Comparative effectiveness of interferons in relapsing–remitting multiple sclerosis: a meta-analysis of real-world studies

Abstract

Background: Differences between interferons have been evaluated for over 20 years. While randomized controlled trial (RCT) data is mainly used for assessments and strong data for causal inferences, it does not necessarily reflect everyday practice. Real-world data may provide additional information.

Purpose: To assess the results, quality, and representativeness of observational studies directly comparing interferons (IFNs) in RRMS.

Methods: Medline and Embase were searched for observational studies comparing IFN-beta-1a 30 mcg IM (Avonex¹), IFN-beta-1a 44 mcg SC (Rebif²) and/or IFN-beta-1b 250 mcg SC (Betaseron³). Outcomes included annualized relapse rate (ARR), proportions relapse free, confirmed progression free, treatment persistence, and neutralizing antibodies rates (NABs) measured up to 5 years of treatment. Data was combined using random effects meta-analyses. Categorical values were analyzed using chi-squared and Mann–Whitney tests.

Results: Thirty-six studies examining 32,026 patients (72.5% females, age = 39.2 ± 3.7 years, disease duration = 5.6 ± 2.0 years) were identified. Thirty-three studies investigated IFN-beta-1a IM (N = 11,925), 30 IFN-beta-1a SC (N = 10,684) and 34 IFN-beta-1b SC (N = 9417). Baseline ARRs were similar (1.37 ± 0.35, 1.51 ± 0.27 and 1.55 ± 0.23, respectively; P = .101) as were EDSS scores (2.24 ± 0.39, 2.33 ± 0.30, 2.55 ± 0.38; P = .070) and >75% were naïve to IFNs. On treatment, ARRs were comparable (IFN-beta-1a IM 0.52 ± 0.27, IFN-beta-1a SC 0.51 ± 0.24, IFN-beta-1b SC 0.55 ± 0.23; P = .595). Proportions of relapse-free patients were similar between drugs (P > .05 for all data points), except that IFN-beta-1a SC was superior to IFN-beta-1b SC in years 3–5 (all P ≤ .001). After 1 year, EDSS scores were comparable; after 2 years, IFN-beta-1a IM and IFN-beta-1a SC incurred less disease progression than IFN-beta-1b SC (P < .02). Confirmed progression-free rates and persistence were similar over 5 years. Fewer patients developed NABs with IFN-beta-1a IM (4.7 ± 1.5%) versus IFN-beta-1a SC (21.4 ± 2.8%) (P < 0.001) or IFN-beta-1b SC (32.2% ± 3.3%) (P < .001).

Conclusions: In this comprehensive meta-analysis of real-world studies in RRMS, IFN-beta-1a IM, IFN-beta-1a SC and IFN-beta-1b SC had similar clinical profiles. When selecting an IFN, practitioners should consider observational data in their decision making process.

Keywords:

• Disease progression
• effectiveness
• interferon
• persistence
• relapses
• relapsing–remitting multiple sclerosis

Notes

Transparency

Declaration of funding

Funded by Biogen Inc. T.R.E. and B.G.B. conducted the search, extracted and verified data, wrote and edited the manuscript and approved the final version. M.M. conceived of the project, assisted in the research design, edited/revised it and approved the final manuscript.

Declaration of financial/other relationships

T.R.E. and B.G.B. have disclosed that they received funding from Biogen Inc. for this research. M.M. has disclosed that he is a shareholder and an employee of Biogen Inc.

The CMRO peer reviewer on this manuscript has received an honorarium from CMRO for the review work, but has no relevant financial or other relationships to disclose.

Notes

1 Avonex is a registered trade name of Biogen Inc., Cambridge, MA, USA

2 Rebif is a registered trade name of Serono Inc., Rockland, MA, USA

3 Betaseron is a trade name of Bayer Healthcare Pharmaceuticals Inc., Whippany, NY, USA