Maintenance of response with certolizumab pegol for the treatment of chronic plaque psoriasis: 48-week results from two ongoing Phase III, multicenter, randomized, placebo-controlled studies (CIMPASI-1 and CIMPASI-2)
Presenters: Reich K1, Blauvelt A2, Thaçi D3, Leonardi C4, Poulin Y5, Burge D6, Peterson L7, Drew J6, Arendt C8, Gottlieb AB9
Affiliations: 1Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany; 2Oregon Medical Research Center, Portland, OR; 3University of Lübeck, Lübeck, Germany; 4Central Dermatology and Saint Louis University School of Medicine, St. Louis, MO; 5Centre de Recherche Dermatologique du Québec Métropolitain, Québec, Canada; 6Dermira, Inc., Menlo Park, CA; 7UCB BioSciences, Inc., Raleigh, NC; 8UCB Pharma, Brussels, Belgium; 9New York Medical College, Valhalla, NY
Introduction: Psoriasis affects approximately three percent of adults in the United States and approximately 2 to 6 percent in Europe, and most patients develop the disease in the third decade of life. Therapy for patients with chronic plaque psoriasis varies per the severity of the disease, with topical therapies and/or phototherapy used to treat limited or mild psoriasis, and photochemotherapy, cyclosporine, methotrexate, apremilast, or biologics (e.g., tumor necrosis factor (TNF) inhibitors,
anti?IL17s, and anti?IL12/23s) used to treat moderate-to-severe forms. Certolizumab pegol (CZP) is the only PEGylated, Fc-free, anti-TNF biologic currently under development for the treatment of moderate-to-severe chronic plaque psoriasis and has demonstrated positive results in previous psoriasis trials. CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) are ongoing Phase III trials designed to assess the efficacy and safety of CZP compared with placebo; results from the first 48 weeks of the two studies are presented here.
Methods: CIMPASI-1 and CIMPASI-2 are replicate, Phase III multicenter studies conducted in North America and Europe, consisting of randomized, double-blind, placebo-controlled periods for the first 48 weeks followed by 96 weeks of open-label observation. Patients were randomized 2:2:1 to CZP 400mg every two weeks (Q2W), CZP 200mg Q2W (following 400mg loading dose at Weeks 0, 2, 4), or placebo Q2W for 16 weeks. At Week 16, the following patients continued to receive treatment through Week 48: CZP 400mg Q2W- and CZP 200mg Q2W-treated Psoriasis Area and Severity Index (PASI) 50 responders (?50% reduction in PASI) continued to receive their initial blinded treatment; placebo-treated Week 16 PASI 75 responders (?75% reduction in PASI) continued blinded placebo treatment; PASI 50 to 75 responders (?50% but <75% reduction in PASI) received CZP 200mg Q2W (following 400mg loading dose at Weeks 16, 18, 20); PASI 50 nonresponders at Week 16 entered the Escape Arm and received unblinded CZP 400mg Q2W; PASI 50 nonresponders at Week 32, 40, or 48 were withdrawn from the study. Eligible patients were at least 18 years of age and had moderate-to-severe chronic plaque psoriasis for at least six months (PASI ?12, Body Surface Area (BSA) ?10%, Physician’s Global Assessment [PGA; 5-point scale] ?3). Patients had to be candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy. Patients were excluded if they had previous treatment with CZP or more than two biologics (including anti-TNF); had history of primary failure to any biologic or secondary failure to more than one biologic; had erythrodermic, guttate, or generalized pustular psoriasis types; or had history of current, chronic, or recurrent viral, bacterial, or fungal infections. Coprimary endpoints were PASI 75 and PGA 0/1 (“clear” or “almost clear” with ?2-category improvement) at Week 16. Secondary endpoints reported here were PASI 90 at Week 16 and PASI 75 and PGA 0/1 at Week 48; PASI 90 at Week 48 was included as an additional endpoint. All efficacy analyses were performed on the Randomized Set (all randomized patients). Logistic regression models with factors of treatment group, region, and prior biologic exposure (yes/no) were used to analyze PASI 75, PGA 0/1, and PASI 90 responder rates (Week 16). The Markov chain Monte Carlo (MCMC) method for multiple imputation was used to account for missing data. Safety assessments were performed on the Safety Set, which included all randomized patients who received at least one dose of study medication.
Results: In both studies, at least 90 percent of patients in each treatment arm completed Week 16, and the highest Week 16 completion rates were in the CZP 400mg Q2W treatment group. Of those patients who entered the blinded Maintenance Period in CIMPASI-1/CIMPASI-2, 90.9 percent/88.4 percent of CZP 400mg Q2W patients and 95.9 percent/84.2 percent CZP 200mg Q2W patients completed Week 48. Baseline PASI and PGA scores were comparable across treatment groups for both studies. Roughly one-third of study participants reported prior biologic use, and the proportion across treatment arms was similar. At Week 16, responder rates were greater for CZP 400mg Q2W and CZP 200mg Q2W versus placebo for PASI 75 and PGA 0/1 (p<0.0001 for all). CZP 400mg Q2W and CZP 200mg Q2W PASI 75 responder rates were maintained to Week 48. PGA 0/1 responder rates were also maintained to Week 48 for patients who continued to receive either dose of CZP during the Maintenance Period. At Week 16, PASI 90 responder rates were greater for CZP 400mg Q2W and 200mg Q2W versus placebo (p<0.0001 for both). PASI 90 responder rates continued to improve beyond Week 16, and the difference between dose groups increased by Week 48. For CZP 400mg Q2W and CZP 200mg Q2W versus placebo, treatment-emergent adverse events (TEAE)/serious TEAE incidence rates per 100 patient?years from baseline to Week 16 were 375.9/19.0 and 292.3/6.9 versus 297.1/6.8 in CIMPASI-1, and 405.7/15.3 and 308.7/7.4 versus 388.9/0 in CIMPASI-2. For CZP 400mg Q2W and CZP 200mg Q2W, TEAE/serious TEAE incidence rates per 100 patient-years was lower from baseline to Week 48 compared with rates per 100 patient-years from baseline to Week 16 (257.6/10.4 and 218.3/5.3 in CIMPASI-1, and 277.5/7.5 and 236.0/9.7 in CIMPASI-2). One serious infection was reported in the CZP 400mg Q2W group in CIMPASI-1, and one in the
CZP 400mg Q2W group in CIMPASI-2. One death, due to motor vehicle accident, was reported in the
CZP 400mg Q2W group in CIMPASI?1. After 48 weeks of treatment, TEAEs occurring in over 10 percent of all CZP-treated patients were nasopharyngitis and upper respiratory tract infection.
Conclusion: Treatment with CZP 400mg Q2W or CZP 200mg Q2W for 16 weeks was associated with statistically significant, clinically meaningful improvements for all endpoints analyzed (PASI 75, PGA 0/1, and PASI 90) compared to placebo. Response rates were maintained at Week 48 with both CZP doses. For most measures, improvement at both Week 16 and Week 48 was numerically greatest in patients receiving CZP 400mg Q2W. TEAEs were consistent with the known safety profile of anti-TNF therapy, and no new safety signals were observed with CZP at any dose over 48 weeks.
Funding/Disclosures: This study and all costs associated with the development of this poster were funded by Dermira, Inc. Andrew Blauvelt and Diamant Thaçi receive consulting honoraria, are clinical investigators for and/or receive speaker’s fees from Dermira, Inc. Daniel Burge and Janice Drew are employees of Dermira, Inc. Alice B. Gottlieb holds consulting and/or advisory board agreements with Dermira, Inc.