Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label extension study

Ralf Gold, Ernst Wilhelm Radue, Gavin Giovannoni, Krzysztof Selmaj, Eva Havrdova, Dusan Stefoski, Till Sprenger, Xavier Montalban, Stanley Cohan, Kimberly Umans, Steven J. Greenberg, Gulden Ozen, Jacob Elkins

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42 Scopus citations

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. Trial registration: Clinicaltrials.gov NCT01051349 ; first registered January 15, 2010.

Original languageEnglish
Article number117
JournalBMC Neurology
Volume16
Issue number1
DOIs
StatePublished - 26 Jul 2016
Externally publishedYes

Keywords

  • Daclizumab
  • Efficacy
  • Relapsing-remitting multiple sclerosis
  • Safety

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