Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results

Abstract

Introduction: We report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217).

Methods: Patients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved "much improved" or "very much improved" on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician's Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0-52.

Results: Of 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response ("improved" or "remission"). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients.

Conclusion: CZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified.

Trial registration: ClinicalTrials.gov identifier, NCT03051217.

Keywords: Anti-tumor necrosis factor; Certolizumab pegol; Erythrodermic psoriasis; Generalized pustular psoriasis; Japan.

© 2022. The Author(s).

Figures

Fig. 1

Study design. aPatients who achieved “much improved” or “very much improved” in GIS (GPP) or a PASI 50 response (EP) continued therapy to week 52; bPatients received a CZP 400 mg loading dose at weeks 0, 2, and 4; cPatients in the CZP 200 mg Q2W group who failed to achieve a response could have their dose increased to CZP 400 mg Q2W, at the discretion of the investigator. In the opinion of the investigator, if the patient failed to achieve a response with the CZP 400 mg Q2W dose, the patient could be withdrawn from the study; de.g., methotrexate, cyclosporine, azathioprine; eAt a daily dose of ≤ 10 mg/day of prednisone or its equivalent. CZP certolizumab pegol, EP erythrodermic psoriasis, GIS Global Improvement Score, GPP generalized pustular psoriasis, LD loading dose, PASI 50 ≥ 50% reduction from baseline in Psoriasis Area and Severity Index, Q2W every 2 weeks

Fig. 2

Patient disposition to week 52. aThree patients (one with GPP and two with EP) who had received CZP 200 mg Q2W during the initial treatment period were not in response during the maintenance treatment period, and their dose was increased to CZP 400 mg Q2W. CZP certolizumab pegol, EP erythrodermic psoriasis, GPP generalized pustular psoriasis, Q2W every 2 weeks

Fig. 3

CGI-I response in patients with GPP and EP at weeks 16 and 52 of CZP treatment. Full analysis set. Observed case. Data summarized according to patients’ originally randomized treatment group at week 0. Total n at each timepoint may vary, being the summation of the number of patients who were responders and nonresponders. CGI-I responders defined as patients who achieved “remission” or “improved.” CGI-I Clinical Global Impression of Improvement, CZP certolizumab pegol, EP erythrodermic psoriasis, GPP generalized pustular psoriasis, Q2W every 2 weeks

Fig. 4

DLQI 0/1 in patients with GPP and EP at weeks 16 and 52 of CZP treatment. Full analysis set. Observed case. Data summarized according to patients’ originally randomized treatment group at week 0. Total n at each time point may vary, being the summation of the number of patients who were responders and nonresponders. DLQI 0/1 defined as patients who had absolute DLQI score of ≤ 1. CZP certolizumab pegol, DLQI Dermatology Life Quality Index, EP erythrodermic psoriasis, GPP generalized pustular psoriasis, Q2W every 2 weeks, SD standard deviation

Fig. 5

INRS absolute score in patients with GPP and EP over weeks 0–52. Full analysis set. Observed case. Data summarized according to the treatments that patients received. aNo SD available as n = 1. CZP certolizumab pegol, EP erythrodermic psoriasis, GPP generalized pustular psoriasis, INRS Itch Numeric Rating Scale, Q2W every 2 weeks, SD standard deviation

Fig. 6

JDA total score in patients with GPP over weeks 0–52. GPP set. Observed case. Data summarized according to the treatments that patients received. aNo SD available as n = 1. CZP certolizumab pegol, GPP generalized pustular psoriasis, JDA Japanese Dermatological Association, Q2W every 2 weeks, SD standard deviation

Fig. 7

Absolute PASI in patients with EP over weeks 0–52. EP set. Observed case. Data summarized according to the treatments that patients received. CZP certolizumab pegol, EP erythrodermic psoriasis, PASI Psoriasis Area and Severity Index, Q2W every 2 weeks