Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2)

Abstract

Background: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic.

Objectives: To report the 3-year efficacy of CZP in plaque psoriasis, pooled from the CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) phase III trials.

Methods: Adults with moderate-to-severe psoriasis for ≥ 6 months were randomized 2 : 2 : 1 to CZP 200 mg, CZP 400 mg or placebo, every 2 weeks (Q2W) for up to 48 weeks. Patients entering the open-label period (weeks 48-144) from double-blinded CZP initially received CZP 200 mg Q2W. Patients not achieving ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 16 entered an open-label CZP 400 mg Q2W escape arm (weeks 16-144). Dose adjustments based on PASI response were permitted during open-label treatment. Outcomes included PASI 75, PASI 90 and Physician's Global Assessment (PGA) 0/1 responder rates, based on a logistic regression model (missing data imputed using Markov Chain Monte Carlo methodology).

Results: In total, 186 patients were randomized to CZP 200 mg Q2W and 175 to CZP 400 mg Q2W. At week 48, PASI 75/90 was achieved by 72·7%/51·3% of patients randomized to CZP 200 mg and 84·4%/62·7% randomized to CZP 400 mg. Patients entering the open-label period at week 48, from blinded treatment, received CZP 200 mg Q2W. At week 144, PASI 75/90 was achieved by 70·6%/48·7% patients randomized to CZP 200 mg and 72·9%/42·7% randomized to CZP 400 mg. At week 16, 72 placebo-randomized patients entered the CZP 400 mg Q2W escape arm; 75.7%/58.5% achieved PASI 75/90 at week 144.

Conclusions: Both CZP 200 mg and 400 mg Q2W demonstrated sustained, durable efficacy, with numerically higher responses for some outcomes with 400 mg Q2W.

© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Figures

Figure 1

The initial, maintenance and open‐label periods of the CIMPASI‐1 and CIMPASI‐2 phase III trials. CZP, certolizumab pegol; LD, loading dose [CZP 400 mg every 2 weeks (Q2W) at weeks 0, 2 and 4, or weeks 16, 18 and 20]; PASI, Psoriasis Area and Severity Index. aDose adjustments were permitted through weeks 60–132; dose escalation was mandatory in patients not achieving ≥ 50% reduction from baseline in PASI (PASI 50), and at the investigator’s discretion in patients achieving PASI 50 but not PASI 75; patients who had received CZP 400 mg Q2W for at least 12 weeks could have had their dose reduced, at the investigator’s discretion, if they achieved PASI 75, and were withdrawn if they did not achieve PASI 50. bPatients entering the open‐label period from the CZP 400 mg Q2W escape arm continued to receive CZP 400 mg Q2W but may have had their dose reduced to CZP 200 mg Q2W at week 48, at the discretion of the investigator, if they achieved PASI 75.

Figure 2

Patient disposition to week 144. The patient populations discussed in this manuscript are outlined in red. Dose adjustments during the open‐label period are described in Figure S1 (see Supporting Information). CZP, certolizumab pegol; PASI 50, ≥ 50% reduction from baseline in Psoriasis Area and Severity Index; Q2W, every 2 weeks.

Figure 3

PASI 75, PASI 90, PGA 0/1 and DLQI 0/1 responses over time. DLQI 0/1, Dermatology Life Quality Index score 0 or 1; PASI 75/90, ≥ 75%/90% improvement in Psoriasis Area and Severity Index; PGA 0/1, Physician’s Global Assessment score 0 or 1 (clear or almost clear, with ≥ 2‐point improvement from baseline). Data are presented according to initial randomization for the certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W) (a) and CZP 400 mg Q2W (b) groups, and for placebo‐randomized patients who entered the open‐label CZP 400 mg escape arm at week 16 (c). Estimates of responder rate were based on a logistic regression model, including patients who either did or did not have their dose adjusted during the open‐label period. At week 48, patients entering the open‐label period from blinded CZP 200 mg Q2W or CZP 400 mg Q2W initially received CZP 200 mg Q2W, and patients entering from the open‐label escape arm initially received CZP 400 mg Q2W (or may have had their dose reduced to CZP 200 mg Q2W at the discretion of the investigator if they achieved PASI 75). Subsequent dose adjustments were permitted through weeks 60–144. aOne patient considered to have entered the open‐label period from blinded CZP 200 mg Q2W did not receive CZP treatment from week 42 onwards and is not counted in this calculation.

Figure 4

The proportion of patients achieving clinically relevant absolute Psoriasis Area and Severity Index (PASI) thresholds: PASI aOne patient considered to have entered the open‐label period from blinded CZP 200 mg Q2W did not receive CZP treatment from week 42 onwards and is not counted in this calculation.

Figure 5

PASI 75, PASI 90 and DLQI 0/1 responses over time in patients who achieved PASI 75 after 16 weeks of certolizumab pegol (CZP) treatment. PASI 75/90, ≥ 75%/90% improvement in Psoriasis Area and Severity Index; DLQI 0/1, Dermatology Life Quality Index score 0 or 1. Data are presented for patients who achieved PASI 75 after 16 weeks of CZP treatment according to initial randomization for the CZP 200 mg every 2 weeks (Q2W) (a) and CZP 400 mg Q2W (b) groups, and for placebo‐randomized patients who entered the open‐label CZP 400 mg escape arm at week 16 (c). Estimates of responder rate were based on a logistic regression model, including patients who either did or did not have their dose adjusted during the open‐label period. At week 48, patients entering the open‐label period from blinded CZP 200 mg Q2W or CZP 400 mg Q2W initially received CZP 200 mg Q2W, and patients entering from the open‐label escape arm initially received CZP 400 mg Q2W (or may have had their dose reduced to CZP 200 mg Q2W at the discretion of the investigator if they achieved PASI 75). Subsequent dose adjustments were permitted through weeks 60–144.

Figure 6

PASI 90 (≥ 90% improvement in Psoriasis Area and Severity Index) and DLQI 0/1 (Dermatology Life Quality Index score 0 or 1) responses over time in patients who achieved PASI 90 after 16 weeks of certolizumab pegol (CZP) treatment. Data are presented for patients who achieved PASI 90 after 16 weeks of CZP treatment according to initial randomization for the CZP 200 mg every 2 weeks (Q2W) (a) and CZP 400 mg Q2W (b) groups, and for placebo‐randomized patients who entered the open‐label CZP 400 mg escape arm at week 16 (c). Estimates of responder rate were based on a logistic regression model, including patients who either did or did not have their dose adjusted during the open‐label period. At week 48, patients entering the open‐label period from blinded CZP 200 mg Q2W or CZP 400 mg Q2W initially received CZP 200 mg Q2W, and patients entering from the open‐label escape arm initially received CZP 400 mg Q2W (or may have had their dose reduced to CZP 200 mg Q2W at the discretion of the investigator if they achieved PASI 75). Subsequent dose adjustments were permitted through weeks 60–144.