Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial.
BACKGROUND
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 with AIED.


METHODS
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 States.


METHODS
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.


METHODS
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).


CONCLUSIONS
Methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED.
Harris
Jeffrey P
JP
Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92103-8895, USA. jpharris@ucsd.edu
Weisman
Michael H
MH
Derebery
Jennifer M
JM
Espeland
Mark A
MA
Gantz
Bruce J
BJ
Gulya
A Julianna
AJ
Hammerschlag
Paul E
PE
Hannley
Maureen
M
Hughes
Gordon B
GB
Moscicki
Richard
R
Nelson
Ralph A
RA
Niparko
John K
JK
Rauch
Steven D
SD
Telian
Steven A
SA
Brookhouser
Patrick E
PE
D001299:Audiometry; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004311:Double-Blind Method; D004427:Ear Diseases / Q000188:drug therapy*; D007758:Ear, Inner; D005938:Glucocorticoids / Q000627:therapeutic use*; D006312:Hearing Loss, Bilateral / Q000188:drug therapy / Q000276:immunology; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008727:Methotrexate / Q000627:therapeutic use*; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011241:Prednisone; D008727:Methotrexate