What to expect after natalizumab cessation in a real-life setting

Background: To minimize the risk of progressive multifocal leucoencephalopathy (PML), treatment with natalizumab is often stopped after 2 years, but evidence upon rebound of disease activity is limited and controversial.

Objective: To evaluate effects of natalizumab discontinuation on clinical disease activity within twelve months after cessation.

Methods: We retrospectively analyzed data of 201 patients with MS who discontinued natalizumab between 2007 and 2012. Mean change scores of annualized relapse rate (ARR) and expanded disability status scale (EDSS) were calculated for detection of rebound disease activity after twelve months.

Results: Natalizumab exposure did not exceed 2 years in 50.2% of patients, and the most common reasons for discontinuation were a long treatment period and concern of PML (56%). A total of 11.9% experienced a rebound phenomenon within twelve months. Mean ARR prenatalizumab was lower (P = 0.001, 95% CI -1.0-0.000) and treatment response to natalizumab poorer (P < 0.001, 95% CI 0.4-1.3) in patients with rebound compared to those without, but rebound was not associated with brief exposure to natalizumab (P = 0.159, 95% CI -9.3-1.5). 86.1% of patients switched to another therapy. Patients without rebound were found more often in the group starting an alternative treatment early (P = 0.013).

Conclusion: Our data suggest that rebound of MS disease activity affects a subgroup of patients (11.9%), especially those with low disease activity before natalizumab therapy and a longer treatment gap after its withdrawal.