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

Abstract

Introduction: Certolizumab pegol (CZP), an Fc-free, PEGylated anti-tumour necrosis factor biologic, dosed at 400 mg every 2 weeks (Q2W) and 200 mg Q2W over 16 weeks, resulted in improvements in Japanese patients with moderate to severe plaque psoriasis (PSO); no new safety signals were identified. We present 52-week efficacy and safety results.

Methods: Patients ≥ 20 years with PSO ≥ 6 months [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area ≥ 10%, Physician's Global Assessment (PGA) ≥ 3] were randomised 1:2:2 to placebo Q2W, CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks. Week 16 PASI 50 responders continued through week 52; CZP 200 mg Q2W-randomised patients were re-randomised 1:1 to CZP 200 mg Q2W or CZP 400 mg Q4W; patients initially randomised to other treatment groups continued in the same group. Outcomes included PASI 75/90/100, PGA 0/1, Dermatology Life Quality Index (DLQI) 0/1, Itch Numeric Rating Scale (INRS) 0, modified Nail Psoriasis Severity Index (mNAPSI), durability of response for week 16 PASI 75/90 responders, and safety.

Results: Of 26/53/48 patients randomised to placebo, CZP 400 mg Q2W and CZP 200 mg Q2W, 2/47/39 completed week 52, respectively. PASI 75/90 responses were generally maintained from weeks 16 to 52 for all CZP doses. Most week 16 PASI 75/90 achievers maintained their response through week 52. PASI 75/90/100 responses at week 52 in the CZP 400 mg Q2W and CZP 200 mg Q2W groups were 83.0/81.1/41.5% and 72.9/60.4/18.8%, respectively; DLQI/INRS remission rates were 64.2/50.9% in CZP 400 mg Q2W and 58.3/27.1% in CZP 200 mg Q2W-treated patients. Reductions in mNAPSI observed for CZP-treated groups were maintained through week 52. No new safety signals were identified.

Conclusion: CZP treatment resulted in improvements in signs and symptoms of PSO, which were maintained through week 52. The 400 mg Q2W dose could provide additional clinical benefit.

Trial registration: NCT03051217.

Keywords: Anti-tumour necrosis factor; Certolizumab pegol; Japanese patients; Maintenance therapy; Plaque psoriasis.

Figures

Fig. 1

Study design. aPatients received a loading dose of CZP 400 mg at weeks 0, 2 and 4; bpatients initially randomised to CZP 200 mg Q2W were re-randomised (1:1) to receive either CZP 200 mg Q2W or CZP 400 mg Q4W (with placebo administered on alternate dosing weeks to maintain the blind); cpatients who achieved PASI 50 continued therapy to week 52; dpatients who did not achieve PASI 50 entered an open-label escape arm and received CZP 200 mg Q2W (CZP 400 mg Q2W loading dose for the first three visits). CZP certolizumab pegol, LD loading dose, PASI 50  ≥ 50% reduction from baseline in Psoriasis Area and Severity Index, Q2W every 2 weeks, Q4W every 4 weeks

Fig. 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

Fig. 3

Durability of response. Responder rates are summarised according to patients’ blinded maintenance treatment group. Missing values were imputed using NRI. Placebo data are not shown as there were only two patients in the placebo group who were week 16 PASI 75 responders and no patients in the placebo group were week 16 PASI 90 responders. aIncludes patients who received CZP 200 mg Q2W and CZP 400 mg Q4W during maintenance. CZP certolizumab pegol, NRI non-responder imputation, PASI 75/90 at least 75%/90% improvement from baseline in Psoriasis Area and Severity Index, Q2W every 2 weeks, Q4W every 4 weeks

Fig. 4

Efficacy outcomes to week 52. Responder rates are summarised according to patients’ originally randomised treatment group. Missing values were imputed using NRI. aOnly four patients continued placebo treatment in maintenance; therefore, placebo data are only shown to week 16; bincludes patients who received CZP 200 mg Q2W and CZP 400 mg Q4W during maintenance. CZP certolizumab pegol, NRI non-responder imputation, PASI75/90 at least 75%/90% improvement from baseline in Psoriasis Area and Severity Index, PGA 0/1 Physician's Global Assessment (‘clear’ or ‘almost clear’ with ≥ 2-point improvement from baseline), Q2W every 2 weeks, Q4W every 4 weeks

Fig. 5

Other efficacy outcomes to week 52. Responder rates and mean change from baseline are summarised according to patients’ originally randomised treatment group. Missing values were imputed using NRI (for DLQI and INRS) and LOCF for mNAPSI. aOnly four patients continued placebo treatment in maintenance; therefore, placebo data are only shown to week 16; bincludes patients who received CZP 200 mg Q2W and CZP 400 mg Q4W during maintenance; cmNAPSI was assessed only in patients with psoriatic nail disease at baseline. CfB change from baseline, CZP certolizumab pegol, DLQI Dermatology Life Quality Index, INRS Itch Numeric Rating Scale, mNAPSI modified Nail Psoriasis Severity Index, NRI non-responder imputation, Q2W every 2 weeks, Q4W every 4 weeks, SD standard deviation