Abstract and Introduction
Abstract
Objective To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS).
Methods In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg or placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years.
Results Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms.
Conclusions These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS.
Introduction
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that can lead to the accumulation of significant disability. As the disease typically lasts for several decades, long-term follow-up studies are important to better understand the impact of disease-modifying therapies (DMTs). However, conducting these trials can be challenging due to many methodological barriers, including the difficulties associated with patient ascertainment.
Clinical trials have shown that the early initiation of treatment with interferon beta-1b (IFNB1b; Betaferon/Betaseron; Bayer HealthCare Pharmaceuticals) can improve outcomes for patients with MS. The BENEFIT (BEtaferon/BEtaseron in Newly Emerging MS For Initial Treatment) study examined the impact of IFNB1b in patients with a clinically isolated syndrome (CIS). In this trial, early IFNB1b treatment reduced the number of patients progressing to clinically definite MS (CDMS) compared with placebo after 3 years (37% vs 51%, hazard ratios (HR) 0.59) and 5 years (46% vs 57%, HR 0.63). Annualised relapse rate (ARR) and Paced Auditory Serial Addition Task (PASAT) scores were also in favour of the early treatment arm.
We report results of an 8-year, non-interventional extension of BENEFIT focusing on the description of the course of disease in the overall study population and on the comparison of outcomes in the early versus delayed treatment arms.