Tolerability Results from Year 1 of the PRISMS-2 Two-Year Randomized Controlled Trial of IFN ß-1a SC tiw Compared with Placebo

Background: In the PRISMS-2 study, interferon beta-1a (IFN β-1a) 44 and 22 µg subcutaneously (SC) three times weekly (tiw) demonstrated significant efficacy compared with placebo in patients with relapsing–remitting multiple sclerosis. Tolerability results indicated that flu-like symptoms (FLS) were common in all groups, and injection-site reactions (ISRs) during the first 3 months of therapy were common for IFN β-1a SC with no apparent difference between doses.¹

Objectives: To evaluate tolerability data over 1 year from PRISMS-2 at incremental time periods and by severity, in order to further characterize the safety profile of IFN β-1a SC tiw.

Methods: In the PRISMS-2 study, 560 patients with ≥2 relapses over 2 years and Expanded Disability Status Scale score of 0–5.0 were randomly assigned to IFN β-1a 44 or 22 µg SC tiw or placebo for 2 years. These post hoc analyses evaluated the frequency and severity of adverse events (AEs; eg, ISRs and FLS) at incremental time periods over 1 year (0–3, 3–6, and 6–12 months) and the rate of AEs leading to discontinuation. 

Results: Over 12 months, treatment-emergent AEs leading to discontinuation were rare and exceeded 1% incidence only for ISRs in the IFN β-1a 44 µg SC tiw group. More patients receiving IFN β-1a 44 or 22 µg SC vs placebo experienced ISRs over 12 months; no significant differences were observed for FLS. ISRs predominantly occurred over 0–3 months for IFN β-1a 44 (31.5% [58/184]) or 22 (30.2% [57/189]) µg SC vs placebo (5.9% [11/187]) and decreased thereafter from 3–6 months (IFN β-1a 44 [3.8%] or 22 [1.6%] µg SC vs placebo [1.1%]) and 6–12 months (IFN β-1a 44 [3.8%] or 22 [1.1%] µg SC vs placebo [0.5%]). FLS also predominantly occurred over 0–3 months (IFN β-1a 44 [29.3%] or 22 [23.8%] µg SC vs placebo [18.7%]) and decreased from 3–6 months (IFN β-1a 44 [8.7%] or 22 [4.8%] µg SC vs placebo [6.4%]) and 6–12 months (IFN β-1a 44 [9.2%] or 22 [7.9%] µg SC vs placebo [8.0%]). These AEs were predominately mild or moderate: over 12 months, 1.6% of IFN β-1a 22 µg SC patients had severe FLS, and 1.6% and 1.1% of IFN β-1a 44 and 22 µg SC patients, respectively, had severe ISRs.  

Conclusions: There was a steep decline in the incidence of AEs after the first 3 months of IFN β-1a SC tiw therapy. Over 1 year, most ISRs and FLS were mild. 

¹PRISMS Study Group. Lancet 1998;352:1498–504.