This study aims to estimate the effect of synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) on radiographic progression and quality of life in adult patients with psoriatic arthritis. A comprehensive search was performed using MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CCRCT). Clinical trials comparing DMARDs with placebo for ≥ 12 weeks were included. The meta-analysis was conducted with a random-effects model using mean differences (MD). A total of 16 trials with overall moderate quality of evidence were included. Exposure to a biologic agent reduced radiographic progression at 24 weeks of treatment (MD: - 0.66; [95% CI - 0.97 to - 0.34]; P < .00001; I2 = 100%). The reduction of the baseline score was more than two times higher for TNF blockers compared with IL-17 and IL-12/IL-23 inhibitors (MD: - 0.94 vs - 0.41). Improvement in health-related quality of life scores was observed in biologic-treated populations (MD: - 0.21; [95% CI - 0.25 to - 0.18]; P < .00001; I2 = 97%). No sufficient data were available regarding conventional synthetic agents. Our data analyses suggest a better control of radiological damage with bDMARDs, as compared to placebo, after 24 weeks of treatment. However, the accuracy of these results in real life are jeopardized by the exceedingly high level of heterogeneity exhibited within and across included studies, and the true intervention effect cannot be determined with confidence. Further research is required to assess long-term outcomes and to control heterogeneity in the evaluation of treatments for psoriatic arthritis. PROSPERO registration number: CRD42019122223. Key Points • Radiographic progression is not the primary outcome for most efficacy studies in psoriatic arthritis; hence, baseline data are substantially diverse in major clinical trials. • The best available evidence on this particular outcome is currently at a moderate risk of bias. • Existing reports of the effect of DMARDs on structural damage must be taken with caution. • Further research is required to assess long-term outcomes and to control heterogeneity between studies.
Background: Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review. Methods: The systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist. We selected randomized controlled trials (RCTs) that looked at the impact of interventions with disease-modifying agents, either synthetic drugs or biologics on musculoskeletal outcomes, notably American College of Rheumatology 20 percent responders. Results were analyzed using Review Manager 5.1.6 (Cochrane Collaboration, Oxford, UK). Whilst our primary focus was on published trials, we also looked at new trials presented in abstract form in 2013-2014 that were not yet published to avoid omitting important and up-to-date information on developing treatments. Results: Our in-depth analysis included 28 trials overall enrolling 5,177 patients published between the 1980s and now as well as limited analysis of some studies in abstract form as described earlier. The most frequently available locomotor outcome measure was the American College of Rheumatology 20 percent responders. The risk ratio for achieving an American College of Rheumatology 20 percent responders response was positive in favor of treatment (risk ratio 2.30; 95% confidence interval 1.78-2.96); however, there was evidence of considerable heterogeneity between trials. Overall randomized controlled trials of established synthetic disease-modifying agents were largely negative (methotrexate, ciclosporin and sulfasalazine) though leflunomide showed a small positive effect. A new synthetic agent, apremilast, did show a positive benefit. For biologics, TNF inhibitors already licensed for use were effective and similar benefits were seen with newer agents including ustekinumab, secukinumab, brodalumab, and abatacept, although the latter did not impact on skin problems. Important limitations of the systematic review included, first, the fact that for many agents there were little data and, second, much of the recent data for newer biologics were only available in abstract form. Conclusion: Conventional disease-modifying agents, with the possible exception of lefluno-mide, do not show clear evidence of disease-modifying effects in psoriatic arthritis, though a newer synthetic disease-modifying agents, apremilast, appears more effective. Biologic agents appear more beneficial, although more evidence is required for newer agents. This review suggests that it may be necessary to review existing national and international management guidelines for psoriatic arthritis.
INTRODUCCIÓN: El tratamiento farmacológico actual de espondiloartritis (SpA) incluye varios medicamentos: medicamentos antiinflamatorios no esteroideos, corticoides, fármacos antirreumáticos modificadores de la enfermedad tradicionales y fármacos biológicos.
Zonas cubiertas: se completó una búsqueda sistemática de la literatura utilizando las bases de datos electrónicas más grandes (Medline, Embase y Cochrane), a partir de 1995, con el objetivo de revisar los datos de los agentes tradicionales y biológicos comercializados para el tratamiento SpA. Se consideraron los ensayos controlados aleatorios y los grandes estudios observacionales. Además, los estudios realizados en pacientes tratados con otros SpA, aún no aprobado, drogas (rituximab, agentes anti-IL6, Apremilast, inhibidores de IL17 y anakinra) también fueron tomadas en cuenta.
DICTAMEN DE EXPERTOS: Los agentes biológicos, especialmente los fármacos anti-TNF, se han traducido en avances significativos en la mejora de los síntomas y signos clínicos, reduciendo características inflamatorias en las pruebas de laboratorio y los hallazgos de imagen, y la recuperación de todos los índices funcionales. Los fármacos anti-TNF han cambiado radicalmente la evolución de la progresión radiográfica en articulaciones periféricas; los primeros datos decepcionantes en cuanto a su eficacia en la formación de hueso nuevo de SpA axial ha sido cuestionado recientemente por estudios que incluían a pacientes que han sido diagnosticados y tratados antes. La oportunidad de ampliar el intervalo de administración o reducir las dosis de los agentes anti-TNF puede influir favorablemente en los costos. Ustekinumab, el primer medicamento biológico no anti-TNF comercializada para la artritis psoriásica, ofrece nuevas posibilidades a los pacientes que no responden a anti-TNF.
In 2009, GRAPPA published their first evidence-based recommendations for the treatment of psoriasis and psoriatic arthritis (PsA). Since then, new information has been published and drugs developed. We summarize evidence for the efficacy of available treatments for peripheral joint involvement in PsA. We performed a systematic review of current literature on the efficacy of different therapies, management, and therapeutic strategies for peripheral arthritis involvement in PsA, in order to provide information for the development of the new GRAPPA treatment recommendations.
Existen numerosas directrices y recomendaciones para el tratamiento de la psoriasis en diversas poblaciones. Una población importante son los pacientes con artritis psoriásica (PsA) que tienen síntomas de la enfermedad de la articulación y la piel. En pacientes con ambas facetas de la enfermedad psoriásica, la piel y las articulaciones deben tratarse por separado, pero también simultáneamente. Como varias terapias sistémicas son aprobadas para uno o ambos, el concepto de tratar ambas facetas con el mismo fármaco es factible. Esta revisión resume la evidencia de los estudios en pacientes con PsA sobre la eficacia de estos fármacos sobre la enfermedad psoriásica de la piel en estos pacientes.
La evidencia apoya el uso temprano de FARME no biológicos para evitar daños irreversibles en artritis inflamatorias, incluyendo la artritis reumatoide (AR), artritis psoriásica (APs), y, posiblemente, la espondilitis anquilosante (EA). Sin embargo, hay una escasez de datos que exploran sus efectos sobre el dolor como un resultado primario en estas condiciones. Esta revisión de la literatura sistemática investigó el efecto de FARME no biológicos en los niveles de dolor en IA y examinó si la duración de la enfermedad afectada la eficacia. Se hicieron búsquedas en Medline, Embase, Cochrane Central y Base de Datos Cochrane de,, las listas de referencias de publicaciones recuperados Revisiones Sistemáticas resúmenes de la American College of Rheumatology congresos anuales 2008-2010 y. Se analizaron los ensayos controlados Sólo aleatorizados, doble ciegos. La calidad se evaluó con la herramienta de riesgo de sesgo. Se utilizó estadística descriptiva en el metanálisis. Se identificaron 9.860 artículos, con 33 requisitos para la inclusión: 8 en el autómata, 6 en la artritis psoriásica, 9 en la AR temprana (ERA), y 10 en la AR establecida. En la era de la AR establecida, todos los estudios de FAME (monoterapia y tratamientos combinados) revelaron sistemáticamente reducciones estadísticamente significativas en el dolor, excepto tres estudios oro orales. En AS, sulfasalazina estudios mostraron una reducción significativa del dolor, mientras que el uso de otros FARME no. En la artritis psoriásica, 5 de 6 estudios informaron mejoría VAS-dolor. De los estudios incluidos, no fue posible evaluar la influencia de la duración de la enfermedad en los resultados de dolor en las enfermedades reumáticas. FAME mejorar el dolor en la primera y la AR establecida. La sulfasalazina puede mejorar el dolor en la EA y APs. Se necesitan más estudios para evaluar la relación entre la duración de la enfermedad y la eficacia DMARD para reducir el dolor en estas condiciones.
Psoriatic arthritis (PsA) is a chronic, progressive, and debilitating disorder. When monotherapy fails, combination therapy is necessary for the long-term management of these patients. There is currently no review on this subject, and the purpose of this study was to investigate and describe the current literature on combination therapy in PsA. A PubMed MeSH search was performed for psoriatic arthritis and combination therapy, which yielded at total of 83 articles. After excluding reviews and commentaries, and pursuing relevant citations, a total of 21 articles on the subject were found: one study of NSAIDs and methotrexate, three studies of cyclosporine and methotrexate, three studies of non-TNF biologic inhibitors (alefacept, ustekinumab) and methotrexate, and 14 studies of anti-TNF-inhibitors (etanercept, adalimumab, infliximab, golimumab) and methotrexate. The combination of cyclosporine and methotrexate reduces the dosages and also the side effects of each agent, allowing better disease control with less toxicity. Methotrexate in combination with biologic agents, either non-TNF inhibitors or anti-TNF inhibitors, may have a role in decreasing side effects, but it does not appear to improve clinical symptoms beyond those attained by biologic monotherapy.
This study aims to estimate the effect of synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) on radiographic progression and quality of life in adult patients with psoriatic arthritis. A comprehensive search was performed using MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CCRCT). Clinical trials comparing DMARDs with placebo for ≥ 12 weeks were included. The meta-analysis was conducted with a random-effects model using mean differences (MD). A total of 16 trials with overall moderate quality of evidence were included. Exposure to a biologic agent reduced radiographic progression at 24 weeks of treatment (MD: - 0.66; [95% CI - 0.97 to - 0.34]; P < .00001; I2 = 100%). The reduction of the baseline score was more than two times higher for TNF blockers compared with IL-17 and IL-12/IL-23 inhibitors (MD: - 0.94 vs - 0.41). Improvement in health-related quality of life scores was observed in biologic-treated populations (MD: - 0.21; [95% CI - 0.25 to - 0.18]; P < .00001; I2 = 97%). No sufficient data were available regarding conventional synthetic agents. Our data analyses suggest a better control of radiological damage with bDMARDs, as compared to placebo, after 24 weeks of treatment. However, the accuracy of these results in real life are jeopardized by the exceedingly high level of heterogeneity exhibited within and across included studies, and the true intervention effect cannot be determined with confidence. Further research is required to assess long-term outcomes and to control heterogeneity in the evaluation of treatments for psoriatic arthritis. PROSPERO registration number: CRD42019122223. Key Points • Radiographic progression is not the primary outcome for most efficacy studies in psoriatic arthritis; hence, baseline data are substantially diverse in major clinical trials. • The best available evidence on this particular outcome is currently at a moderate risk of bias. • Existing reports of the effect of DMARDs on structural damage must be taken with caution. • Further research is required to assess long-term outcomes and to control heterogeneity between studies.
