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Immunomodulatory Agents for the Treatment of Relapsing Multiple Sclerosis
A Systematic Review
Steven L. Galetta, MD;
Clyde Markowitz, MD;
Andrew G. Lee, MD
Arch Intern Med. 2002;162:2161-2169.
Background Within the past 10 years, several immunomodulatory agents (IMAs) have
become available for the treatment of relapsing multiple sclerosis (MS), making
therapeutic decisions more complex. We performed a systematic review of the
literature to assess the efficacy and safety of these agents on physical,
inflammatory, and cognitive measures of disease activity.
Methods We identified relevant studies by searching electronic databases (MEDLINE
and Current Contents) from January 1, 1993, through August 31, 2001. We included
English-language reports of data from phase 3 trials of interferon beta-1b
(Betaseron), 2 preparations of interferon beta-1a (Avonex and Rebif), or glatiramer
acetate (Copaxone) for the treatment of relapsing MS.
Results Twenty-one studies met explicit inclusion criteria. Comparison of study
results indicated no differences among IMAs regarding their efficacy on relapse-related
measures. Interferon beta-1a significantly reduced disability progression,
whereas no significant effect of glatiramer acetate or interferon beta-1b
on disability progression was seen. On inflammatory measures, all of the IMAs
showed reductions in the burden of disease (T2-weighted lesions) to varying
degrees. Interferon beta and glatiramer acetate reduced new lesion activity;
however, interferon beta had a more profound effect. One interferon beta-1a
preparation (Avonex) appeared to reduce brain atrophy, whereas glatiramer
acetate showed an effect in 1 of 2 studies. Only Avonex demonstrated efficacy
in slowing progression of cognitive dysfunction.
Conclusions Data show that the IMAs have similar effects on several physical and
inflammatory measures. In addition, Avonex has demonstrated efficacy in slowing
cognitive progression in relapsing MS. One disadvantage of interferon beta
is the possibility of immunogenicity, which may occur more often with subcutaneous
administration. The IMAs have similar safety and tolerability profiles.
From the Departments of Neurology (Drs Galetta and Markowitz) and Ophthalmology
(Dr Galetta), University of Pennsylvania Hospital, Philadelphia; and the Departments
of Ophthalmology, Neurology, and Neurosurgery, University of Iowa Hospitals
and Clinics, Iowa City (Dr Lee). Drs Galetta and Markowitz have received research
funding and speaking honoraria from Biogen, Inc, Cambridge, Mass, and Teva
Neuroscience, Kansas City, Mo. Dr Markowitz has received research funding
from Serono, Inc, Norwell, Mass.
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