title: Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: 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.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Gudrunstraße 56, 44791 Bochum, Germany. Electronic address: Ralf.Gold@ruhr-uni-bochum.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: 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.
authors.forename: Bhupendra O
authors.initials: BO
authors.lastname: Khatri
authors.affiliation: Department of Neurology, Medical University of Lodz, ul. Kopcinskiego 22, 90-153 Lodz, Poland. Electronic address: kselmaj@afazja.am.lodz.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: kim.umans@biogen.com.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Umans
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA. Electronic address: steven.greenberg@abbvie.com.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Greenberg
authors.affiliation: Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: msweetser@alnylam.com.
authors.forename: Marianne
authors.initials: M
authors.lastname: Sweetser
authors.affiliation: Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: jake.elkins@biogen.com.
authors.forename: Jacob
authors.initials: J
authors.lastname: Elkins
authors.affiliation: Biogen, 225 Binney Street, Cambridge, MA 02142, USA. Electronic address: peter.mccroskery@biogen.com.
authors.forename: Peter
authors.initials: P
authors.lastname: McCroskery
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D000077561:Daclizumab; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab
keywords: Clinical study; Daclizumab; Relapsing-remitting multiple sclerosis; Safety; Tolerability