BACKGROUND: Conventional systemic therapies for plaque psoriasis have not fully 
met the needs of patients, and although current biologic treatments are 
generally well tolerated, concerns exist with respect to long-term safety. 
Interleukin (IL)-17A is believed to be an important effector cytokine in the 
pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T 
cells that act outside the established Th1/Th2 paradigm for regulation of innate 
and adaptive immunity.
OBJECTIVES: To assess the efficacy and safety of different doses of secukinumab, 
a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with 
moderate-to-severe plaque psoriasis.
METHODS: Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive 
subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 
25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. 
After the 12-week treatment period, patients entered a follow-up period of 24 
weeks. The primary efficacy outcome was at least 75% improvement from baseline 
in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes 
included the Investigator's Global Assessment (IGA) and PASI 90 and 50 response 
rates.
RESULTS: After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg 
resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% 
vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates 
compared with placebo were maintained throughout the follow-up period with these 
dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], 
with a gradual decline of PASI 75 response over time after the dosing period. 
IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo 
at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 
mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The 
PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. 
placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. 
Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were 
reported in the 3 × 150 mg cohort.
CONCLUSIONS: Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg 
met the primary outcome of PASI 75 response achievement after 12 weeks, 
demonstrating efficacy in moderate-to-severe psoriasis.