Methotrexate Not Effective in Maintaining Improvements in Hearing
Gained from Prednisone
October 7, 2003
Bethesda, Maryland --- 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 funded by the National Institute
on Deafness and Other Communication Disorders (NIDCD), one of the
National Institutes of Health (NIH). The study, published in the
October 8 issue of the Journal
of the American Medical Association, was carried out by
the Otolaryngology Clinical Trials Cooperative Group under the auspices
of the American Academy of Otolaryngology-Head and Neck Surgery
Foundation.
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.
"This clinical trial, under the leadership of Jeffrey P. Harris,
M.D., Ph.D., of the University of San Diego, was undertaken to provide
clinicians with important evidence-based guidance for the use of
potentially toxic medications to treat patients with AIED,"
said Patrick E. Brookhouser, M.D., Principal Investigator of the
Otolaryngology Clinical Trials Cooperative Group.
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 NIDCD. "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."
NIDCD supports and conducts research and research training on
the normal and disordered processes of hearing, balance, smell,
taste, voice, speech, and language and provides health information,
based upon scientific discovery, to the public. For more information
on NIDCD programs: www.nidcd.nih.gov.
The American Academy of Otolaryngology-Head and Neck Surgery
(www.entnet.org) represents
the nation's specialist-physicians who diagnose and treat disorders
of the ear, nose, and throat and related structures of the head
and neck.
For more information on the study, contact:
A. Julianna Gulya, M.D., Chief, Clinical Trials, Epidemiology and
Biostatistics Branch, National Institute on Deafness and Other Communication
Disorders, Bethesda, Maryland; 301-435-4085.
Jeffrey P. Harris, M.D., Ph.D., Principal Investigator, AIED Clinical
Trial, Division of Otolaryngology-Head and Neck Surgery, University
of California, San Diego; 619-543-7896.
Patrick E. Brookhouser, M.D., Principal Investigator, Otolaryngology
Clinical Trials Cooperative Group, Boys Town National Research Hospital,
Omaha, Nebraska; 402-498-6510.
Maureen Hannley, Ph.D., Associate Vice President for Research and
Development, American Academy of Otolaryngology-Head and Neck Surgery,
Alexandria, Virginia; 703-519-1547.
Study Statistician
Mark Espeland, Ph.D., P.I. Study Statistician, Clinical Trials
Coordinating Committee, Wake Forest University Medical Center, Winston-Salem,
North Carolina.
* Participating Clinical Centers
Cleveland Clinic Foundation: Gordon B. Hughes, M.D. (Co-Investigator).
House Ear Institute: Jennifer M. Derebery, M.D. (Co-Investigator);
Ralph A. Nelson, M.D.
Johns Hopkins University: John K. Niparko, M.D. (Co-Principal Investigator)
Massachusetts Eye and Ear Infirmary: Richard Moscicki, M.D. (Co-Principal
Investigator); Steven D. Rauch, M.D.
New York University: Paul E. Hammerschlag, M.D. (Co-Principal Investigator)
University of California, San Diego: Jeffrey P. Harris, M.D., Ph.D.
(Principal Investigator, Steering Committee Chair)
University of Iowa: Bruce J. Gantz, M.D. (Co-Principal Investigator)
University of Miami: Thomas J. Balkany, M.D. (Co-Principal Investigator)
University of Michigan: Steven A. Telian, M.D. (Co-Principal Investigator)
University of Texas-Southwestern, Dallas: Peter S. Roland, M.D.
(Co-Principal Investigator)
EMBARGOED FOR RELEASE
October 07, 2003 at 4 p.m. EDT
For additional information, contact:
Mary Sullivan, M.P.A.
Marin P. Allen, Ph.D.
(301) 496-7243.
Top
|
 |
|