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.).

Informations de copyright

Copyright © 2019. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest JF has received personal compensation for consulting, speaking, and scientific advisory boards from Biogen, Genzyme, and Teva and financial support for research activities from Biogen, Genentech-Roche, Genzyme, and Teva. CC-I was an employee of and holder of stock and/or stock options in Biogen at the time of this analysis and is now an employee of Alexion Pharmaceuticals, which was not in any way associated with this study. JS was a contractor for Biogen at the time of this analysis and is now an employee of and may hold stock and/or stock options in Biogen. KE, P-RH, and KS are employees of and may hold stock and/or stock options in Biogen. LL and RK were employees of Biogen at the time of these analyses and may hold stock in Biogen. MS has received honoraria for scientific lectures or consultancy from Alexion, Bayer Healthcare, Biogen, CSL Behring, Grifols, MedDay, Merck Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva. His institution received research support from Biogen, Sanofi Genzyme, and Merck Serono. PV has received honoraria and consulting fees from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi Genzyme, Servier, and Teva and research support from Biogen, Merck Serono, Novartis, and Sanofi Genzyme. MH has served on a medical advisory board for Biogen and the editorial board of the Multiple Sclerosis Journal and has received speaker honoraria from Bayer-Schering, Biogen, and Novartis and research support from Dystonia Ireland, the European Dystonia Foundation, and the Health Research Board of Ireland. FM has no relevant conflicts of interest to disclose.