BACKGROUND:Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. OBJECTIVES: To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. METHODS: A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). RESULTS: At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. CONCLUSIONS:Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.
RCT Entities:
BACKGROUND:Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. OBJECTIVES: To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. METHODS: A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). RESULTS: At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. CONCLUSIONS:Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.
Authors: Andrew Blauvelt; Marc Brown; Kenneth B Gordon; Arthur Kavanaugh; Craig T Leonardi; Eggert Stockfleth; Bruce Strober; Neil A Swanson; George Martin Journal: J Clin Aesthet Dermatol Date: 2013-09
Authors: Michele W L Teng; Edward P Bowman; Joshua J McElwee; Mark J Smyth; Jean-Laurent Casanova; Andrea M Cooper; Daniel J Cua Journal: Nat Med Date: 2015-06-29 Impact factor: 53.440
Authors: Roger R Beerli; Monika Bauer; Andrea Fritzer; Lindsey B Rosen; Regula B Buser; Markus Hanner; Melanie Maudrich; Mario Nebenfuehr; Jorge Alejandro Sepulveda Toepfer; Susanne Mangold; Anton Bauer; Steven M Holland; Sarah K Browne; Andreas Meinke Journal: MAbs Date: 2014 Impact factor: 5.857