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Commonly Used Drug, Methotrexate, Shown Ineffective in Treating Autoimmunity in Inner Ear Disease

Background: Autoimmune inner ear disease (AIED) is a relatively rare disorder that causes potentially reversible bilateral, rapidly progressive, hearing loss and/or dizziness. Left untreated, this condition can lead to total deafness. Glucocorticoids, powerful anti-inflammatory steroids, have been the most common treatment of AIED, usually resulting in the restoration of some hearing. Unfortunately, long-term use of these drugs is associated with significant side effects. Encouraged by the success of methotrexate, an immunosuppressive drug used to treat rheumatoid arthritis and cancer, doctors have been using methotrexate as a substitute for long term treatment with glucocorticoids for approximately the past five years. Until now, there has been no controlled study to compare the benefits and hearing improvements of methotrexate with those of glucocorticoids.

Advance: NIDCD-supported scientists have undertaken a clinical study to determine whether methotrexate is effective in the treatment of AIED. The trial is a double-blind, randomized, placebo controlled, phase 3 clinical trial. Ten study sites spanning the continental United States participated in the trial. Using the largest prospectively enrolled cohort of individuals with AIED, the study showed that methotrexate was not effective in maintaining hearing recovery in individuals with AIED who had been previously treated with high-dose glucocorticoids.

Implications: More studies are needed to develop and rigorously evaluate effective (and ideally less toxic) therapies for AIED using randomized, controlled clinical trials.

Harris JP, Weisman MH, Derebery JM, Espeland MA, Gantz BJ, Gulya AJ, Hammerschlag PE, Hannley M, Hughes GB, Moscicki R, Nelson RA, Niparko JK, Rauch SD, Telian SA, Brookhouser PE.Treatment of Corticosteroid-Responsive Autoimmune Inner Ear Disease with Methotrexate. JAMA 290: 1875-1883, 2003.