Is natalizumab overshooting its rebound?

Abstract

After over a decade of multiple sclerosis (MS) therapies with only modest efficacy and inconvenient administration, the monoclonal antibody natalizumab was a welcomed addition to the MS treatment armamentarium. Natalizumab's efficacy included a 67% reduction in clinical relapses, a 42% reduction in disability progression, and a 92% reduction in gadolinium-enhancing lesions over 2 years, all compared to placebo.1 The euphoria surrounding this VLA-4 adhesion molecule antagonist was dampened when progressive multifocal leukoencephalopathy was identified as a rare, late complication of natalizumab treatment, with an estimated incidence of 1:1,000 over 18 months of therapy. In this issue of Neurology ®, Vellinga et al.2 present additional data on natalizumab which suggest that patients with MS may have rebound in MRI activity, although not clinical relapses, after discontinuation of natalizumab. The authors evaluated 21 patients enrolled in the natalizumab phase III clinical trials in their center. They compared new T2 lesions on brain MRI over a 7- to 54-month period prior to treatment with natalizumab, and compared that to a 15-month period after treatment discontinuation. They found that lesion activity increased threefold between the two periods, and this increase was almost entirely driven by patients who received only one to eight infusions (median two). Patients who received 30 to 37 infusions had very similar MRI activity before and after treatment. These findings are intriguing, although significant limitations include …