A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis.
A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to briakinumab (200 mg at weeks 0 and 4 and 100 mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 (P<0.001 each). At week 52, 79.2% of q4-wk-treated patients achieved PGA "clear/minimal" compared with 41.6% and 6.0% of q12-wk and placebo-treated patients, respectively (P<0.001 for all treatment comparisons). Higher numbers of the following adverse events (AEs) of interest were observed with briakinumab during the placebo-controlled period, suggesting the need for surveillance for these events: serious infections (five vs. one event with briakinumab vs. placebo, respectively), nonmelanoma skin cancers (NMSCs; four vs. zero squamous cell carcinomas (SCCs)), and major adverse cardiovascular events (MACEs; five vs. zero events).
Division of Dermatology, NorthShore University HealthSystem and University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60077, USA. kgordon@northshore.org
Kenneth B
KB
Gordon
Richard G
RG
Langley
Alice B
AB
Gottlieb
Kim A
KA
Papp
Gerald G
GG
Krueger
Bruce E
BE
Strober
David A
DA
Williams
Yihua
Y
Gu
Joaquin M
JM
Valdes
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors*; D053759:Interleukin-23 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D018664:Interleukin-12; C544528:briakinumab