BETAFERON in 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 relapsing-remitting MS (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) [1,2]

  • significantly reduced the annual relapse rate (0.84 vs. 1.27, p= 0.0001) [1] (see figure 1)
  • significantly increased the proportion of patients who were relapse-free (31% vs. 16%, p=0.007) [1]
  • significantly reduced the rates of moderate to severe relapses (0.23 vs. 0.45, p=0.002) [1] (see figure 2)
  • stabilized the MRI lesion area (change from baseline to year 2 (N=294): -0.1% vs. 20%, p<0.001) [2].



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Figure 1: Annualized relapse rate in the BETAFERON pivotal RRMS (2-year data) [1]

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Figure 2: Annualized rate of moderate and severe relapses in the BETAFERON pivotal RRMS study (2-year data) [1]


Adverse events significantly associated with BETAFERON treatment were flu-like symptoms and injection site reactions [1,5,6]. Laboratory abnormalities included mild intermittent lymphopenia, 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 [3]:


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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].



Return to 'Betaferon clinical studies'



*The recommended dose of Betaferon is 250 μg (8.0 million IU), contained in 1 ml of the reconstituted solution, to be injected subcutaneously every other day.

† EDSS: Kurtzke Expanded Disability Status Scale; the EDSS score is a method of quantifying disability in patients with MS ranging from 0 (normal neurological 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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  • Betaseron US prescribing information, November 2021. Available at: Return to content
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