Benefit of Methotrexate as Adjunctive Treatment for Giant Cell Arteritis Confirmed
A study in the August issue of Arthritis & Rheumatism (2007;56:2789-2797) looked at individual patient data from three placebo-controlled trials testing the effectiveness of methotrexate (MTX) as an adjunctive treatment for giant cell arteritis (GCA). This meta-analysis found that, when given in addition to standard corticosteroid treatment, MTX lowers both the risk of GCA relapse and the amount of corticosteroids needed.
Corticosteroids like prednisone are currently the primary option for treating GCA, a vascular disease characterized by inflammation of large arteries, usually in the head, that plagues fewer than 200,000 Americans. If left untreated, GCA can cause headaches, pain and stiffness, and even blindness.
Corticosteroids, given at first in high doses and then tapered down over several months, are “an extremely effective therapy” for GCA, says Peter A. Merkel, MD, MPH, director of the Boston University Vasculitis Center and lead author of the new study. “The critical problem is that they have significant toxicity, especially in the elderly,” he explains.
Indeed, for 53% to 86% of GCA patients, corticosteroids induce serious side effects like mood changes, weight gain, cataracts, and osteoporosis.
Several clinical trials have tested the use of low-dose MTX as an adjunctive treatment for patients with new-onset GCA. But the three largest randomized, placebo-controlled trials came to different conclusions: One showed a clear benefit of using MTX in reduction of GCA relapse and reduced use of corticosteroids; one showed mixed results; and one showed no clear benefit.
These discrepancies led to “great variation within the rheumatology practice community as to the use of MTX,” says Dr. Merkel. Because MTX has its own potential side effects, including liver toxicity, bone marrow toxicity, and GI upset, many doctors were cautious about prescribing it to their elderly patients. The meta-analysis of combined data from the three studies aimed to resolve these discrepancies.
At least one author from each of the three studies was involved in the new study, which pooled comprehensive data – including the time to first relapse, time to second relapse, cumulative dose of corticosteroids, time to discontinuation of corticosteroids, and adverse events – from 161 patients. Using the original data from individual patients, rather than that published in summary tables, “provided for much more sophisticated analyses and more precise estimates of outcomes,” says Dr. Merkel.
The analysis found that after 48 weeks of treatment, patients who received MTX and corticosteroids had a 63% chance of first relapse and 22% chance of second relapse. Patients receiving a placebo and corticosteroids had a significantly higher risk of both first and second relapse – 80% and 40%, respectively.