Risankizumab vs. ustekinumab for plaque psoriasis: a critical appraisal.

AIM: Gordon et al. investigated the efficacy and safety of risankizumab [an anti-interleukin (IL)-23p19 biologic] compared with ustekinumab (anti-IL-12/23p40) and placebo in patients with moderate-to-severe chronic plaque psoriasis. This was a parallel-group controlled study up to 16 weeks with a planned switch of the placebo group to risankizumab at 16 weeks.

SETTING AND DESIGN: This study consisted of two replicate phase III, double-blinded randomized controlled trials (UltIMMa-1 and UltIMMa-2) conducted across 139 centres in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain and the U.S.A.

STUDY EXPOSURE: Patients with a minimum 6-month history of chronic plaque psoriasis were randomly assigned to receive either 150 mg risankizumab, 45 mg or 90 mg ustekinumab or placebo. Prior to this, each group was also stratified by weight (either more than or less than 100 kg) and previous exposure to tumour necrosis factor inhibitors. Those assigned to receive placebo were transitioned onto risankizumab at week 16. The study drugs were given at weeks 0, 4, 16, 28 and 40.

OUTCOMES: The severity of psoriasis was measured using the Psoriasis Area and Severity Index (PASI) and a static Physician's Global Assessment (sPGA). The authors additionally recorded the number of adverse events in each treatment arm, and a measure of quality of life.

PRIMARY OUTCOME MEASURES: The coprimary outcomes were the proportions of patients achieving ≥ 90% reduction in their baseline PASI (PASI 90) and an sPGA score of 0 or 1 (clear or almost clear) at week 16.

RESULTS: In total 506 patients were included in UltIMMa-1 and 491 patients in UltIMMa-2. In UltIMMa-1, PASI 90 by week 16 was achieved by 75·3% of patients receiving risankizumab, compared with 42·0% receiving ustekinumab and 4·9% receiving placebo (P < 0·001 vs. placebo and ustekinumab). sPGA of 0 or 1 by week 16 was achieved by 87·6% of patients receiving risankizumab, compared with 63·0% receiving ustekinumab and 7·8% receiving placebo (P < 0·001 vs. placebo and ustekinumab). The results for UltIMMa-2 are similar. The frequencies of adverse events in the risankizumab, ustekinumab and placebo groups were similar in both studies.

CONCLUSIONS: Gordon et al. conclude that risankizumab has a higher efficacy than placebo and ustekinumab in the treatment of moderate-to-severe chronic plaque psoriasis, and that the adverse-event profiles were similar across all treatment groups.