Natalizumab versus fingolimod and dimethyl fumarate in multiple sclerosis treatment

Objective To compare 2‐year effectiveness and discontinuation of natalizumab ( NTZ ) versus fingolimod ( FTY ) and dimethyl fumarate ( DMF ) in the treatment of multiple sclerosis ( MS ). Methods Patients prescribed NTZ , FTY , or DMF at the Rocky Mountain MS Center at University of Colorado were identified. Clinician‐reported data were retrospectively collected. Outcomes include a composite effectiveness measure consisting of new T2 lesion, gadolinium‐enhancing lesion, and/or clinical relapse, individual effectiveness outcomes and discontinuation over 2 years. Logistic regression was used for data analysis on patients matched by propensity scores and using ATT doubly robust weighting estimator. Results A total of 451, 271, and 342 patients were evaluated on NTZ , FTY , and DMF over 2 years, respectively. Patients had a mean age of 39.8 ( NTZ ), 42.5( FTY ), and 45.8 ( DMF ) years; were predominantly female (76.7% NTZ ; 72.0% FTY ; 69.6% DMF ); and had a mean MS disease duration of 11–12 years for all groups. At ≤24 months, 22.2%, 34.7%, and 33.6% experienced a new T2 lesion, gadolinium‐enhancing lesion, and/or clinical relapse on NTZ , FTY , and DMF , respectively. Using ATT doubly robust weighting estimator, FTY versus NTZ and DMF versus NTZ had an odds ratio of 2.00 (95% CI :[1.41–2.85], P  < 0.001) and 2.38 [95% CI : 1.68–3.37], P  < 0.001) respectively, for experiencing a new T2 lesion, gadolinium enhancing lesion, and/or clinical relapse. At ≤24 months, 32.6%, 34.3%, and 47.1% discontinued NTZ , FTY , and DMF , respectively. The majority of discontinuations were due to becoming JCV positive(12.6%) for NTZ and due to adverse events for both FTY (17%) and DMF (24.0%). Interpretation NTZ appears to be more effective and tolerable than FTY and DMF .