BackgroundDaclizumab 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.MethodsAn interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study.ResultsThe 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 %).ConclusionsThe 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 registrationClinicaltrials.gov NCT01051349; first registered January 15, 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0635-y) contains supplementary material, which is available to authorized users.

Background: For patients with relapsing-remitting multiple sclerosis (RRMS) undergoing continuous immunomodulatory therapy, understanding whether vaccinations can be performed safely and effectively is important. We tested the immune response to inactivated seasonal influenza vaccine during long-term daclizumab beta treatment.

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BackgroundIn SELECTION, an extension study of SELECT evaluating the efficacy/safety of daclizumab high-yield process (DAC HYP) versus placebo, efficacy of DAC HYP in reducing clinical/radiological disease activity in relapsing-remitting multiple sclerosis (RRMS) patients demonstrated in SELECT was confirmed over 1–2 years.MethodsSELECTED is an ongoing, 6-year, single-arm, open-label study evaluating the efficacy/safety of 150 mg subcutaneous DAC HYP every 4 weeks in patients who completed SELECTION. An interim analysis was performed in January 2014, for patients with ≥3 years' continuous DAC HYP treatment.ResultsOverall, 410 (90%) patients from SELECTION enrolled in SELECTED and 94 had been continuously treated at the time of the data-cut. Adjusted annualized relapse rate was 0.089 (95% confidence interval [CI]: 0.033–0.244) for weeks 96–120 and 0.047 (95% CI: 0.012–0.187) for weeks 120–144. In year 3, the adjusted mean number of new/newly enlarging T2 hyperintense lesions was 0.56 (95% CI: 0.24–1.32). Brain atrophy rate was reduced in year 3 from years 1–2 (mean annualized change: −0.3%). The safety profile in year 3 was similar to that observed in years 1–2.ConclusionsEfficacy of DAC HYP was sustained over 3 years in RRMS patients, supporting long-term maintenance therapy with DAC HYP.Sponsors: Biogen, AbbVie Biotherapeutics.