Fran Lowry

May 17, 2012

May 17, 2012 (Fort Lauderdale, Florida) — Mycophenolate mofetil (MMF) is superior to methotrexate for the treatment of ocular inflammatory diseases, according to a study presented here at the Association for Research in Vision and Ophthalmology 2012 Annual Meeting.

Using a marginal structural model to simulate a clinical trial comparing the 2 agents, the researchers, led by John H. Kempen, MD, PhD, director of the ocular inflammation service at the Scheie Eye Institute, University of Pennsylvania, in Philadelphia, found that "corticosteroid-sparing" (i.e., complete control of inflammation on prednisone 10 mg/day or less, sustained for at least 30 days) was achieved more rapidly with MMF than with methotrexate.

"While the method we used is not a perfect substitute for a randomized clinical trial, until such a trial can be done, these results provide a reasonably robust evidence base indicating that mycophenolate mofetil is superior to methotrexate in achieving corticosteroid-sparing goals," Dr. Kempen told Medscape Medical News.

"It seems to work considerably faster, which is an important advantage, given the side effects that prolonged systemic corticosteroid therapy can have," he said.

To manage uveitis and other forms of ocular inflammation, ophthalmologists have borrowed the rheumatologic paradigm of using what rheumatologists call 'disease-modifying antirheumatic drugs'," Dr. Kempen explained.

"We have borrowed most of these drugs from rheumatology or transplant medicine, but we have not had the benefit of clinical trials to provide an evidence base to guide our use of these drugs," he said.

He and his team sought to provide the next best possible evidence on the relative effectiveness of the immunosuppressive agents MMF and methotrexate.

The researchers used a marginal structural model, a new statistical method, to simulate a clinical trial comparing the 2 agents with data they had collected in a retrospective cohort study of 613 patients — the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) study.

They found that MMF was statistically significantly superior to methotrexate in controlling ocular inflammation, and that it got oral corticosteroid therapy down to an equivalent of prednisone 10 mg/day or less.

The incidence of corticosteroid-sparing success was lower for methotrexate than for MMF (hazard ratio, 0.65; 95% confidence interval, 0.44 to 0.95).

Corticosteroid-sparing occurred in less than 6 months for about two thirds of MMF-treated patients, although sometimes treatment success took more than 12 months.

There was no substantial variation in the effects of treatment between MMF and methotrexate by site of inflammation (anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, or other sites of ocular inflammation). Discontinuation rates were similar in the 2 treatment groups.

"My perspective on the results is that mycophenolate is preferred unless there is a specific reason to use methotrexate. The results do not suggest that methotrexate is of no use, they just suggest that mycophenolate works better, or perhaps only faster," Dr. Kempen said.

He added that methotrexate is "substantially less expensive than mycophenolate mofetil. In typical therapeutic regimens, methotrexate is taken once weekly, either orally or by subcutaneous injection, whereas mycophenolate mofetil is taken twice daily by mouth on an empty stomach."

The study was supported by the National Eye Institute, National Institutes of Health, Research to Prevent Blindness, Mackall Foundation, and the Department of Veterans Affairs. Dr. Kempen reports a financial relationship with Alcon.

Association for Research in Vision and Ophthalmology (ARVO) 2012 Annual Meeting: Abstract 4169. Presented May 9, 2012.

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