Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes

TLDR

The study evaluated the efficacy, safety, and tolerability of every‑other‑day interferon beta‑1b in patients with a first clinical event suggestive of multiple sclerosis. A multicenter, randomized, double‑blind, placebo‑controlled trial enrolled patients with a first demyelinating event and at least two silent brain MRI lesions, assigning them to IFNB‑1b 250 µg SC every other day or placebo until CDMS diagnosis or 24 months of follow‑up. After two years, 45 % of placebo patients progressed to clinically definite MS versus 85 % meeting McDonald criteria, while IFNB‑1b delayed CDMS and McDonald MS (hazard ratios 0.50 and 0.54, p < 0.0001 and p < 0.00001) with a low dropout rate, supporting its therapeutic use.

Abstract

<b>Objective: </b> To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome). <b>Methods: </b> We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 μg subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months. <b>Results: </b> After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (<i>p</i> &lt; 0.0001) and McDonald MS (<i>p</i> &lt; 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group). <b>Conclusions: </b> Interferon beta-1b 250 μg subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis.