Natalizumab Discontinuation: Observational Study of University of Colorado Patients with Relapsing-Remitting Multiple Sclerosis (P06.170)

Abstract

Objective: Evaluate disease activity among relapsing remitting multiple sclerosis patients during transition off natalizumab therapy. Background Natalizumab (NTZ) is an effective disease modifying drug (DMD) for treatment of relapsing-remitting multiple sclerosis (RRMS)¹. Patients discontinue NTZ for many reasons, including increased risk of progressive multifocal leukoencephalopathy (PML)². Many studies have demonstrated marked increases in gadolinium enhancing (Gd+) lesions and clinical activity among a subset of patients after NTZ withdrawal³. In our retrospective study, we characterized disease activity among patients with RRMS who transitioned off of NTZ. Design/Methods: Seventy-six patients were followed clinically and radiographically over 6 months following NTZ withdrawal. Decision to discontinue NTZ included increased or continued disease activity, adverse events, JCV seropositive status, and the decision to become pregnant. Alternative treatments were initiated after NTZ discontinuation (interferon-β 1a or -β 1b, glatiramer acetate, fingolimod, rituximab, pulsed steroids, or none). Intervals between NTZ discontinuation and start of alternative therapies were documented. Results: Thirty-seven subjects had return of clinical activity (relapse) following NTZ withdrawal. Median time to relapse after NTZ discontinuation was 3 months. Among relapses, the median time between NTZ discontinuation and initiation of an alternative DMD was 0.5 months. Nine severe relapses, defined as disease activity more than 2-fold higher than pre-NTZ were observed (MRI: average pre-NTZ = 0.5 Gd+ lesions; average post-NTZ withdrawal = 7.6 Dd+ lesions). Conclusions: Return of disease activity was noted clinically and radiographically. Disease activity increases within the first 3 months after NTZ discontinuation and is associated with increased time to alternative therapy. More studies are needed to identify patients at risk for increased disease activity in order to develop protocols that minimize disease burden following NTZ discontinuation. We will continue to evaluate the association of disease activity and choice of alternative DMD, duration of NTZ therapy, and interval between discontinuation of NTZ and initiation of alternative therapy. Disclosure: Dr. Nnunukwe has nothing to disclose. Dr. Schreiner has nothing to disclose.