Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase 2/3 Japanese Study

Abstract

Introduction Certolizumab pegol (CZP), the Fc-free, PEGylated anti-tumor necrosis factor, is approved for the treatment of moderate to severe plaque psoriasis (PSO) in Western countries and in Japan, among other indications. Methods We report results from the first 16 weeks of a 52-week phase 2/3 trial of CZP in Japanese patients with PSO. Patients ≥ 20 years with PSO ≥ 6 months (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area affected ≥ 10%, and Physician’s Global Assessment [PGA] ≥ 3 on a 5-point scale) were randomized 2:2:1 to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (400 mg weeks 0/2/4), or placebo Q2W. Outcomes assessed to week 16: PASI 75, PASI 90, PGA 0/1 (Markov chain Monte Carlo), Dermatology Life Quality Index (DLQI 0/1) and Itch Numeric Rating Scale (INRS 0) (non-responder imputation), and DLQI and INRS change from baseline (last observation carried forward). Safety data were reported for patients receiving ≥ 1 dose of study medication through weeks 0–16; adverse events were evaluated using Medical Dictionary for Regulatory Activities version 18.1. Results A total of 127 patients were randomized to CZP 400 mg Q2W ( N = 53), CZP 200 mg Q2W ( N = 48), placebo ( N = 26). Week 16 responder rates for CZP 400 mg/200 mg Q2W versus placebo were 87.1%/73.0% versus 7.9% for PASI 75; 75.7%/53.8% versus 0.2% for PASI 90; 66.7%/52.7% versus 0.0% for PGA 0/1 (all p < 0.0001 for both CZP doses versus placebo). Significant improvements in DLQI and INRS were reported at week 16 by patients receiving both CZP doses compared with placebo ( p < 0.0001). Incidence of treatment-emergent adverse events within the CZP 400 mg Q2W, CZP 200 mg Q2W, and placebo groups were 326.1, 404.9, and 682.4 per 100 patient-years. No new safety signals were identified compared to previously reported data. Conclusion CZP dosed at 400 mg or 200 mg Q2W was associated with improved PSO signs and symptoms. Trial Registration ClinicalTrials.gov identifier, NCT03051217.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results

“…The efficacy of CZP during weeks 0-16 has been previously shown [21]. Among patients who were PASI 50 responders at week 16 and who received CZP treatment during the maintenance treatment period, PASI 75 responder rates were generally maintained from weeks 16 to 52 for all treatment groups, with C 85.0% PASI 75 responders in each group at week 52 (Table 2).…”

“…The primary efficacy endpoint of the study and other secondary outcomes (efficacy and safety) over 16 weeks of CZP treatment were previously reported [21]. Outcomes reported here were other outcomes of the study.…”

“…In a phase 2/3, multi-centre, randomised, double-blind, placebo-controlled Japanese clinical trial, which evaluated the safety and efficacy of CZP for the treatment of moderate to severe PSO in Japanese patients (NCT03051217), CZP dosed at 400 mg every 2 weeks (Q2W) and 200 mg Q2W over 16 weeks showed clinically meaningful improvements in moderate to severe PSO, with no new safety signals identified compared with previously reported data [21]. Here, we present 52-week outcomes from the same trial.…”

“…patient initially responded then discontinued treatment owing to loss of response after 12 weeks of treatment); a diagnosis of any inflammatory arthritis other than psoriatic arthritis; or guttate, drug-induced, erythrodermic or pustular psoriasis. Full inclusion and exclusion criteria have been published previously [21].…”

“…2 Patient disposition. Patient disposition during the initial treatment period (weeks 0-16) was previously reported [21]. CZP certolizumab pegol, Q2W every 2 weeks, Q4W every 4 weeks imputed using non-responder imputation (NRI); for mNAPSI, last observation carried forward (LOCF) was used.…”