title: Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label extension study.
abstract: BACKGROUND
  Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study.
  
  
  METHODS
  An interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study.
  
  
  RESULTS
  The SELECTED study enrolled 90% of patients who completed SELECTION. In the safety and efficacy analysis (N = 410), median treatment time in SELECTED was 25 months (range, <1-45). Adverse events (AEs) were reported in 76% of patients, serious AEs (SAEs) excluding MS relapse in 16%, and treatment discontinuation due to AEs including multiple sclerosis (MS) relapse in 12%. AEs were primarily of mild to moderate severity, and common AEs (≥10%), excluding MS relapse, were nasopharyngitis (12%) and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients), excluding MS relapses, were increased serum hepatic enzymes, pneumonia, ulcerative colitis, and urinary tract infection (<1% each). Incidences of AE groups of interest include cutaneous events (28%), cutaneous SAEs (2%), gastrointestinal SAEs (2%), hepatic SAEs, (1%) and malignancies (1%). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time and no deaths were reported. The adjusted annualized relapse rate (95% confidence interval (CI)) analyzed at 6-month intervals was 0.15 (0.10-0.22) for weeks 97-120 and 0.15 (0.10-0.21) for weeks 121-144. In year 3, the adjusted mean (95% CI) number of new/newly enlarging T2 hyperintense lesions was 1.26 (0.93-1.72) and the mean (median) annualized change in brain volume was -0.32% (-0.34%).
  
  
  CONCLUSIONS
  The AE incidence did not increase with extension of therapy into year 3 in SELECTED; the safety profile was similar to that previously observed. The clinical efficacy of daclizumab was sustained over the 3 years comprising the SELECT TRILOGY, although potential selection bias cannot be excluded.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01051349; first registered January 15, 2010.
authors.affiliation: Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany. ralf.gold@rub.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland.
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.affiliation: Queen Mary University of London, Blizard Institute, London School of Medicine and Dentistry, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Rush University Medical Center, Chicago, IL, USA.
authors.forename: Dusan
authors.initials: D
authors.lastname: Stefoski
authors.affiliation: Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland.|DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Sprenger
authors.affiliation: Hospital Vall d'Hebron University, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: Providence Multiple Sclerosis Center, Portland, OR, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cohan
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Umans
authors.affiliation: AbbVie Biotherapeutics Inc., Redwood, CA, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Greenberg
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Gulden
authors.initials: G
authors.lastname: Ozen
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Elkins
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000187:drug effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000139:chemically induced; D000077561:Daclizumab; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D057194:Intention to Treat Analysis; D053645:Interleukin-2 Receptor alpha Subunit / Q000008:administration & dosage / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D009304:Nasopharyngitis / Q000139:chemically induced; D011014:Pneumonia / Q000139:chemically induced; D012008:Recurrence; D012141:Respiratory Tract Infections / Q000139:chemically induced; D012449:Safety; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D000077561:Daclizumab; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Daclizumab; Efficacy; Relapsing-remitting multiple sclerosis; Safety