Risk factors associated with the cumulative survival of low-dose methotrexate in 273 Japanese patients with rheumatoid arthritis. Durability of treatment with methotrexate in Venezuelan patients with rheumatoid arthritis. [A short-term randomized controlled study with methotrexate in rheumatoid arthritis]. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial. Adverse experience with methotrexate during 176 weeks of a longterm prospective trial in patients with rheumatoid arthritis. Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. A multicenter randomized placebo-controlled trial.
Methotrexate (MTX) has become the most commonly prescribed disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). In the Western countries, the MTX dosage is safely increased to a maximum of 25 mg/wk until a significant response is observed. On the contrary, in Japan, MTX has been approved only as a second-line agent, and the approved maximum MTX dosage is only 8 mg/wk. This suboptimal dosage may affect MTX survival in Japanese RA patients.
                To study risk factors associated with the cumulative survival of MTX in Japanese RA patients.
                Data on 273 patients (male 44, female 229) with RA treated with MTX between January 1, 2000 and September 30, 2004 in our center were studied.
                Two hundred seventy-three patients were followed for 437 person-years of MTX exposure. Mean MTX dosage was 5.5 +/- 1.9 mg/wk. The cumulative MTX survival probability after 5 years was 61.9%. Univariate Cox regression analysis showed a significant correlation between MTX survival probability and use of fewer previous DMARDs, higher dose of MTX, inclusion of folate supplementation, and shorter disease duration. In the multivariate Cox regression model, use of fewer previous DMARDs remained significantly related to MTX survival. Reasons for discontinuation included adverse effects in 34 patients (12.5%) and inefficacy in 6 patients (2.2%).
                Cumulative survival was the same or slightly better than those in reports from Western countries, with less withdrawals reported due to adverse events or inefficacy. Whether these results are due to different MTX needs in Japanese or to acceptance of less clinical efficacy will require further studies. The use of fewer previous DMARDs was associated with longer MTX survival. A multicenter, national, retrospective, and cross-sectional study of 219 hospital-based Venezuelan patients with rheumatoid arthritis (RA) was aimed to evaluate the probability of continuity of treatment with oral methotrexate (MTX). Treatment survival decreased from 92% at 12 months to 42% at 180 months, as assessed by life table analysis and the Kaplan-Meier method. Forty-seven patients stopped treatment and adverse effects (29.7%) and lack of continuous access to medication (19.1%) were the most common causes for withdrawal. MTX survival was decreased in the group with combined MTX plus leflunomide therapy, as shown by the log-rank test. Venezuelan patients with RA have a probability of continuing treatment with oral MTX comparable to non-Hispanic patient populations. However, concomitant use of leflunomide may increase the risk of interruption of MTX treatment in this RA population. Randomized, controlled and double-blind study of 36 patients aimed at the evaluation of the efficacy and toxicity of MTX in the treatment of rheumatoid arthritis. Twenty-eight patients completed the study period: 14 in the MTX group and 14 in the placebo group. The patients treated with MTX presented a statistically significant improvement (p < 0.05) in pain, grip strength and functional ability when compared to placebo treated patients. Mild adverse effects were observed in 4 patients treated with MTX and in 2 patients treated with placebo. These findings support other studies and give to methotrexate a relevant position in the treatment of rheumatoid arthritis, owing to its convenient posology, beneficial effectivity and favourable toxicity. To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX).
                A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy.
                Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy.
                In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks. One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity. To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA).
                Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups.
                One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations.
                Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment. To evaluate the efficacy and safety of methotrexate (MTX) compared with placebo in patients with active ankylosing spondylitis (AS).
                This 24 week, double bind, randomized, placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS. The primary outcome measure was a composite index of improvement in 5 of the following scales: severity of morning stiffness, physical well being, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and physician and patient global assessment of disease activity.
                Seventeen patients received MTX and 18 placebo. In the intention-to-treat analysis at 24 weeks, 53% of patients in the MTX group had a treatment response, compared with 17% in the placebo group (p = 0.03). We observed significant improvements with MTX in physical well being (p = 0.009), BASDAI (p = 0.02), BASFI (p = 0.02), physician global assessment (p < 0.001), patient global assessment (p = 0.03), and HAQ-S (p = 0.02). In the adjusted analysis only MTX determined the improvement in the primary outcome. At the end of the trial, one patient with MTX withdrew due to a lack of compliance, and one with placebo due to a lack of efficacy. We did not observe significant differences in rates of side effects between the 2 groups.
                MTX is safe and effective for patients with AS. Longterm studies are needed to evaluate the permanence of its benefit. Adverse experience occurred with a high frequency in a longterm (greater than 3 years), prospective, double blind, followed by an open trial of methotrexate (MTX) therapy in 45 patients with rheumatoid arthritis (RA). Adverse experiences occurred in 96% of patients, and the discontinuation rate was 44% over 176 weeks. No hepatic or pulmonary fibrosis occurred. Unusual toxicities included weight loss (2 patients), systemic fungal infections (2 patients), and transient noncirrhotic ascites (1 patient). Baseline white blood cell counts and creatinine may help predict adverse experiences. The full dose-toxicity spectrum of MTX RA is not yet fully defined. To compare the efficacy of the combination therapy Methotrexate (MTX) and Chloroquine (CHLO) with MTX and Placebo (PLA) in the treatment of Rheumatoid Arthritis. A total of 82 patients with Rheumatoid Arthritis (RA), diagnosed according to the American College of Rheumatology criteria, received orally either MTX 7.5 mg/week and CHLO 250 mg/day or MTX 7.5 mg/week and PLA 1 tablet/day. Adverse effects (AE) were monitored monthly and disease activity was assessed at 0, 2, 4 and 6 months. Sixty-eight patients completed the study. All outcome measures improved significantly in both treatment groups. Patients receiving MTX/CHLO ended the study with a significantly lower joint count, greater grip strength and better functional ability the patients in the MTX/PLA group, respectively; 4.5 vs 7.5 (P < 0.05), 113.3 vs 89.1 (P < 0.05) and 0.636 vs 0.811 (P < 0.05). Mild AE were more frequently observed in the MTX/CHLO, 17 events in 15 patients, compared to 9 events in 8 patients in the MTX/PLA group (NS). These data indicate that MTX/CHLO is slightly more efficacious and toxic than is MTX/PLA in the treatment of RA.
MTX has a substantial clinical and statistically significant benefit compared to placebo in the short term treatment of people with RA although its use is associated with a high withdrawal rate due to adverse events.