Context A number of therapies have been proposed for the long-term management
of corticosteroid-responsive, rapidly progressive, bilateral sensorineural
hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged
as the benchmark agent but has not been rigorously evaluated for hearing improvement
in patients with AIED.
Objective To assess the efficacy of long-term methotrexate in maintaining hearing
improvements achieved with glucocorticoid (prednisone) therapy in patients
Design, Setting, and Participants A randomized, double-blind, placebo-controlled trial conducted from
February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive,
bilateral sensorineural hearing loss at 10 tertiary care centers in the United
Intervention Randomization to either oral methotrexate (15 to 20 mg/wk; n = 33) or
placebo (n = 34), in combination with an 18-week prednisone taper. Follow-up
examinations, including audiometric evaluation, were performed at 4, 8, 12,
24, 36, 48, and 52 weeks, or until hearing loss was documented.
Main Outcome Measure Maintenance of hearing improvement achieved from prednisone treatment.
Results Sixty-seven patients (57.8%) enrolled in the prednisone challenge experienced
hearing improvement. Twenty-five patients (37%) experienced hearing improvements
in both ears. Of the individuals who reached study end points, 24 (80%) of
30 end points were because of measured hearing loss in the methotrexate group
and 29 (93.5%) of 31 end points were because of measured hearing loss in the
placebo group (P = .15). Methotrexate was no more
effective than placebo in maintaining the hearing improvement achieved with
prednisone treatment (hazard ratio, 1.31; 95% confidence interval, 0.79-2.17; P = .30).
Conclusion Methotrexate does not appear to be effective in maintaining the hearing
improvement achieved with prednisone therapy in patients with AIED.