February 14, 2003
Professional Resource Center, The National Multiple Sclerosis Society
A published review of select clinical trials of interferons to treat relapsing-remitting forms of multiple sclerosis concluded that benefit of these immune-modulating therapies beyond one year is unclear because of issues related to the way the studies were designed and reported (February 15, 2003 issue of The Lancet, vol. 361; 545-552). The review also suggests that better clinical trials are needed to accurately assess the long-term effectiveness of these immune-modulating therapies.
There are currently three interferon products approved in the U.S. and other countries for treating persons with relapsing forms of MS: interferon beta-1a (Avonex,® Rebif®) and interferon beta-1b (Betaseron®). The study did not review the effectiveness of two other disease-modifying agents approved in the U.S. and elsewhere, Copaxone® (glatiramer acetate, an immune modulator), and Novantrone® (mitoxantrone, an immune suppressant), because they are not interferons.
The authors, led by Dr. Graziella Filippini (National Neurolgical Institute “C Besta” in Milan, Italy) considered a total of 24 clinical trials of interferons alpha and beta in MS before selecting seven, lasting up to two years, to conduct a systematic “meta-analysis” of published results. Their review included patients with relapsing-remitting MS. Because of differences in the way the reviewed studies were designed and reported, the review was unable to examine the drugs’ impact on the same clinical measures across all seven trials.
By combining the results of five out of the seven trials, the authors verified the benefit of interferons over the course of one year to reduce the number of patients experiencing an exacerbation (attack). Due to a variety of issues related to the design of the studies and because of the number of patients who dropped out of the studies, the authors were unable to adequately review the question of therapeutic benefit beyond the first year of the trials.
The pivotal clinical trials that led to the approvals of interferons here and abroad by multiple regulatory agencies, including the U.S. Food and Drug Administration, were carefully analyzed by those agencies for benefit and safety. In approving these drugs, the FDA determined that they were safe and significantly more effective than placebo for treating relapsing forms of MS. Among the key benefits considered by regulators in the various interferon beta trials were changes in MRI-detected brain lesions, reductions in the frequency and severity of attacks, and reductions in disease progression and disability.
According to Dr. Aaron Miller, Chief Medical Officer for the National MS Society, “The Lancet article highlights issues related to clinical trial design, of which many researchers in the MS field are well aware. It does not provide evidence that interferons do not work after one year, but rather emphasizes the need for longer-term studies and more consistent clinical trial design.
In the current absence of definitive, longer-term studies, patients doing well on interferon therapy are strongly advised to continue treatment as well as regular consultations with a physician knowledgeable about MS,” Dr. Miller concludes.
The Medical Advisory Board of the National MS Society recommends initiation of therapy with an immunomodulator such as interferon beta or Copaxone as soon as possible following a definite diagnosis of MS with a relapsing course, and may be considered for selected patients with a first attack who are at high risk for MS.
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© 2003 The National Multiple Sclerosis Society