SAN FRANCISCO – Methotrexate is not a disease-modifying antirheumatic drug in psoriatic arthritis, despite how well it works in psoriasis, according to Dr. Christopher T. Ritchlin.
Methotrexate is the most widely used drug in the world for psoriatic arthritis (PsA), based on almost no supporting evidence. There have been only two published double-blind, randomized, controlled trials of methotrexate in PsA done over the last 20 years, and both were underpowered and used a low dose of methotrexate (10 mg/week), said Dr. Ritchlin, professor of medicine and director of the clinical immunology research center at the University of Rochester (N.Y.).
A still-unpublished study that was presented at the annual meeting of the American College of Rheumatology in 2010 showed that methotrexate was not more effective than placebo in PsA (Arthritis Rheum. 2010:62 [suppl.]:S277, abstract 664). The study involved 221 patients who were given 15 mg/week of methotrexate or placebo for 6 months. About 65% of subjects in each group dropped out. The primary outcome measure was the psoriatic arthritis response criteria (PsARC), which most rheumatologists do not think is a good outcome measure, Dr. Ritchlin said at the Perspectives in Rheumatic Diseases 2011 meeting.
At the end of 3 and 6 months of the study, there were no differences between methotrexate and placebo on the PsARC, the ACR 20 (the American College of Rheumatology scale based on a 20% improvement in certain parameters), the DAS28 (Disease Activity Score based on a 28-joint count), a sensitive joint count, a tender joint count, and the C-reactive protein level/erythrocyte sedimentation rates. Only the patient and physician global scores and the skin score showed significant improvement in the methotrexate group.
Methotrexate is the most widely used drug in the world for psoriatic arthritis (PsA), based on almost no supporting evidence.
Another unpublished study, conducted in the former Soviet Union and presented at the ARC’s annual meeting in 2009, showed the opposite. The researchers compared infliximab vs. methotrexate in methotrexate-naive patients. The dosage used was 15-20 mg/week. They found that 66% of the patients achieved an ACR 20 improvement on methotrexate alone, as did 86% of those on methotrexate plus infliximab. Remissions according to the DAS28 were reported in 30% of those on methotrexate and in 69% of those on combination therapy.
Although it may be possible to find methotrexate-naive patients in the former Soviet Union, such patients are much less likely to walk into their rheumatologist’s office in the West.
Indirect data supporting the inefficacy of methotrexate come from NOR-DMARD. These data show that 6 months of treatment with a tumor necrosis factor inhibitor (146 patients) had significantly greater beneficial effects on patients with PsA than did methotrexate (356 patients) (Ann. Rheum. Dis. 2007;66:1038-42).
The propensity toward liver disease is another reason not to use methotrexate in patients with PsA, said Dr. Ritchlin at the meeting, which was sponsored by Skin Disease Education Foundation. Methotrexate is hepatotoxic. Data on the findings of 169 liver biopsies that were done on 71 patients with psoriasis showed that methotrexate significantly increased the risk for stage 3 or 4 fibrosis. The risk was highest in obese patients or those with diabetes (J. Hepatol. 2007;46:1111-8).
These findings serve to support "my own bias that this is due to their fatty livers," which have developed as a consequence of their obesity, a common comorbidity in PsA, he said. Another cause of fatty liver in this population may be the metabolic syndrome that often develops in patients with psoriasis.
Dr. Ritchlin reported financial relationships with Abbott, Amgen, Centocor, Genentech, Targacept, UCB, and Wyeth. SDEF and this news organization are owned by Elsevier.