Clinical outcomes in patients with relapsing-remitting multiple sclerosis who switch from natalizumab to delayed-release dimethyl fumarate: A multicenter retrospective observational study (STRATEGY)

Abstract Background Delayed-release dimethyl fumarate (DMF) may be a therapeutic option for patients with relapsing-remitting multiple sclerosis (RRMS) who are treated with natalizumab and require a change in therapy. However, there is limited information regarding predictors of favorable treatment outcomes in patients switching from natalizumab to DMF. Clinical practices and sequencing protocols vary. Herein, we present the clinical results, including annualized relapse rate (ARR) and risk of relapse, of a phase 4 retrospective observational study of patients with RRMS who switched from natalizumab to DMF in a community practice setting (STRATEGY). Methods STRATEGY was performed through a single time point medical record abstraction; no study visits or procedures were required. Key inclusion criteria included age ≥18 years, RRMS diagnosis (McDonald criteria, 2010 revised), ≥12 months of continuous treatment with natalizumab monotherapy before DMF initiation, and initiation of DMF ≥12 months before enrollment. Patients were eligible to enroll regardless of current DMF use. Results A total of 530 patients at 45 US sites enrolled, and 506 met the inclusion criteria and were included in the modified evaluable population for analysis. Mean (SD) age at DMF initiation was 47.0 (10.9) years, with a mean (SD) of 12.7 (7.2) years since MS diagnosis. The mean (SD) duration of natalizumab treatment was 3.4 (1.9) years, and the mean (SD) washout from natalizumab discontinuation to DMF initiation ( n =502) was 101.6 (164.0) days. Overall risk of relapse 12 months after DMF initiation was 19.6%. Overall unadjusted ARR was higher during the 12 months following initiation of DMF treatment compared with the 12 months following initiation of natalizumab treatment (rate ratio, 2.32 [95% CI, 1.69–3.18]; p p p =0.1664). The relapse rate for patients who did not relapse during natalizumab treatment was significantly lower with a washout period of ≤90 days as compared with a washout period of >90 days (rate ratio for relapse rate, 0.49 [95% CI, 0.26–0.90]; p =0.0216). A total of 42 (8%) patients reported ≥1 adverse event leading to DMF discontinuation during the study; the most commonly reported events were gastrointestinal disorders ( n =21; 4%). Conclusions Results from this multicenter retrospective observational study suggest that DMF may be an effective treatment option for patients who discontinue natalizumab in routine clinical practice. ARR was lower in patients who initiated DMF within 90 days of natalizumab discontinuation compared with patients who initiated DMF after 90 days of natalizumab discontinuation. Trial registration ClinicalTrials.gov identifier NCT02159573.