Despite recommendations suggesting that biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) should be used in combination with methotrexate in the treatment of rheumatoid arthritis (RA), up to one-third of patients with RA are treated with monotherapy. The objective of the systematic literature review reported here was to evaluate the clinical evidence regarding the efficacy of b/tsDMARDs as monotherapy in the treatment of RA. MEDLINE®, Embase®, and the Cochrane Central Trials Register (to April 11, 2017) and the American College of Rheumatology and European League Against Rheumatism conference proceedings (2010-2016) were searched for randomized controlled trials evaluating the efficacy of b/tsDMARDs as monotherapy for RA in adults. Forty-four monotherapy studies of abatacept, adalimumab, baricitinib, certolizumab pegol, etanercept, sarilumab, sirukumab, tocilizumab, and tofacitinib reported in 71 publications were identified. Tocilizumab had the most studies (14), followed by etanercept (10) and adalimumab (9). These b/tsDMARDs were consistently shown to be efficacious treatments, regardless of whether patients were intolerant of or had never used conventional synthetic (cs) DMARDs. However, better treatment outcomes were usually achieved with combination therapy, and this was observed for all b/tsDMARDs assessed by this review. Only a few studies provided a head-to-head comparison between b/tsDMARD treatments or between b/tsDMARD monotherapy and combination therapy, and as many were initial RA treatments they were not generalizable to usual care. In conclusion, evidence from randomized trials suggests that the b/tsDMARDs studied are effective as monotherapy. In general, some patient responses seem better with combination therapy and the durability of monotherapy is less than combination therapy. There is, however, a need for longer-term head-to-head trials to establish positioning of these interventions in the treatment algorithm for RA.
FUNDING: Pfizer.Plain Language Summary: Plain language summary available on the journal website.
OBJETIVOS: Actualizar una revisión sistemática anterior evaluación de la eficacia de los fármacos convencionales sintéticos antirreumáticos modificadores de la enfermedad (csDMARDs) en la artritis reumatoide (AR).
MÉTODOS: Dos revisiones sistemáticas de la literatura utilizando PubMed, Embase y la biblioteca Cochrane se realizaron a partir de 2009 hasta enero de 2013 para evaluar la eficacia de csDMARDs (como monoterapia o terapia combinada) en adultos con AR, y la eficacia de los glucocorticoides en la AR temprana. Una tercera revisión sistemática se llevó a cabo hasta marzo de 2013 para evaluar la eficacia de tofacitinib por el meta-análisis.
RESULTADOS: Para los glucocorticoides, de 222 golpes, se analizaron cinco publicaciones relacionadas con cuatro nuevos ensayos de eficacia, lo que confirma que el tratamiento inicial de la AR con prednisona en dosis bajas más metotrexato (MTX) se traduce en mejores resultados clínicos y estructurales a 1 y 2 años que tratamiento con MTX solo. Para csDMARDs, de 498 estudios, sólo dos nuevos estudios eran ensayos controlados aleatorios que comparaban el MTX en monoterapia con MTX en combinación con otro csDMARD sin diferencias en el uso de glucocorticoides. Utilizando los principios de control ajustados, los resultados clínicos no fueron mejores con la triple terapia inmediata que con el tratamiento 'step-up'. Para tofacitinib, el análisis combinado de 10 estudios mostró que tofacitinib fue más eficaz en los signos y síntomas, la discapacidad y parecía ser más eficaz en el daño estructural que el tratamiento de control con placebo (OR (IC del 95%) -American College of Rheumatology 20% ( ACR20) Respuesta: 2,44 (1,97-3,02)) o tratamiento con MTX respuesta (ACR20: 2,38 (1,66-3,43)).
CONCLUSIONES: La adición de glucocorticoides de dosis baja para terapia csDMARD produce beneficios en la AR temprana. Bajo condiciones de control ajustados, la terapia de combinación con csDMARDs no es mejor que MTX en monoterapia. Tofacitinib es un nuevo DMARD con eficacia probada.
Despite recommendations suggesting that biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) should be used in combination with methotrexate in the treatment of rheumatoid arthritis (RA), up to one-third of patients with RA are treated with monotherapy. The objective of the systematic literature review reported here was to evaluate the clinical evidence regarding the efficacy of b/tsDMARDs as monotherapy in the treatment of RA. MEDLINE®, Embase®, and the Cochrane Central Trials Register (to April 11, 2017) and the American College of Rheumatology and European League Against Rheumatism conference proceedings (2010-2016) were searched for randomized controlled trials evaluating the efficacy of b/tsDMARDs as monotherapy for RA in adults. Forty-four monotherapy studies of abatacept, adalimumab, baricitinib, certolizumab pegol, etanercept, sarilumab, sirukumab, tocilizumab, and tofacitinib reported in 71 publications were identified. Tocilizumab had the most studies (14), followed by etanercept (10) and adalimumab (9). These b/tsDMARDs were consistently shown to be efficacious treatments, regardless of whether patients were intolerant of or had never used conventional synthetic (cs) DMARDs. However, better treatment outcomes were usually achieved with combination therapy, and this was observed for all b/tsDMARDs assessed by this review. Only a few studies provided a head-to-head comparison between b/tsDMARD treatments or between b/tsDMARD monotherapy and combination therapy, and as many were initial RA treatments they were not generalizable to usual care. In conclusion, evidence from randomized trials suggests that the b/tsDMARDs studied are effective as monotherapy. In general, some patient responses seem better with combination therapy and the durability of monotherapy is less than combination therapy. There is, however, a need for longer-term head-to-head trials to establish positioning of these interventions in the treatment algorithm for RA.
FUNDING:
Pfizer.Plain Language Summary: Plain language summary available on the journal website.
