Duration of natalizumab therapy and reasons for discontinuation in a multiple sclerosis population

Objective: To determine multiple sclerosis patient characteristics that predict a shorter duration of natalizumab treatment.

Methods: The Tysabri Outreach: Unified Commitment to Health database was reviewed to identify patients treated with natalizumab at our centers. Cox proportional hazards models were used to evaluate patient characteristics associated with shorter treatment durations on natalizumab. Associations were also assessed with respect to specific reasons for stopping natalizumab.

Results: We identified 554 patients who began and stopped natalizumab treatment during the observation period. The average disease duration at natalizumab initiation was 7.6 years, and the average number of infusions was 30. The multivariable Cox proportional hazards model identified greater age (P = 0.035), longer disease duration (P < 0.001), progressive relapsing multiple sclerosis phenotype (P = 0.003), current smoking (P = 0.031), and greater depression (P = 0.026) as significant predictors for natalizumab discontinuation. Greater disability levels (P = 0.022) and gadolinium-enhancing lesions on baseline magnetic resonance imaging (P < 0.001) were significantly associated with longer natalizumab treatment. Individuals with progressive relapsing multiple sclerosis had a 14-fold increased hazard of discontinuing natalizumab due to inflammatory events (P < 0.001) than those with relapsing-remitting multiple sclerosis. Smokers had an 80% increased hazard of discontinuation due to intolerance (P = 0.008).

Conclusions: Our results suggest that smoking, depression, and a progressive relapsing multiple sclerosis phenotype are associated with shorter natalizumab treatment durations.