Secukinumab is Superior to Ustekinumab in Clearing Skin in Patients with Moderate to Severe Plaque Psoriasis (16-Week CLARITY Results)

Abstract

Introduction: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.

Methods: In the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator's Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.

Results: Both co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).

Conclusion: The results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.

Trial registration: Clinicaltrials.gov Identifier, NCT02826603.

Funding: Novartis Pharma AG, Basel, Switzerland.

Keywords: Moderate to severe psoriasis; Secukinumab; Ustekinumab.

Fig. 1

Study design of the CLARITY study. ^¥Ustekinumab dose is based on body weight at baseline; 45 mg for patient ≤ 100 kg; 90 mg for patient > 100 kg. ^†For patients with premature treatment discontinuation only. F4 = follow-up visit approximately 4 weeks after the EOT visit. F8 = follow-up visit approximately 8 weeks after the EOT visit. ↓ = active dose administration; in order to maintain blinding, patients received placebo administrations at several time points (not shown in this study design figure). The screening phase duration was at least 2 weeks and up to 4 weeks. BL baseline, EOT end of treatment phase

Fig. 2

Patient disposition

Fig. 3

PASI 90 (a), IGA mod 2011 0/1 (b), and PASI 100 (c) responses out to Week 16. Missing values handled by multiple imputation. IGA mod 2011 0/1 Investigator’s Global Assessment, 2011 modification, clear (0) or almost clear (1) score, PASI 90 Psoriasis Area and Severity Index 90% improvement vs. Baseline, PASI 100 Psoriasis Area and Severity Index 100% improvement vs Baseline. *p < 0.0001

Fig. 4

DLQI 0/1 response out to Week 16. Missing values handled by last observation carried forward. DLQI 0/1 Dermatology Life Quality Index 0/1 (representing no impact of skin disease on patients’ quality of life). *p < 0.0001