 |
| 2024 April | 44 | 24 | 68 |
| 2024 March | 48 | 20 | 68 |
| 2024 February | 32 | 32 | 64 |
| 2024 January | 57 | 24 | 81 |
| 2023 December | 24 | 27 | 51 |
| 2023 November | 34 | 27 | 61 |
| 2023 October | 48 | 26 | 74 |
| 2023 September | 53 | 36 | 89 |
| 2023 August | 37 | 17 | 54 |
| 2023 July | 35 | 49 | 84 |
| 2023 June | 29 | 23 | 52 |
| 2023 May | 41 | 22 | 63 |
| 2023 April | 26 | 7 | 33 |
| 2023 March | 48 | 32 | 80 |
| 2023 February | 46 | 23 | 69 |
| 2023 January | 30 | 22 | 52 |
| 2022 December | 50 | 50 | 100 |
| 2022 November | 54 | 36 | 90 |
| 2022 October | 56 | 33 | 89 |
| 2022 September | 36 | 46 | 82 |
| 2022 August | 34 | 36 | 70 |
| 2022 July | 29 | 35 | 64 |
| 2022 June | 38 | 34 | 72 |
| 2022 May | 34 | 44 | 78 |
| 2022 April | 39 | 43 | 82 |
| 2022 March | 52 | 53 | 105 |
| 2022 February | 23 | 41 | 64 |
| 2022 January | 41 | 32 | 73 |
| 2021 December | 20 | 42 | 62 |
| 2021 November | 27 | 42 | 69 |
| 2021 October | 41 | 50 | 91 |
| 2021 September | 28 | 35 | 63 |
| 2021 August | 24 | 28 | 52 |
| 2021 July | 33 | 24 | 57 |
| 2021 June | 20 | 29 | 49 |
| 2021 May | 29 | 33 | 62 |
| 2021 April | 45 | 55 | 100 |
| 2021 March | 26 | 16 | 42 |
| 2021 February | 34 | 15 | 49 |
| 2021 January | 32 | 15 | 47 |
| 2020 December | 32 | 22 | 54 |
| 2020 November | 27 | 18 | 45 |
| 2020 October | 21 | 16 | 37 |
| 2020 September | 30 | 19 | 49 |
| 2020 August | 21 | 13 | 34 |
| 2020 July | 11 | 13 | 24 |
| 2020 June | 28 | 34 | 62 |
| 2020 May | 27 | 16 | 43 |
| 2020 April | 31 | 19 | 50 |
| 2020 March | 29 | 8 | 37 |
| 2018 May | 4 | 0 | 4 |
| 2018 April | 48 | 7 | 55 |
| 2018 March | 53 | 7 | 60 |
| 2018 February | 25 | 11 | 36 |
| 2018 January | 33 | 7 | 40 |
| 2017 December | 35 | 12 | 47 |
| 2017 November | 41 | 13 | 54 |
| 2017 October | 39 | 7 | 46 |
| 2017 September | 39 | 9 | 48 |
| 2017 August | 49 | 17 | 66 |
| 2017 July | 56 | 19 | 75 |
| 2017 June | 66 | 13 | 79 |
| 2017 May | 60 | 15 | 75 |
| 2017 April | 58 | 11 | 69 |
| 2017 March | 62 | 21 | 83 |
| 2017 February | 44 | 10 | 54 |
| 2017 January | 35 | 14 | 49 |
| 2016 December | 65 | 22 | 87 |
| 2016 November | 63 | 24 | 87 |
| 2016 October | 67 | 15 | 82 |
| 2016 September | 69 | 10 | 79 |
| 2016 August | 57 | 3 | 60 |
| 2016 July | 36 | 14 | 50 |
| 2015 December | 2 | 0 | 2 |
| 2015 November | 1 | 28 | 29 |
| 2015 October | 3 | 31 | 34 |
| 2015 September | 2 | 0 | 2 |
| 2015 August | 6 | 83 | 89 |
| 2015 July | 51 | 50 | 101 |
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