Standard Dose Weekly Intramuscular Beta Interferon-1a May Be Inadequate for Some Patients with Multiple Sclerosis: A 19-Year Clinical Experience Using Twice a Week Dosage

INTRODUCTION: Results from several clinical trials suggest there is a dose–response effect for beta interferon-1a (INFβ1a) in multiple sclerosis (MS). METHODS: Our objective was to confirm these results through a retrospective analysis of patients with MS who had breakthrough disease (BD) on intramuscular (IM) INFβ1a (Avonex®) once per week (QW), who were switched to twice per week (BIW) IM INFβ1a between 1995 and 2015. The primary outcome measure was no further BD for at least 24 months. A secondary outcome measure was decrease in mean percentage of disease activity over time. BD was defined as continued relapses, new T2 or enhanced lesions on magnetic resonance imaging (MRI) of the brain, or worsening of the Expanded Disability Status Scale (EDSS) or the neurological examination. RESULTS: Among 92 patients on QW IM INFβ1a, 53 patients with BD were switched to BIW IM INFβ1a. Of these 53 patients, 44 had adequate follow-up for at least 2 years. Twenty-three of these had no further BD for 24 months or more (range 24–192 months). Beta interferon neutralizing antibody testing was negative in 19 patients. An intent-to-treat analysis of the uncensored data from 52 switched patients also supported a treatment benefit. CONCLUSION: For patients with MS having breakthrough disease on QW INFβ1a, switching to more frequently administered INFβ may be an option. Advantages to using IM INFβ1a for this include no skin reactions and a lower incidence of neutralizing antibodies. Further pragmatic, observational, larger-group studies comparing treatment with Avonex® and higher dosed IM INFβ1a, such as the recently FDA-approved IM peginterferon beta-1a, may be indicated.