Citation

Kappos L, Cohan S, Arnold DL, Robinson RR, Holman J, Fam S, Parks B, Xiao S, Castro-Borrero W. Ther. Adv. Neurol. Disorders 2021; 14.

Copyright

(Copyright © 2021)

DOI

10.1177/1756286420987941

PMID

unavailable

Abstract

BACKGROUND: EXTEND (NCT01797965), an open-label extension study, evaluated the safety and efficacy of daclizumab beta in participants with relapsing multiple sclerosis (MS) who had completed the randomized DECIDE study.

METHODS: Eligible participants who received either daclizumab beta or interferon beta-1a in DECIDE received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 5 years in EXTEND, followed by 24 weeks of post-dosing follow-up. Safety and tolerability were evaluated, as were clinical efficacy and magnetic resonance imaging (MRI). EXTEND was terminated ahead of schedule by the sponsors.

RESULTS: The total safety population (N = 1203) received at least one dose of daclizumab beta in EXTEND. In the DECIDE and EXTEND combined periods, the median number of doses of daclizumab beta was 53; median time on treatment was 196 weeks. By 24 September 2018, the end of the study, 110/1203 (9%) participants had completed the protocol-specified treatment period and 1101/1203 (92%) had experienced an adverse event (AE). The most commonly reported AEs were MS relapse, nasopharyngitis, and upper respiratory tract infection. Hepatic events (18%), cutaneous events (45%), and infections (62%) were common treatment-related AEs. The incidence of serious AEs was 29%, most commonly MS relapse and infections. The incidence of immune-mediated disorders was 2%; three of seven were encephalitis. Two of six deaths were considered treatment related. In participants who received continuous daclizumab beta throughout DECIDE and EXTEND, the treatment effects on clinical and MRI outcomes were maintained for up to 6 years.

CONCLUSION: Results from the combined DECIDE-EXTEND study elucidate outcomes of longer-term treatment with daclizumab beta in the clinical trial setting and underscore the importance of pharmacovigilance with immunomodulatory therapies in the real-world setting. © The Author(s), 2021.

Language: en

Keywords

adult; human; female; male; depression; randomized controlled trial; suicide attempt; epilepsy; pancreatitis; controlled study; human tissue; autoimmune disease; thrombocytopenia; nuclear magnetic resonance imaging; breast cancer; inguinal hernia; drug safety; rheumatoid arthritis; follow up; drug efficacy; drug tolerability; agranulocytosis; drug withdrawal; fever; erythema; lymphocytopenia; rash; neurologic disease; relapse; psoriasis; alanine aminotransferase; aspartate aminotransferase; gastrointestinal disease; encephalitis; autoimmunity; hepatitis E; multiple sclerosis; hemolytic anemia; angioneurotic edema; pneumonia; liver necrosis; acute pancreatitis; cytomegalovirus infection; urinary tract infection; toxic hepatitis; gamma glutamyltransferase; Article; beta1a interferon; colitis; jaundice; bilirubin; eczema; septic shock; upper respiratory tract infection; uterus myoma; uveitis; respiratory tract infection; cholecystitis; lymphadenopathy; appendicitis; liver function test; sarcoidosis; maculopapular rash; Guillain Barre syndrome; cholelithiasis; rhinopharyngitis; daclizumab; gadolinium; celiac disease; seborrheic dermatitis; vitiligo; faintness; alkaline phosphatase; hyperplasia; hypertransaminasemia; clinical outcome; mortality rate; lymphadenitis; adverse event; pemphigoid; autoimmune hemolytic anemia; lung sarcoidosis; lymph node biopsy