April 17, 2002
Serono, S.A. announced yesterday that the 48-week findings from a study comparing Rebif® (interferon beta-1a) to Avonex® (interferon beta-1a) in multiple sclerosis were presented at the annual meeting of the American Academy of Neurology (AAN) in Denver, Colorado.
Hillel Panitch, MD, a University of Vermont College of Medicine researcher for the EVIDENCE (1) Study Group, presented the findings.
"It is very clear from this data that the treatment benefit of Rebif over Avonex in preventing the occurrence of relapses is maintained for 48 weeks," said Dr. Panitch. "This is a highly significant result for physicians and patients in the treatment of multiple sclerosis".
The primary endpoint of the EVIDENCE study was based on a comparison of the proportion of patients who did not experience a relapse of multiple sclerosis (MS) at 24 weeks.
Over 48 weeks, 62 percent of patients who received Rebif did not have a relapse compared to 52 percent of Avonex-treated patients, a statistically significant difference (p=0.009). Rebif patients had a 19 percent relative increase in remaining free of relapses over the 48 weeks compared to Avonex patients. The comparative figure during the first 24 weeks was also 19 percent in favor of Rebif.
Rebif patients had a 30 percent reduction in the rate of occurrence of first relapse during the 48 weeks relative to Avonex patients (p<0.003).
A main endpoint of the study over 48 weeks was an assessment of brain lesions as measured by T2 weighted magnetic resonance imaging (MRI) scans. Patients taking Rebif had significantly fewer active lesions per scan (0.9) than patients taking Avonex (1.4). This relative reduction of 36 percent in favor of Rebif is a highly statistically significant difference (p<0.001). The exact relationship between MRI findings and the clinical status of patients is unknown.
A comparison of safety based on the 48-week results indicates that both Rebif and Avonex are associated with a similar overall side effect profile, including flu like symptoms, headache, fatigue and muscle ache that occur in about half of the patients treated. Consistent with the higher and more frequent dose of interferon used in Rebif therapy, certain side effects were observed in significantly greater number of patients on Rebif than on Avonex: injection site reactions (83 percent versus 28 percent), liver function disorders (18 percent versus 9 percent), and changes in white blood cell counts (11 percent versus 5 percent). These side effects had little impact on the ability of patients to continue on Rebif therapy, and no significant difference was seen in the proportion of patients who stopped therapy due to the events (5 percent versus 3 percent). When considering severe side effects, no difference between patients taking Rebif and Avonex was seen. Moreover, the total proportions of patients who remained on therapy were very similar, with 93 percent of Rebif patients and 94 percent of Avonex patients completing 48 weeks of treatment.
The effect of neutralizing antibodies on the efficacy of treatment with interferon beta-1a is unknown (2). In the EVIDENCE trial, the development of neutralizing antibodies did not have any observable clinical impact and did not affect Rebif's superiority over Avonex in the primary endpoint of preventing relapses.
The EVIDENCE study is the largest prospective, randomised, comparative study of two disease modifying drugs in relapsing-remitting multiple sclerosis (RRMS) to date. The open-label, assessor-blinded study included 677 patients with RRMS who had not been
treated with interferon before, ages 18-55, at 56 centers in the US, Canada and Europe. Patients underwent repeated clinical and MRI assessments while taking either Rebif (44 mcg three times weekly, subcutaneously) or Avonex (30 mcg once weekly, intramuscularly). During the study, assessing neurologists and radiologists were blinded from knowing which drug the patients were taking.
(1) EVIDENCE: Evidence for Interferon Dose-response European-North American Comparative Efficacy.
(2) Goodin DS, Frohman EM, Garmany GP, et al. Disease Modifying Therapies in Multiple Sclerosis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002; 58: 169-178, 175.
SOURCE: Serono, S.A.
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