BETAFERON in relapsing-remitting MS (RRMS): The pivotal study
The pivotal BETAFERON study was the first larger phase 3 study conducted in MS [1-3]. The study evaluated the efficacy and safety of BETAFERON in established MS and led to the approval of BETAFERON in RRMS. The BETAFERON pivotal study was a multicenter, randomized, double-blind, placebo-controlled trial in 372 ambulatory patients with RRMS. The study duration was up 5 years. The study had three arms: interferon beta-1b 250 μg (approved dose of BETAFERON), interferon beta-1b 50 μg (not an approved dose) and placebo. The primary endpoints of the trial examined differences in relapse rates and the proportion of patients remaining relapse-free between interferon beta-1b and placebo. Safety was also evaluated.
Patients in this trial had well-established, clinically definite MS. Patients had an average duration of MS of 8.05 years (4.4 years since diagnosis), the mean EDSS score* was 2.9 and the mean annualized relapse-rate† over the previous 2 years was 1.68 [1,4]
The 2-year results showed that compared to placebo, treatment with BETAFERON (interferon beta-1b 250 μg) 
- significantly reduced the annual relapse rate (0.84 vs. 1.27, p< 0.0001)  (see figure)
- significantly increased the proportion of patients who were relapse-free (31% vs. 16%, p=0.007) 
- significantly reduced the rates of moderate to severe relapses (0.23 vs. 0.45, p=0.002) 
- stabilized the MRI lesion area (change from baseline to year 2 (N=294): -0.1% vs. 20%, p<0.001)  (see figure)
Annualized relapse rate in the BETAFERON pivotal RRMS (2-year data) 
Annualized rate of moderate and severe relapses in the BETAFERON pivotal RRMS study (2-year data) 
Adverse events significantly associated with BETAFERON treatment were flu-like symptoms and injection site reactions [1,5,6]. Laboratory abnormalities included mild intermittent hypothermia, mild neutropenia, anemia, thrombocytopenia, and mild or moderate liver enzyme (SGPT and SGOT) elevations [5,6].
Despite the absence of strategies like dose-titration and use of autoinjectors to mitigate interferon beta-typical adverse events, flu-like symptoms and injection decreased over time :
See the most up-to-date recommendations for mitigating interferon beta-typical adverse events.
Patients included in the original BETAFERON pivotal study were reanalyzed 16 and 21 years later (cross-sectional data) [7,8].
* EDSS: Kurtzke Expanded Disability Status Scale; the EDSS score is a method of quantifying disability in patients with MS ranging from 0 (normal neurologic exam) to 10 (death due to MS).
† An exacerbation was defined as the appearance of a new clinical sign/symptom or the clinical worsening of a previous sign/symptom (one that had been stable for at least 30 days) that persists for a minimum of 24 hours.
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