Case report
Tocilizumab in a Patient With Tophaceous Gout Resistant to Treatment
Tocilizumab en paciente con gota tofácea severa refractaria al tratamiento
Jessica L. Pinto, Gloria E. Mora, Daniel G. Fernández-Avila
, Juan M. Gutiérrez, María C. Díaz, Grupo Javeriano de Investigación en Enfermedades Reumáticas
Corresponding author
Unidad de Reumatología, Departamento de Medicina Interna, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia
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Pinto, Gloria E. Mora, Daniel G. Fernández-Avila, Juan M. Gutiérrez, María C. Díaz" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Jessica L." "apellidos" => "Pinto" ] 1 => array:2 [ "nombre" => "Gloria E." "apellidos" => "Mora" ] 2 => array:4 [ "nombre" => "Daniel G." "apellidos" => "Fernández-Avila" "email" => array:1 [ 0 => "danielfernandezmd@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 3 => array:2 [ "nombre" => "Juan M." "apellidos" => "Gutiérrez" ] 4 => array:2 [ "nombre" => "María C." "apellidos" => "Díaz" ] 5 => array:1 [ "colaborador" => "Grupo Javeriano de Investigación en Enfermedades Reumáticas" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Unidad de Reumatología, Departamento de Medicina Interna, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tocilizumab en paciente con gota tofácea severa refractaria al tratamiento" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Gout is a disease characterized by acute inflammatory episodes caused by precipitation and deposition of monosodium urate crystals (MUC) in the joints. It is the most common cause of inflammatory arthritis in men under 40 and affects approximately 1% of the adult population.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Major advances in understanding its pathogenesis and treatment have been made in the last decade and include the identification of genetic and environmental factors, as well as recognition of gout as a major risk factor for cardiovascular disease.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Recent studies in animals and humans suggest that MUC elicit an inflammatory response that will trigger nitric oxide, prostaglandins, and tumor necrosis factor alpha (TNF-α), IL-6, proinflammatory cytokines such as IL-1, IL-1β, produced by macrophages, dendritic cells and monocytes as well as the presence of the NLRP<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> inflammasome complex (intracellular proteolytic complex).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">That is why we evaluated the pharmacological response to IL-1 inhibitors, including rilonacept; the results indicate a reduction in the frequency of gouty attacks during the initial period of treatment with the uricosuric drugs,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and thus opened the door to evaluate other therapies.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Clinical Observation</span><p id="par0025" class="elsevierStylePara elsevierViewall">We present the case of a 44 years old man with severe uncontrolled tophaceous gouty arthritis of 12 years of evolution, with the presence of tophi in knees, elbows, feet, and with polyarticular inflammatory pain that hindered functionality, with a pain visual analogue scale score of 7/10. He had a history of medical treatment and surgical resection of gouty tophi in the feet and elbows. His previous management included the use of colchicine 0.5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h, allopurinol 300<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h, diclofenac 75<span class="elsevierStyleHsp" style=""></span>mg/dl, receiving treatment for about eight years, without improvement despite 100% compliance.</p><p id="par0030" class="elsevierStylePara elsevierViewall">On physical examination, the patient had limitation for walking and tophi of 3–5<span class="elsevierStyleHsp" style=""></span>cm in diameter on the hands, elbows, knees and feet. Radiographs showed multiple punched out erosions that compromised the phalanges of the hands and feet, decreased intercarpal joint spaces, loss of relationship of the metacarpophalangeal joints, metatarsophalangeal joint subluxation of the left first toe, and remodeling of the left fifth metatarsal.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the presence of a pattern of severe treatment-resistant tophaceous gout, management was begun with tocilizumab at a dose of 8<span class="elsevierStyleHsp" style=""></span>mg/kg/month. The evaluation after the start of treatment showed that the patient has had no further gouty attacks and regained his ability to perform basic activities of self-care. There was no evident decrease in the size or number of tophi. Laboratory findings are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Acute treatment of gouty arthritis focuses on the use of NSAIDs, colchicine and glucocorticoids, however adequate chronic treatment is required to decrease the frequency of exacerbations and disease progression. Drugs that have been evaluated for the maintenance of patients can be divided into inhibitors of xanthine oxidase, the uricosuric uricase and those which modulate the inflammatory process. Allopurinol, belongs to the first group and is the cornerstone of chronic treatment, but its adverse effects and the high frequency with which recurrent episodes of gout occur during treatment have led to a search for other drugs.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Among the new drugs highlighted, rasburicase and pegloticase, which catalyze the conversion of urate to allantoin, reduce uric acid levels. The use of pegloticase has shown useful for maintaining uric acid levels below 6<span class="elsevierStyleHsp" style=""></span>mg/dl in up to 47% of patients,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> as well as in reducing tophi<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> after 12 weeks. However, it is not available in our country.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The drugs related to the regulation of the inflammatory process in gout are based on the regulation of the high levels of TNF-α, as well as IL-1 and IL-6. These drugs include anti-TNF (infliximab<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and etanercept<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>), anakinra and rilonacept, which are competitive inhibitors of IL-1,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and canakinumab, which neutralizes the bioactivity of IL-1β.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Current evidence is limited to cases where anti-TNF (infliximab and etanercept) and competitive inhibitors of IL-1 have been used, with which there is a modulation of pain related to the inflammatory response. Anakinra was used for treatment in a series of 10 cases, in which there was a favorable response in six patients. In the case of canakinumab, Schlesinger et al. conducted two clinical studies, the first in 2011, which demonstrated the superiority of this drug over colchicine for reducing gout symptoms after alopurinol<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> was started. The second shows the effectiveness of canakinumab in improving pain and inflammation, and a decrease in the risk of new acute crises.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The case presented shows an adequate response to treatment with tocilizumab, highlighting disease control from the clinical point of view and the results of laboratory tests, which can be considered as related to IL-6 as a potential therapeutic target,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> but this is only one report of a successful case and it should be noted that the cost of biologic therapy is more than 100 times the cost of therapy with allopurinol and up to five times the cost of pegloticase.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusion</span><p id="par0065" class="elsevierStylePara elsevierViewall">We describe an appropriate response to biological treatment with tocilizumab in the context of a patient with severe gouty arthritis. Further studies are required to evaluate the effectiveness of this treatment in the context of this disease.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Protection of human and animal subjects.</span> The authors declare that no experiments were performed on humans or animals for this investigation.</p><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Confidentiality of Data.</span> The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Right to privacy and informed consent.</span> The authors have obtained the informed consent of the patients and /or subjects mentioned in the article. The author for correspondence is in possession of this document.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have no disclosures to make.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres243412" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec229961" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres243411" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec229962" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical Observation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Ethical disclosures" ] 9 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-12-31" "fechaAceptado" => "2012-06-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec229961" "palabras" => array:3 [ 0 => "Severe tophaceous gout" 1 => "Rheumatoid arthritis" 2 => "Tocilizumab" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec229962" "palabras" => array:3 [ 0 => "Gota" 1 => "Inflamación" 2 => "Tocilizumab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Gout is a disease characterized by acute episodes of pain, which occurs as the result of monosodic urate crystal deposit in the joint and periarticular tissue. In some cases, gout behaves as a severe inflammatory arthopathy that is difficult to manage, generating structural joint damage and functional impairment. We report the case of a 44 years old man with gouty arthritis for 12 years, not responding to NSAIDs, alopurinol, colchicine or corticosteroids. Tocilizumab was started with favorable clinical and laboratory results after treatment.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La gota es una enfermedad que se caracteriza por episodios agudos de dolor como consecuencia del depósito de cristales de urato monosódico en las articulaciones y en el tejido periarticular. En algunos casos, la gota se comporta como una artropatía inflamatoria severa de difícil manejo, generándose daño estructural articular y alteración funcional secundaria. Presentamos el caso de un hombre de 44 años con artritis gotosa tofácea severa de 12 años de evolución, sin respuesta al manejo con AINE, alopurinol, colchicina y corticoides, a quien se inició tratamiento con tocilizumab, con favorable respuesta clínica y paraclínica.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please, cite this article as: Pinto JL, et al. Tocilizumab en paciente con gota tofácea severa refractaria al tratamiento. Reumatol Clin. 2012. <span class="elsevierStyleInterRef" href="doi:10.1016/j.reuma.2012.06.009">http://dx.doi.org/10.1016/j.reuma.2012.06.009</span>.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Before Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">6 Weeks After Onset of Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">12 Weeks After Onset of Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">18 Weeks After Onset of Treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Uric acid \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">9.7<span class="elsevierStyleHsp" style=""></span>mg/dl \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">8.1<span class="elsevierStyleHsp" style=""></span>mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">CRP<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">6<span class="elsevierStyleHsp" style=""></span>mg/l \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">0.4<span class="elsevierStyleHsp" style=""></span>mg/l \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">0.1<span class="elsevierStyleHsp" style=""></span>mg/l \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">0.2<span class="elsevierStyleHsp" style=""></span>mg/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">ESR \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">45<span class="elsevierStyleHsp" style=""></span>mm/seg \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">12<span class="elsevierStyleHsp" style=""></span>mm/seg \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">12<span class="elsevierStyleHsp" style=""></span>mm/seg \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<span class="elsevierStyleHsp" style=""></span>mm/seg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Visual analog scale pain \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">7/10 \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">2/10 \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">1/10 \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">0/10 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab351509.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">Normal value: less than 0.5.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Monitoring Activity of Disease During Treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The modern management of gout" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.G. Rider" 1 => "K.M. Jordan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/kep306" "Revista" => array:7 [ "tituloSerie" => "Rheumatology" "fecha" => "2010" "volumen" => "49" "paginaInicial" => "5" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19808695" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0014256510003413" "estado" => "S300" "issn" => "00142565" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of the NLRP3 inflammasome in gout" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.R. Kingsbury" 1 => "P.G. Conaghan" 2 => "M.F. McDermott" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/JIR.S11330" "Revista" => array:6 [ "tituloSerie" => "Journal of Inflammation Research" "fecha" => "2011" "volumen" => "4" "paginaInicial" => "39" "paginaFinal" => "49" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22096368" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "0619 Study Group" "etal" => true "autores" => array:6 [ 0 => "H.R. Schumacher Jr." 1 => "J.S. Sundy" 2 => "R. Terkeltaub" 3 => "H.R. Knapp" 4 => "S.J. Mellis" 5 => "N. Stahl" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.33412" "Revista" => array:7 [ "tituloSerie" => "Arthritis and Rheumatism" "fecha" => "2012" "volumen" => "64" "paginaInicial" => "876" "paginaFinal" => "884" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22223180" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0091674901209117" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperuricaemia and gout: state of the art and future perspectives" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Dalbeth" 1 => "A. So" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.136218" "Revista" => array:6 [ "tituloSerie" => "Annals of the Rheumatic Diseases" "fecha" => "2010" "volumen" => "69" "paginaInicial" => "1738" "paginaFinal" => "1743" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20858623" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gout. Novel therapies for treatment of gout and hyperuricemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Terkeltaub" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/ar2738" "Revista" => array:5 [ "tituloSerie" => "Arthritis Research and Therapy" "fecha" => "2009" "volumen" => "11" "paginaInicial" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19664185" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.S. Sundy" 1 => "H.S. Baraf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2011.1169" "Revista" => array:6 [ "tituloSerie" => "Journal of the American Medical Association" "fecha" => "2011" "volumen" => "306" "paginaInicial" => "711" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21846852" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resolution of gouty tophi after twelve weeks of pegloticase treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H.S. Baraf" 1 => "A.K. Matsumoto" 2 => "A.N. Maroli" 3 => "R.W. Waltrip" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.23993" "Revista" => array:6 [ "tituloSerie" => "Arthritis and Rheumatism" "fecha" => "2008" "volumen" => "58" "paginaInicial" => "3632" "paginaFinal" => "3634" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18975338" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of chronic tophaceous gout with infliximab (Remicade)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Fiehn" 1 => "M. Zeier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00296-005-0617-7" "Revista" => array:6 [ "tituloSerie" => "Rheumatology International" "fecha" => "2006" "volumen" => "26" "paginaInicial" => "274" "paginaFinal" => "276" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15933855" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe gouty arthritis refractory to anti-inflammatory drugs: treatment with anti-tumour necrosis factor alpha as a new therapeutic option" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.K. Tausche" 1 => "K. Richter" 2 => "A. Grässler" 3 => "S. Hänsel" 4 => "B. Roch" 5 => "H.E. Schröder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2003.015743" "Revista" => array:7 [ "tituloSerie" => "Annals of the Rheumatic Diseases" "fecha" => "2004" "volumen" => "63" "paginaInicial" => "1351" "paginaFinal" => "1352" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15361402" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0014256512000616" "estado" => "S300" "issn" => "00142565" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anakinra's efficacy is variable in refractory gout: report of ten cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K. Chen" 1 => "T. Fields" 2 => "C.A. Mancuso" 3 => "A.R. Bass" 4 => "L. Vasanth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semarthrit.2010.03.001" "Revista" => array:6 [ "tituloSerie" => "Seminars in Arthritis and Rheumatism" "fecha" => "2010" "volumen" => "40" "paginaInicial" => "210" "paginaFinal" => "214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20494407" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double blind, randomized study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Schlesinger" 1 => "E. Mysler" 2 => "H.Y. Lin" 3 => "M. De Meulemeester" 4 => "J. Rovensky" 5 => "U. Arulmani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.144063" "Revista" => array:7 [ "tituloSerie" => "Annals of the Rheumatic Diseases" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "1264" "paginaFinal" => "1271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21540198" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S001425651000305X" "estado" => "S300" "issn" => "00142565" ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomized, multicentre, active-controlled, double blind trials and their initial extensions" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Schlesinger" 1 => "R.E. Alten" 2 => "T. Bardin" 3 => "H.R. Schumacher" 4 => "M. Bloch" 5 => "A. Gimona" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2011-200908" "Revista" => array:6 [ "tituloSerie" => "Annals of the Rheumatic Diseases" "fecha" => "2012" "volumen" => "71" "paginaInicial" => "1839" "paginaFinal" => "1848" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22586173" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of polymorphisms in the promoter region and protein levels of interleukin-6 gene among gout patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P.C. Tsai" 1 => "C.J. Chen" 2 => "H.M. Lai" 3 => "S.J. Chang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clinical and Experimental Rheumatology" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "841" "paginaFinal" => "847" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19032817" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000000900000003/v1_201307311407/S2173574312001645/v1_201307311407/en/main.assets" "Apartado" => array:4 [ "identificador" => "17376" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Case Report" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000900000003/v1_201307311407/S2173574312001645/v1_201307311407/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574312001645?idApp=UINPBA00004M" ]
| Year/Month | Html | Total | |
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| 2024 November | 15 | 19 | 34 |
| 2024 October | 67 | 52 | 119 |
| 2024 September | 61 | 25 | 86 |
| 2024 August | 76 | 37 | 113 |
| 2024 July | 49 | 33 | 82 |
| 2024 June | 65 | 26 | 91 |
| 2024 May | 89 | 37 | 126 |
| 2024 April | 45 | 18 | 63 |
| 2024 March | 51 | 37 | 88 |
| 2024 February | 33 | 16 | 49 |
| 2024 January | 43 | 22 | 65 |
| 2023 December | 32 | 37 | 69 |
| 2023 November | 27 | 18 | 45 |
| 2023 October | 45 | 31 | 76 |
| 2023 September | 73 | 30 | 103 |
| 2023 August | 27 | 23 | 50 |
| 2023 July | 32 | 22 | 54 |
| 2023 June | 32 | 42 | 74 |
| 2023 May | 41 | 21 | 62 |
| 2023 April | 46 | 14 | 60 |
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| 2022 December | 47 | 30 | 77 |
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| 2022 April | 66 | 47 | 113 |
| 2022 March | 53 | 45 | 98 |
| 2022 February | 59 | 46 | 105 |
| 2022 January | 37 | 40 | 77 |
| 2021 December | 30 | 41 | 71 |
| 2021 November | 39 | 48 | 87 |
| 2021 October | 54 | 44 | 98 |
| 2021 September | 51 | 44 | 95 |
| 2021 August | 44 | 51 | 95 |
| 2021 July | 29 | 42 | 71 |
| 2021 June | 43 | 48 | 91 |
| 2021 May | 54 | 51 | 105 |
| 2021 April | 137 | 92 | 229 |
| 2021 March | 85 | 33 | 118 |
| 2021 February | 71 | 28 | 99 |
| 2021 January | 44 | 27 | 71 |
| 2020 December | 33 | 26 | 59 |
| 2020 November | 48 | 16 | 64 |
| 2020 October | 34 | 18 | 52 |
| 2020 September | 52 | 38 | 90 |
| 2020 August | 37 | 19 | 56 |
| 2020 July | 36 | 15 | 51 |
| 2020 June | 31 | 21 | 52 |
| 2020 May | 23 | 19 | 42 |
| 2020 April | 37 | 29 | 66 |
| 2020 March | 37 | 4 | 41 |
| 2020 February | 1 | 0 | 1 |
| 2020 January | 4 | 0 | 4 |
| 2019 September | 4 | 0 | 4 |
| 2019 June | 1 | 0 | 1 |
| 2019 March | 1 | 0 | 1 |
| 2019 January | 1 | 0 | 1 |
| 2018 December | 2 | 0 | 2 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 45 | 11 | 56 |
| 2018 March | 53 | 7 | 60 |
| 2018 February | 36 | 10 | 46 |
| 2018 January | 21 | 3 | 24 |
| 2017 December | 34 | 7 | 41 |
| 2017 November | 32 | 11 | 43 |
| 2017 October | 31 | 3 | 34 |
| 2017 September | 32 | 18 | 50 |
| 2017 August | 40 | 10 | 50 |
| 2017 July | 28 | 8 | 36 |
| 2017 June | 49 | 7 | 56 |
| 2017 May | 54 | 18 | 72 |
| 2017 April | 35 | 13 | 48 |
| 2017 March | 38 | 4 | 42 |
| 2017 February | 24 | 5 | 29 |
| 2017 January | 33 | 3 | 36 |
| 2016 December | 67 | 15 | 82 |
| 2016 November | 39 | 4 | 43 |
| 2016 October | 74 | 8 | 82 |
| 2016 September | 80 | 5 | 85 |
| 2016 August | 84 | 6 | 90 |
| 2016 July | 36 | 8 | 44 |
| 2016 June | 1 | 0 | 1 |
| 2016 May | 1 | 0 | 1 |
| 2016 April | 1 | 0 | 1 |
| 2016 March | 4 | 13 | 17 |
| 2016 February | 1 | 0 | 1 |
| 2016 January | 2 | 0 | 2 |
| 2015 December | 3 | 0 | 3 |
| 2015 October | 2 | 11 | 13 |
| 2015 September | 2 | 13 | 15 |
| 2015 August | 3 | 0 | 3 |
| 2015 July | 20 | 6 | 26 |
| 2015 June | 39 | 6 | 45 |
| 2015 May | 54 | 6 | 60 |
| 2015 April | 49 | 12 | 61 |
| 2015 March | 59 | 7 | 66 |
| 2015 February | 50 | 6 | 56 |
| 2015 January | 46 | 9 | 55 |
| 2014 December | 63 | 10 | 73 |
| 2014 November | 47 | 10 | 57 |
| 2014 October | 44 | 14 | 58 |
| 2014 September | 48 | 11 | 59 |
| 2014 August | 54 | 16 | 70 |
| 2014 July | 56 | 20 | 76 |
| 2014 June | 62 | 12 | 74 |
| 2014 May | 85 | 15 | 100 |
| 2014 April | 61 | 8 | 69 |
| 2014 March | 64 | 19 | 83 |
| 2014 February | 40 | 11 | 51 |
| 2014 January | 46 | 18 | 64 |
| 2013 December | 56 | 10 | 66 |
| 2013 November | 44 | 11 | 55 |
| 2013 October | 48 | 11 | 59 |
| 2013 September | 38 | 9 | 47 |
| 2013 August | 55 | 31 | 86 |
| 2013 July | 107 | 28 | 135 |
| 2013 June | 51 | 24 | 75 |
| 2013 May | 10 | 8 | 18 |
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