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Subcutaneous Recombinant Interferon-β-1a (Rebif®)

A Review of its Use in the Treatment of Relapsing Multiple Sclerosis

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Abstract

Subcutaneous recombinant interferon-β-1a (SC IFNβ-1a) [Rebif®] is indicated as monotherapy for the prevention of relapses and progression of physical disability in patients with relapsing multiple sclerosis (MS). This article reviews the efficacy and tolerability of SC IFNβ-1a in this indication, with further discussion of its pharmacological properties and pertinent pharmacoeconomic studies.

SC IFNβ-1a efficacy and tolerability were evaluated in randomized, double-blind, multinational trials in patients with relapsing-remitting MS (RRMS). Its efficacy was demonstrated in the 2-year PRISMS trial, as SC IFNβ-1a 22 or 44 µg three times weekly (tiw) significantly reduced relapse rates, with an ≈30% relative risk reduction compared with placebo. SC IFNβ-1a was also associated with significantly delayed progression of disability, and lower disease activity according to MRI, relative to placebo. In the 24-week EVIDENCE trial, a significantly higher proportion of SC IFNβ-1a 44 µg tiw than intramuscular IFNβ-1a (Avonex®) 30 µg once weekly recipients remained relapse free. A serum-free formulation of SC IFNβ-1a 44µg tiw was more efficacious than placebo in preventing the development of brain lesions in the 16-week IMPROVE trial. In the 96-week REGARD trial, the efficacy of SC IFNβ-1a 44 µg tiw was not significantly different to that of glatiramer acetate for clinical endpoints, although it was associated with reduced development of brain lesions compared with glatiramer acetate, according to some MRI end-points.

In the 36-month CAMMS223 trial, alemtuzumab led to significantly lower relapse rates and risk of developing sustained disability than SC IFNβ-1a 44 µg tiw, and was generally more efficacious according to other clinical and MRI endpoints.

Across trials, influenza-like symptoms, injection-site reactions, haematological disturbances and hepatic enzyme abnormalities were the most common treatment-emergent adverse events occurring with SC IFNβ-1a. In the PRISMS trial, SC IFNβ-1a 22 and 44µg tiw recipients had more injection-site reactions than placebo recipients and, at the higher dosage, haematological disturbances and increases in ALT levels were also significantly more frequent than with placebo. Pooled data from clinical trials and postmarketing surveillance indicate that haematological and hepatic adverse events are generally asymptomatic and rarely result in treatment discontinuation. Nevertheless, some cases of serious hepatic complications have been reported.

In cost-utility studies, first-line therapies for RRMS, including SC IFNβ-1a, all exceeded commonly accepted US thresholds for incremental cost per quality-adjusted life-years gained relative to symptomatic treatment. However, because of patient need and the difficulty in adequately assessing cost utility in a gradually progressive disease, these agents have been made available to many patients worldwide through special access programmes.

Overall, SC IFNβ-1a has a favourable risk-benefit ratio and is a valuable first-line treatment option for patients with relapsing MS.

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Sanford, M., Lyseng-Williamson, K.A. Subcutaneous Recombinant Interferon-β-1a (Rebif®). Drugs 71, 1865–1891 (2011). https://doi.org/10.2165/11207540-000000000-00000

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