Researchers have demonstrated that Methotrexate, a promising drug to treat hearing loss in patients with autoimmune inner ear disease (AIED), proved no more effective than placebo in a recently concluded four-year study.
In findings published in the October 8, 2003 issue of the Journal of the American Medical Association (JAMA), a team headed by University of California, San Diego (UCSD) Professor and Chief of Otolaryngology Head and Neck Surgery, Jeffrey Harris, M.D., also noted that the steroid Prednisione proved very effective in both stabilizing and helping over 57% of the AIED patients regain hearing.
"AIED is a rapidly progressive form of sensorineural hearing loss. If left untreated or treated inadequately, AIED can result in profound deafness," says Harris. "We've known for some time that steroids are effective in improving hearing loss in AIED."
However, he noted, the many side effects associated with maintaining prolonged steroid therapy has led to the search for more effective drugs to treat this condition over the long term. And, once the steroids are withdrawn, the hearing loss may reoccur. Methotrexate has been considered a promising drug to treat AIED, due to its long track record as an effective anti-inflammatory, says Harris, improving patients with rheumatoid arthritis, an autoimmune disease that affects the body's joints. Since AIED is also an autoimmune condition, Harris says researchers hoped the drug would have the same therapeutic effect.
AIED starts with the rapid appearance of bilateral, fluctuating and progressive, asymmetrical sensorineural hearing loss. Patients show hearing loss and usually tinnitus. Several blood tests are now being tested to identify patients with AIED. Approximately two-thirds of patients exhibit this autoimmune disease in their ears. In the other third, patients may have some of the well-known rheumatic diseases occurring concurrently with the hearing loss.
"In earlier studies where Methotrexate was used to treat AIED, the initial results appeared positive. The current study was designed to determine in a controlled, double-blind fashion if Methotrexate could maintain the hearing improvement achieved initially with Prednisone," Harris says.
The study enrolled 116 patients with AIED, treating each of them with one month of high dose Prednisone. At the end of the first phase, 67 who showed significant hearing improvement were randomized to receive either Methotrexate or placebo. Prednisone was slowly tapered in both groups over a 3-month period while the Methotrexate and placebo doses were increased.
The results showed that Methotrexate was no more effective than the placebo in maintaining the hearing gain achieved with Prednisone. Of the 67 patients who went on to receive Methotrexate or placebo, 61 were disqualified from continuing the study due to further hearing losses.
Of the 116 patients who received the initial high dose steroids, 63% responded to Prednisone in one ear while 37% responded in both ears, and the researchers observed that long-term Prednisone was well tolerated under the close management of the treating physicians involved in this study.
Harris says the results underscore the importance of well-controlled studies to test the efficacy of drugs in the treatment of AIED, adding it also demonstrates the urgent need to discover more effective and lasting treatments for this condition that usually leads to acute deafness.
The study published in JAMA was sponsored by the National Institute on Deafness and Communication Disorders. Co-authors were Michael H. Weisman, M.D., Cedars-Sinai Medical Center, Los Angeles; Jennifer M. Derebery, M.D., and Ralph A. Nelson, M.D., House Ear Institute, Los Angeles; Mark A. Espeland, PhD, Wake Forest University, Winston-Salem, NC; Bruce J. Gantz, M.D., University of Iowa, Iowa City; A. Julianna Gulya, M.D., National Institute on Deafness and Other Communication Disorders, Bethesda, MD; Paul E. Hammerschlag, M.D., New York University, NYC; Maureen Hannley, PhD, American Academy of Ototlaryngology-Head & Neck Surgery, Alexandria, VA; Gordon B. Hughes, M.D., The Cleveland Clinic, Cleveland, OH, Richard Moscicki, M.D., Massachusetts General Hospital, Boston, MA; John K. Niparko, M.D., Johns Hopkins University, Baltimore, MD; Steven D. Rauch, M.D., Massachusetts Eye and Ear Infirmary, Boston, MA; Steven A. Telian, M.D., University of Michigan, Ann Arbor, MI; and Patrick E. Brookhouser, M.D., Boystown National Research Hospital, Omaha, NE.
Materials provided by University Of California - San Diego. Note: Content may be edited for style and length.
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