The 5-year Tysabri global observational program in safety (TYGRIS) study confirms the long-term safety profile of natalizumab treatment in multiple sclerosis.

BACKGROUND: Natalizumab is an effective treatment for multiple sclerosis (MS) and has a well-characterized safety profile, with more than 10 years of postmarketing experience. TYGRIS was a 5-year observational cohort study designed to obtain long-term safety data in natalizumab-treated MS patients. We examined the incidence and pattern of serious adverse events (SAEs) in this large postmarketing sample of natalizumab-treated patients. METHODS: Investigators reported SAEs in natalizumab-treated patients. Malignancy incidence rates were compared with rates in the general population using external databases. RESULTS: Of 6508 enrolled patients, 4938 (75.9%) completed the study. SAEs occurring in more than 0.5% of patients included urinary tract infection (n = 50; 0.8%), pneumonia (n = 46; 0.7%), progressive multifocal leukoencephalopathy (PML; n = 44; 0.7%), and immune reconstitution inflammatory syndrome (n = 44; 0.7%). Fifty-five patients (0.9%) experienced treatment-emergent serious opportunistic infections, 44 of which were PML. Two patients with PML died. The overall malignancy incidence rate was 449.0 per 100,000 patient-years (95% confidence interval [CI], 375.1-533.1). With few exceptions, incidence rates for individual malignancies had 95% CIs encompassing incidence rates in the general population. Hepatotoxic events occurred in 6 patients; 4 patients had evidence of alternative cause or confounders. Of 96 fatal events, investigators considered 81 unrelated or unlikely to be related to treatment and 5 related or possibly related; causality was not provided for 10. CONCLUSION: Data from this large, long-term study indicate that the nature, character, and frequency of SAEs in real-world settings are consistent with natalizumab's known safety profile. (Funded by Biogen; ClinicalTrials.gov identifiers: NCT00477113 and NCT00483847.).