Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

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Rudick R., Stuart W., Calabresi P., Confavreux C., Galetta S., Radue E., ...More

NEW ENGLAND JOURNAL OF MEDICINE, vol.354, no.9, pp.911-923, 2006 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 354 Issue: 9
  • Publication Date: 2006
  • Doi Number: 10.1056/nejmoa044396
  • Page Numbers: pp.911-923



Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite
interferon beta therapy, many patients have relapses. Natalizumab, an α4 integrin
antagonist, appeared to be safe and effective alone and when added to interferon
beta-1a in preliminary studies.
We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had
had at least one relapse during the 12-month period before randomization to receive
continued interferon beta-1a in combination with 300 mg of natalizumab (589
patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks.
The primary end points were the rate of clinical relapse at 1 year and the cumulative
probability of disability progression sustained for 12 weeks, as measured by the
Expanded Disability Status Scale, at 2 years.
Combination therapy resulted in a 24 percent reduction in the relative risk of sustained
disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61
to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression
at two years were 23 percent with combination therapy and 29 percent with
interferon beta-1a alone. Combination therapy was associated with a lower annualized
rate of relapse over a two-year period than was interferon beta-1a alone (0.34
vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T2-weighted magnetic
resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination
therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema.
Two cases of progressive multifocal leukoencephalopathy, one of which was fatal,
were diagnosed in natalizumab-treated patients.
Natalizumab added to interferon beta-1a was significantly more effective than interferon
beta-1a alone in patients with relapsing multiple sclerosis. Additional research
is needed to elucidate the benefits and risks of this combination treatment.
( number, NCT00030966.)