PMID- 27645341 OWN - NLM STAT- MEDLINE DCOM- 20170228 LR - 20220408 IS - 2211-0356 (Electronic) IS - 2211-0348 (Linking) VI - 9 DP - 2016 Sep TI - Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies. PG - 36-46 LID - S2211-0348(16)30062-1 [pii] LID - 10.1016/j.msard.2016.05.010 [doi] AB - BACKGROUND: Daclizumab has been evaluated in multicentre, randomised, double-blind studies for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). Safety and tolerability are key considerations in MS treatment selection, as they influence adherence to medication. OBJECTIVE: Evaluate the safety of daclizumab in patients with RRMS from an integrated analysis of six clinical studies. METHODS: Patients treated with at least one dose of subcutaneous daclizumab 150mg or 300mg monthly in three completed and three ongoing clinical studies were included in this integrated analysis. Cumulative incidence of treatment-emergent adverse events (AEs) was the primary endpoint. RESULTS: This analysis included 2236 patients with 5214 patient-years of exposure to daclizumab. The cumulative incidence of any AE was 84% and of any serious AE excluding MS relapse was 16%. The incidences of AEs when evaluated by 6-month intervals remained stable over the 6.5 years of maximum follow-up. Most AEs were mild or moderate in severity. An important safety concern associated with daclizumab therapy involved hepatic AEs (16%) and serum transaminase elevations at least three times the upper limit of normal (10%), most of which were asymptomatic, self-limiting, and non-recurring. Cumulative incidences of cutaneous, infectious, and gastrointestinal AEs were 33%, 59%, and 25%, respectively; most events either resolved spontaneously or were treated successfully with standard medical interventions and did not result in discontinuation of treatment. CONCLUSION: This integrated analysis demonstrates that treatment of RRMS with daclizumab for periods of up to 6.5 years is associated with an acceptable safety profile with no evidence of cumulative toxicity over time. CI - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Giovannoni, Gavin AU - Giovannoni G AD - Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, UK. Electronic address: g.giovannoni@qmul.ac.uk. FAU - Kappos, Ludwig AU - Kappos L AD - Neurology, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Electronic address: ludwig.kappos@usb.ch. FAU - Gold, Ralf AU - Gold R AD - Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. Electronic address: Ralf.Gold@ruhr-uni-bochum.de. FAU - Khatri, Bhupendra O AU - Khatri BO AD - Center for Neurological Disorders and The Regional Multiple Sclerosis Center, Wheaton Franciscan Health Care St. Francis Hospital, 3237S 16th Street, Milwaukee, WI 53215, USA. Electronic address: bokhatri@aol.com. FAU - Selmaj, Krzysztof AU - Selmaj K AD - Department of Neurology, Medical University of Lodz, ul. Kopcinskiego 22, 90-153 Lodz, Poland. Electronic address: kselmaj@afazja.am.lodz.pl. FAU - Umans, Kimberly AU - Umans K AD - Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: kim.umans@biogen.com. FAU - Greenberg, Steven J AU - Greenberg SJ AD - AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA. Electronic address: steven.greenberg@abbvie.com. FAU - Sweetser, Marianne AU - Sweetser M AD - Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: msweetser@alnylam.com. FAU - Elkins, Jacob AU - Elkins J AD - Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: jake.elkins@biogen.com. FAU - McCroskery, Peter AU - McCroskery P AD - Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: peter.mccroskery@biogen.com. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20160511 PL - Netherlands TA - Mult Scler Relat Disord JT - Multiple sclerosis and related disorders JID - 101580247 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Immunoglobulin G) RN - 0 (Immunosuppressive Agents) RN - CUJ2MVI71Y (Daclizumab) SB - IM MH - Adult MH - Antibodies, Monoclonal, Humanized/*adverse effects/*therapeutic use MH - Daclizumab MH - Disability Evaluation MH - Female MH - Follow-Up Studies MH - Humans MH - Immunoglobulin G/*adverse effects/*therapeutic use MH - Immunosuppressive Agents/*adverse effects/*therapeutic use MH - Male MH - Multiple Sclerosis, Relapsing-Remitting/*drug therapy/epidemiology/physiopathology MH - Treatment Outcome OTO - NOTNLM OT - Clinical study OT - Daclizumab OT - Relapsing-remitting multiple sclerosis OT - Safety OT - Tolerability EDAT- 2016/09/21 06:00 MHDA- 2017/03/01 06:00 CRDT- 2016/09/21 06:00 PHST- 2015/12/22 00:00 [received] PHST- 2016/04/21 00:00 [revised] PHST- 2016/05/10 00:00 [accepted] PHST- 2016/09/21 06:00 [entrez] PHST- 2016/09/21 06:00 [pubmed] PHST- 2017/03/01 06:00 [medline] AID - S2211-0348(16)30062-1 [pii] AID - 10.1016/j.msard.2016.05.010 [doi] PST - ppublish SO - Mult Scler Relat Disord. 2016 Sep;9:36-46. doi: 10.1016/j.msard.2016.05.010. Epub 2016 May 11.