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.
OBJECTIVE: To evaluate the efficacy and safety profile of methotrexate (MTX), leflunomide (LEF) and low-dose MTX and LEF (MTX + LEF) combined treatment for psoriatic arthritis (PsA). METHODS: This was a 24 weeks, two-center, open-labeled, controlled trial. All subjects fulfilled the moll and wright criteria for definite PsA. Subjects were given one of the 3 regimens, MTX, or LEF, or MTX + LEF. The primary end point was proportion of psoriatic arthritis response criteria (PsARC) response. The secondary end point was proportion of modified 20% improvement of American College of Rheumatology (ACR20) response. RESULTS: At week 24, the percent of patients achieving PsARC in MTX, LEF and MTX + LEF group were 75.0%, 68.8%, 83.3% respectively, and the percent of patients achieving ACR20 were 66.7%, 50.0%, 83.3% respectively. At week 24, tender joint counts, swollen joint counts, patient's assessment of pain, patient's global assessment (PGA), physician's global assessment, health assessment questionnaire (HAQ) were significantly improved compared with base-line values (P < 0.05). At week 24, the improvement of patient's assessment of pain, HAQ, ESR were better in the MTX + LEF group compared with LEF group while the improvement of patient's assessment of pain, PGA, HAQ, ESR were better in the MTX group compared with LEF group (P < 0.05). The incidence of treatment related adverse events was 38.5%, 38.9% and 35% in MTX, LEF and MTX + LEF group respectively. There was no serious adverse reactions. CONCLUSION: Low dose MTX + LEF regimen showed similar good efficacy and safety profile for PsA patients.
Thirty-five patients with Early Psoriatic Arthritis (EPA) (17 female and 18 male; mean age 25.6 years) entered this randomised 6-month study. At the enrolment, all patients were on non-steroidal anti-inflammatory drug (NSAID) therapy on demand and were divided in two matched groups (A and B). Group A continued NSAID therapy at full dosage in the following 3 months and then added methotrexate (MTX) for another 3 months. Group B was under the combination of NSAID and MTX for the entire 6-month period. Clinical and laboratory assessment included the count of tender joints and/or entheses (TJC), the count of swollen joints and/or entheses (SJC), patient's global assessment (PGA), physician's global assessment (PhGA), patient's assessment of pain (VAS), erythrocyte sedimentation rate (ESR) and serum concentration of C-reactive protein (CRP). All variables were done at baseline (T0), at 3 (T3) and at 6 months (T6). In both group A and in group B, there was a significant improvement of all variables at T3 and T6. However, in comparison to the patients of group A, patients included in group B showed a more rapid and marked improvement of TJC and SJC, which was statistically significant at T3 (p < 0.05). In contrast, the improvement of PGA, PhGA, VAS, ESR and CRP was not significantly different between groups. The early use of MTX in EPA patients markedly improves TJC and SJC. In fact, at T3, other markers used to quantify EPA disease activity, in particular PGA, PhGA, VAS, ESR and CRP, did not show significant differences in EPA patients treated with either NSAIDs or MTX. This finding suggests an incomplete control under MTX of the pathogenetic process and stimulates further interest on early use of other therapeutical approaches capable of modifying the course of disease.
OBJECTIVE: To compare the effectiveness and toxicity of cyclosporin A (CsA) vs low-dose methotrexate (MTX) over a period of one year in the treatment of psoriatic arthritis (PsA) with peripheral involvement.
METHODS: Thirty-five patients with PsA were enrolled in a prospective, controlled, randomized trial. CsA was initially given in doses of 3 mg/kg/day to a maximum permitted dose of 5 mg/kg/day; MTX was given in oral doses of 2.5 mg every 12 hours for 3 consecutive doses each week up to a maximum dose of 15 mg/weekly. Clinical and laboratory evaluations were performed at entry and monthly thereafter.
RESULTS: After 6 and 12 months the number of painful joints, the number of swollen joints, the Ritchie index, the duration of morning stiffness, grip strength, CRP, the patient's and the physician's assessment of PsA activity, as well as the PASI, were significantly improved in both treatment groups. ESR values were significantly reduced only in the MTX group (p < 0.01), which also showed a significantly increase of liver enzymes. The changes in the main clinical and laboratory parameters during the course of CsA or MTX treatment were not significantly different except for the AST and ALT levels (p < 0.05). After one year of therapy CsA and MTX were withdrawn in 41.2% and 27.8% of the patients respectively, but these differences were not statistically significant.
CONCLUSION: Our one-year prospective trial shows that low-dose CsA and MTX are both effective in the treatment of PsA, but the differences in the tolerability of these drugs must be considered at the start of therapy.
Overall 126 patients with verified and clinically active psoriatic arthritis (PA) were subjected to a randomized study of the efficacy of chrisanolum (Chr), sulfasalicylic drugs (SSD) (sulfasalazine and salazopyridazine) and methotrexate (MT) as compared to nonsteroidal anti-inflammatory drugs (NSAID). The treatment that lasted for a year was completed by 77 patients: in the group on NSAID, by 31, on Chr by 15, on SSD by 15, and on MT by 16. In the remainder, the treatment was discontinued because of side effects. The best clinical effect was recorded in patients on Chr. The improvement was observed in 73% of the patients, with a significant effect being attained in 60%. In the groups on SSD and MT, the improvement was observed in 80 and 69%, respectively. However, noticeable improvement was only recorded in 20 and 19%. SSD turned out more effective than MT. in the group on NAID, the improvement was ascertained but in 35% of the patients, with noticeable one being attained in 6%. According to Pearson's criterion chi 2, the results of the treatment with NAID alone were less potent than in the group given Chr (p < 0.001) and SSD (p < 0.05). The differences between the effect of the treatment with NAID and MT appeared nonsignificant (p > 0.1). Therefore, according to the diminution of the clinical efficacy in PA, the basic drugs may be distributed in the following way: Chr, SSD, MT. The side-effects in the group on NAID were. recorded in 37% of cases, in the group on Chr in 53%, on SSD in 33%, and on MT in 55%. This means that SSD were tolerated best of all.
Treinta y siete pacientes con artritis psoriásica se introdujeron en una de 12 semanas de estudio prospectivo, controlado, multicéntrico, doble ciego y comparativo con placebo y la terapia oral de pulso metotrexato. El metotrexato se administró en una dosis de 2,5-5,0 mg cada 12 horas en 3 dosis consecutivas por semana. Un programa de fondo estable de medicamentos con fármacos antiinflamatorios no esteroideos se le permitió. El metotrexato fue superior al placebo sólo en la evaluación del médico de la actividad de la artritis y en la mejora de la cantidad de área de superficie de la piel con psoriasis. Un aumento pequeño pero estadísticamente significativo de la bilirrubina sérica total se produjo en los pacientes tratados con metotrexato. Ninguno de los pacientes se retiraron del estudio por efectos adversos del fármaco.
