Long-term safety and efficacy of daclizumab beta in relapsing–remitting multiple sclerosis: 6-year results from the SELECTED open-label extension study

• Published in: Journal of neurology Vol. 267; no. 10; pp. 2851 - 2864
• Main Authors: Gold, Ralf, Radue, Ernst-Wilhelm, Giovannoni, Gavin, Selmaj, Krzysztof, Havrdova, Eva Kubala, Montalban, Xavier, Stefoski, Dusan, Sprenger, Till, Robinson, Randy R., Fam, Sami, Smith, Jonathan, Chalkias, Spyros, Giannattasio, Giorgio, Lima, Gabriel, Castro-Borrero, Wanda
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2020; Springer Nature B.V
• Subjects: Adult; Adverse events; Antibodies, Monoclonal, Humanized; Daclizumab - adverse effects; Daclizumab - therapeutic use; Encephalitis; Female; Humans; Immunoglobulin G; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Liver; Male; Medicine; Medicine & Public Health; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Neurology; Neuroradiology; Neurosciences; Original Communication; Safety; SELECTED; Clinical trial; Daclizumab beta; Relapsing–remitting multiple sclerosis
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-020-09835-y

Objective
SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED.
Methods
Eligible participants who completed 1–2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION.
Results
Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0–24 was 0.21 (0.16–0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time.
Conclusions
The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED.
Trial registration
Clinicaltrials.gov NCT01051349; first registered on January 15, 2010.