Efficacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, open-label, efficacy-assessor-blinded clinical trial

Abstract

Background: Patients with plaque psoriasis treated with biologic therapies need more efficacious, safe and convenient treatments to improve quality of life. Risankizumab and secukinumab inhibit interleukin-23 and interleukin-17A, respectively, and are effective in adult patients with moderate-to-severe plaque psoriasis but have different dosing regimens.

Objectives: To compare directly the efficacy and safety of risankizumab vs. secukinumab over 52 weeks.

Methods: IMMerge was an international, phase III, multicentre, open-label, efficacy-assessor-blinded, active-comparator study, in which adult patients with chronic, moderate-to-severe plaque psoriasis were randomized in a 1 : 1 ratio to treatment with risankizumab 150 mg or secukinumab 300 mg. Primary efficacy endpoints were the proportions of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at week 16 (noninferiority comparison with margin of 12%) and week 52 (superiority comparison).

Results: In total 327 patients from nine countries were treated with risankizumab (n = 164) or secukinumab (n = 163). Risankizumab was noninferior to secukinumab in the proportion of patients achieving PASI 90 at week 16 [73·8% vs. 65·6%; difference of 8·2%, 96·25% confidence interval (CI)-2·2 to 18·6; within the 12% noninferiority margin] and superior to secukinumab at week 52 (86·6% vs. 57·1%; difference of 29·8%, 95% CI 20·8-38·8; P < 0·001), thus meeting both primary endpoints. All secondary endpoints (PASI 100, static Physician's Global Assessment 0 or 1, and PASI 75) at week 52 demonstrated superiority for risankizumab vs. secukinumab (P < 0·001). No new safety concerns were identified.

Conclusions: At week 52, risankizumab demonstrated superior efficacy and similar safety with less frequent dosing compared with secukinumab.

Figure 1

Study design. The hatched area from week 52 to week 64 corresponds to two additional doses administered to patients in France. The additional doses did not affect efficacy assessments performed at week 52.

Figure 2

Patient disposition. ^aSome patients had discontinued the study drug as described below.

Figure 3

Primary efficacy results. Proportions of patients with ≥ 90% reduction in Psoriasis Area and Severity Index (PASI 90) at week 16 and week 52. Risankizumab was noninferior to secukinumab at week 16 based on a noninferiority margin of 12%, and superior to secukinumab at week 52 (P < 0·001). Data were assessed for the intent‐to‐treat population. The adjusted‐difference confidence interval (CI) values were 96·25% CI at week 16 and 95% CI at week 52. P‐values were calculated from the Cochran–Mantel–Haenszel test, stratified by weight (≤ 100 kg vs. > 100 kg) and prior systemic biologic use for psoriasis. Nonresponder imputation was used for missing data.

Figure 4

Secondary efficacy results. Proportions of patients achieving (a) 100% reduction in Psoriasis Area and Severity Index (PASI 100), (b) static Physician’s Global Assessment (sPGA) of 0 or 1 and (c) PASI 75 at week 52. Significantly more patients treated with risankizumab achieved all secondary endpoints than did patients treated with secukinumab (P < 0·001), demonstrating superiority of risankizumab over secukinumab. Secondary endpoints (week 52) are indicated by the boxed regions. Data were assessed for the intent‐to‐treat population. The adjusted‐difference confidence interval was set at 95%. P‐values were calculated from the Cochran–Mantel–Haenszel test, stratified by weight (≤ 100 kg vs. > 100 kg) and prior systemic biologic use for psoriasis. Nonresponder imputation was used for missing data.