Background: The immune system sometimes makes a mistake and produces antibodies that react with the body's own tissues. These are autoantibodies. Some autoantibodies may be directed against the inner ear. If untreated, this may result in rapidly progressive loss of hearing in both ears, ending in deafness. There may also be vestibular symptoms such as vertigo and ataxia (wobbliness). Treatment is aggressive steroid therapy.
The Gist: A clinical trial was underway to see if the antimetabolite drug methotrexate could maintain the hearing of patients with autoimmune inner ear disease who had been successfully treated with the steroid prednisone. Methotrexate failed to maintain hearing. The trial was halted.
Comment: This was an excellent clinical trial and a good example of how negative results are valuable. Methotrexate is not an innocuous drug. The knowledge that methotrexate does not help in this disease will spare patients from being needlessly exposed to it.
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Methotrexate not effective in maintaining improvements in hearing gained from prednisone
Oct 8, 2003 -- Methotrexate is not effective in maintaining hearing in patients with autoimmune inner ear disease (AIED) who had been previously treated with prednisone, according to the results of a multi-center study.The study was published in the October 8 issue of the Journal of the American Medical Association.
AIED is a rare disorder that can result in rapidly progressive hearing loss and deafness if left untreated. Because evidence suggests that an altered immune response may play a role in its development, therapy that targets the immune system is considered the standard of treatment for AIED. A number of treatments have been proposed for long-term management of AIED, but lack scientific validation.
High-dose prednisone is known to reverse hearing loss and maintain hearing, but usually cannot be given for long periods of time. Prednisone in combination with other drugs has been proposed as an effective approach to long-term management of hearing loss due to AIED. Cytotoxic drugs were initially considered but many of these agents can have serious side effects that may result in unacceptable long- term risks, especially in young people.
Methotrexate has been shown to improve hearing and balance in Meniere's disease and other hearing disorders and is generally considered safer and better tolerated than cytotoxic drugs. Evidence from small, uncontrolled studies suggested that methotrexate might be helpful in treating AIED. A randomized, controlled study was needed to determine the drug's potential to maintain hearing achieved with prednisone therapy.
Participants for the study were recruited at 10 tertiary care centers around the country. A prospective, double- blind placebo controlled study was conducted with 67 AIED patients who reported progressive loss of hearing in at least one ear and whose hearing improved after one month of receiving high-dose prednisone.
Study participants were randomized to receive either methotrexate or placebo, while prednisone was slowly tapered in both groups. Final hearing assessment was carried out at 52 weeks to determine each participant's hearing level.
The researchers found that patients in both the methotrexate and placebo groups had similar rates of hearing loss. No significant differences were noted in the two groups with respect to standard measurements of hearing, i.e. pure tone air conduction thresholds and word identification scores.
"This randomized, controlled clinical trial demonstrates that methotrexate is no more effective than placebo in maintaining hearing improvements in patients with AIED who had initial benefit from high-dose corticosteroids," said James F. Battey, Jr., M.D., Ph.D., director of the National Institute on Deafness and Other Communication Disorders, which funded the study. "Recruitment into the study was halted as soon as it became apparent that hearing loss was comparable in both groups."
Dr. Battey adds, "The results of this study clearly underscore the need for more effective and less toxic therapy for AIED, and that randomized, controlled clinical trials are necessary to establish benefit."
Source: National Institutes of Health (www.nih.gov)