CHICAGO – Glucocorticoids remain the cornerstone of therapy for giant cell arteritis, but aspirin and methotrexate can be useful as adjunctive therapies.
Infliximab, however, does not appear to be of benefit in this disease, said Dr. Philip Seo at a symposium sponsored by the American College of Rheumatology.
Dr. Philip Seo
The benefits of aspirin were demonstrated in a 2004 retrospective study of 175 patients with giant cell arteritis (GCA), including 36 who were being treated with 100 mg/day of aspirin from the time of diagnosis and 139 who were not (Arthritis Rheum. 2004;50:1332-7). Aspirin was shown to be associated with a reduced risk of cranial ischemic events, including acute vision loss and cerebrovascular accident, said Dr. Seo, codirector of the vasculitis center at the Johns Hopkins University, Baltimore.
In that study, only 8% of patients who were treated with aspirin, compared with 29% of those not treated with aspirin, experienced a cranial ischemic event, and that was despite the fact that cerebrovascular risk factors were present in 38.9% and 20% of patients, respectively. In 166 patients from the study who were followed for at least 3 months, the findings were similar: In all, 2.7% of 73 patients treated with aspirin, compared with 12.9% of those not treated with aspirin, experienced a cerebral ischemic event during follow-up, despite 28.8% and 12.9% in the groups, respectively, having cerebrovascular risk factors.
Methotrexate has also been shown to provide some benefit as an adjunctive therapy in GCA, but the effect in studies has been modest at best, and treatment has been disappointing in practice, Dr. Seo said.
Three randomized, double-blind, placebo-controlled trials of methotrexate in this disease had three different results. A meta-analysis of the findings suggested that methotrexate reduced the probability of a first relapse modestly (hazard ratio, 0.65) during nearly 55 weeks of follow-up, and showed that it also reduced the corticosteroid cumulative dose by more than 800 mg on average over 48 weeks (Arthritis Rheum. 2007;56:2789-97). That reduction, however, was not associated with a reduction in steroid side effects, he said.
Still, the beneficial effects are more promising than those seen with infliximab, which has not been found to have benefit in GCA. In fact, a randomized, placebo-controlled, phase II trial that was scheduled to run for about 1 year closed after only 22 weeks because of lack of efficacy in the treatment group, Dr. Seo noted (Ann. Intern. Med. 2007;146:621-30).
Patients in that trial received prednisone/prednisolone and either placebo or 5 mg/kg infliximab infusions. The infusions were given at baseline and were planned for weeks 2, 6, 14, 22, 30, 38, and 46 (with prednisone tapering after randomization in both groups). At the time the study was discontinued, no difference was seen in the proportion of relapse-free subjects, time to first relapse, or cumulative prednisone dose between the two groups.
The findings were somewhat surprising, given that infliximab works so well for so many other forms of large vessel vasculitis, Dr. Seo said.
"Despite the fact that it should work, it doesn’t seem to for GCA," he said.
So for now, the best bet for adjunctive treatment in GCA is aspirin, which "seems to be a very good idea," he said, noting that although it is not yet the standard of care, it may eventually become so.
Methotrexate can be considered as an adjunctive therapeutic option based on the available data, but it has only a small impact, and the question of whether it should be standard remains controversial. Infliximab is "hard to recommend" in GCA, he said adding that the search continues for effective treatments.
Drugs under investigation for GCA include abatacept and tocilizumab, but it remains too early to say if these will be helpful, he noted.
Dr. Seo disclosed that he has received consulting fees and other remuneration from Genentech.