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.

Keywords: Certolizumab pegol; Japan; Plaque psoriasis; Tumor necrosis factor-alpha.

Figures

Fig. 1

Study design. aPatients received a CZP 400 mg loading dose at weeks 0, 2 and 4; bPatients who did not achieve PASI 50 at week 16, 24, 32, or 40 entered an open-label escape arm and received CZP 200 mg Q2W (CZP 400 mg Q2W loading dose for the first three visits). Patients receiving open-label CZP 200 mg Q2W in the escape arm and not achieving a PASI 50 response were permitted to have their dose increased to CZP 400 mg Q2W, at the discretion of the investigator. CZP certolizumab pegol, LD loading dose, PASI 50 ≥ 50% improvement in from baseline in Psoriasis Area and Severity Index, Q2W every 2 weeks, Q4W every 4 weeks

Fig. 2

Patient disposition. CZP certolizumab pegol, Q2W every 2 weeks. Screen failure are reported for patients with PSO, erythrodermic psoriasis, and generalized pustular psoriasis, the reasons being ineligibility (n = 39/43; 20.3%), adverse event (n = 3/43; 1.6%) and consent withdrawn (n = 1/43; 0.5%)

Fig. 3

Efficacy outcomes to week 16 (MCMC). ap < 0.05; bp ≤ 0.0001 versus placebo; cAt weeks 4, 8, 12, and 16 exact regression was used to estimate odds ratios and simple proportions were calculated for PASI 90 responder rate. CZP certolizumab pegol, MCMC Markov chain Monte Carlo, PASI 75/90 ≥ 75%/90% improvement from baseline in Psoriasis Area and Severity Index, PGA 0/1 Physician’s Global Assessment clear/almost clear with ≥ 2-category improvement from baseline, Q2W every 2 weeks

Fig. 4

DLQI outcomes to week 16. A reduced DLQI score represents an improvement. DLQI is measured on a scale of 0–30. ap < 0.05; bp < 0.0001 versus placebo. CZP certolizumab pegol, DLQI Dermatology Life Quality Index, DLQI 0/1 achievement of a DLQI score of ≤ 1 (remission), LOCF last observation carried forward, NRI non-responder imputation, Q2W every 2 weeks

Fig. 5

INRS outcomes to week 16. A reduced INRS score represents an improvement. INRS is measured on a scale of 0–10. ap < 0.05; bp ≤ 0.0001 versus placebo. CZP certolizumab pegol, INRS Itch Numeric Rating Scale, INRS 0 achievement of an INRS score of 0 (remission), LOCF last observation carried forward, NRI non-responder imputation, Q2W every 2 weeks