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)  (see figure 1)
- 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)  (see figure 2)
- stabilized the MRI lesion area (change from baseline to year 2 (N=294): -0.1% vs. 20%, p<0.001) .
Figure 1: Annualized relapse rate in the BETAFERON pivotal RRMS (2-year data) 
Figure 2: 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 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 :
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].
*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.
- The IFNB Multiple Sclerosis Study Group. Neurology 1993; 43(4): 655-61. Return to content
- Paty DW et al. Neurology 1993; 43(4): 662-5. Return to content
- The IFNB Multiple Sclerosis Study Group. Neurology 1995; 45(7): 1277-85. Return to content
- Goodin DS et al. Mult Scler 2019; 25(6): 837-47. Return to content
- Betaseron US prescribing information, November 2021. Available at: https://labeling.bayerhealthcare.com/html/products/pi/Betaseron_PI.pdf Return to content
- BETAFERON European Summary of Product Characteristics, October 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/betaferon-epar-product-information_en.pdf Return to content
- Ebers G et al. Clin Ther 2009; 31: 1724-36. Return to content
- Goodin DS et al. Neurology 2012; 78: 1315-22. Return to content