TY - JOUR
T1 - Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis:
T2 - 3-year results from the SELECTED open-label extension study
AU - Gold, Ralf
AU - Radue, Ernst-Wilhelm
AU - Giovannoni, Gavin
AU - Selmaj, Krzysztof
AU - Havrdova, Eva
AU - Stefoski, Dusan
AU - Sprenger, Till
AU - Montalban, Xavier
AU - Cohan, Stanley
AU - Umans, Kimberly
AU - Greenberg, Steven J.
AU - Ozen, Gulden
AU - Elkins, Jacob
PY - 2016/7/26
Y1 - 2016/7/26
N2 - 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 was1.26 (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.
AB - 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 was1.26 (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.
KW - Daclizumab
KW - Efficacy
KW - Relapsing-remitting multiple sclerosis
KW - Safety
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=uab_pure&SrcAuth=WosAPI&KeyUT=WOS:000380289700004&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1186/s12883-016-0635-y
DO - 10.1186/s12883-016-0635-y
M3 - Article
C2 - 27461166
SN - 1471-2377
VL - 16
JO - BMC Neurology
JF - BMC Neurology
M1 - 117
ER -