Background: Methotrexate (MTX) is widely used as a disease modifying drug (DMARD) in psoriatic arthritis (PsA) without definitive supporting clinical trial evidence. We tested its effectiveness in the first large multicentre randomised controlled trial (RCT) of MTX in active PsA (MIPA). Methods: A 6-month double-blind RCT compared oral MTX (15mg/week) with placebo in patients with active PsA. The primary outcome measure was the PsA Response Criteria (PsARC); other composite measures included ACR20 and DAS28. We analysed changes in individual measures including “disease modifying” (joint counts, HAQ, ESR and CRP) and “symptom modifying” (global assessments and pain) measures, skin and nail scores. Results: 462 patients were screened and 221 recruited. 71/109 (65%) of those who received MTX and 77/112 (69%) of those who received placebo completed 6 months therapy. 19 patients (11 MTX, 8 placebo) withdrew for toxicity and 22 (8 MTX, 14 placebo) for inefficacy. No significant treatment effects were seen on PsARC, ACR20 and DAS28 at 3 or 6 months using intention to treat logistic regression analysis (including multiple imputations for missing data and adjustment for age and sex). (Figure presented) There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ, pain and nail scores using ordinal linear regression analyses (adjusted for age, sex, baseline scores and disease duration). Patient and physician global scores and skin scores did improve with MTX compared to placebo but at 6 months only (p=0.03, p=0.02 and p=0.02). Separate analysis of polyarticular and oligoarticular PsA subsets also showed no treatment effect for PsARC, ACR20 and DAS28 at 3 or 6 months. Conclusions: Contrary to general opinion, MTX does not act as a DMARD in PsA but has only borderline “symptom modifying” properties. Its value in active PsA is questionable when there are other agents, such as leflunomide and TNF-inhibitors, which are true DMARDs. This has important implications for current national and international guidance for the treatment of PsA.
OBJETIVO: MTX es ampliamente utilizado para el tratamiento de la sinovitis en la APs sin documentos de evidencia juicio. El objetivo de nuestro estudio fue probar el valor de MTX en el primer ensayo controlado con placebo, aleatorizado (ECA) en la artritis psoriásica.
MÉTODOS: A los 6 meses de doble ciego ECA comparó MTX (15 mg / semana) con el placebo en la artritis psoriásica activa. El resultado primario fue criterios de respuesta del PSA (PsARC). Otros resultados incluyeron ACR20, DAS-28 y sus componentes individuales. Los datos que faltaban fueron imputados utilizando múltiples métodos de imputación. Los tratamientos se compararon mediante análisis de regresión logística (ajustado por edad, sexo, duración de la enfermedad y, en su caso, las puntuaciones de referencia individuales).
RESULTADOS: Cuatrocientos sesenta y dos pacientes fueron examinados y 221 contratados. Ciento nueve pacientes recibieron MTX y 112 recibieron placebo. Cuarenta y cuatro pacientes se perdieron durante el seguimiento (21 MTX, 23 placebo). Veintiséis pacientes abandonaron el tratamiento con MTX (14, 12 con placebo). La comparación de MTX con placebo en todos los pacientes asignados al azar a los 6 meses no mostró ningún efecto significativo sobre PsARC [odds ratio (OR) 1,77, 95% CI 0,97, 3,23], ACR20 (OR 2.00, IC 95%: 0,65, 6,22) o DAS-28 ( O 1,70, IC del 95%: 0,90, 3,17). Tampoco se observaron efectos significativos del tratamiento sobre la oferta y el número de articulaciones inflamadas, VSG, PCR, HAQ y el dolor. Los únicos beneficios de MTX es la disminución de los pacientes y evaluador de las puntuaciones globales y las puntuaciones de la piel a los 6 meses (p = 0,03, p <0,001 y P = 0,02, respectivamente). No hubo eventos adversos inesperados.
Conclusiones: Este ensayo de la artritis psoriásica activa no encontró pruebas de MTX mejora de la sinovitis y en consecuencia plantea preguntas acerca de su clasificación como un fármaco modificador de la enfermedad en la artritis psoriásica. el registro de ensayos. Current Controlled Trials, www.controlled-trials.com, ISRCTN: 54376151.
Background: Methotrexate (MTX) is widely used as a disease modifying drug (DMARD) in psoriatic arthritis (PsA) without definitive supporting clinical trial evidence. We tested its effectiveness in the first large multicentre randomised controlled trial (RCT) of MTX in active PsA (MIPA). Methods: A 6-month double-blind RCT compared oral MTX (15mg/week) with placebo in patients with active PsA. The primary outcome measure was the PsA Response Criteria (PsARC); other composite measures included ACR20 and DAS28. We analysed changes in individual measures including “disease modifying” (joint counts, HAQ, ESR and CRP) and “symptom modifying” (global assessments and pain) measures, skin and nail scores. Results: 462 patients were screened and 221 recruited. 71/109 (65%) of those who received MTX and 77/112 (69%) of those who received placebo completed 6 months therapy. 19 patients (11 MTX, 8 placebo) withdrew for toxicity and 22 (8 MTX, 14 placebo) for inefficacy. No significant treatment effects were seen on PsARC, ACR20 and DAS28 at 3 or 6 months using intention to treat logistic regression analysis (including multiple imputations for missing data and adjustment for age and sex). (Figure presented) There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ, pain and nail scores using ordinal linear regression analyses (adjusted for age, sex, baseline scores and disease duration). Patient and physician global scores and skin scores did improve with MTX compared to placebo but at 6 months only (p=0.03, p=0.02 and p=0.02). Separate analysis of polyarticular and oligoarticular PsA subsets also showed no treatment effect for PsARC, ACR20 and DAS28 at 3 or 6 months. Conclusions: Contrary to general opinion, MTX does not act as a DMARD in PsA but has only borderline “symptom modifying” properties. Its value in active PsA is questionable when there are other agents, such as leflunomide and TNF-inhibitors, which are true DMARDs. This has important implications for current national and international guidance for the treatment of PsA.
