Poster presented at the Presented at the 36th Fall Clinical Dermatology Conference | Las Vegas, NV | October 12-15, 2017 Maintenance of Response With Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: 48-Week Results From Two Ongoing Phase 3, Multicenter, Randomized, Placebo-Controlled Studies (CIMPASI-1 and CIMPASI-2) Kristian Reich,1 Andrew Blauvelt,2 Diamant Thaçi,3 Craig Leonardi,4 Yves Poulin,5 Daniel Burge,6 Luke Peterson,7 Janice Drew,6 Catherine Arendt,8 Alice B. Gottlieb9 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 ~3% of adults in the US1,2 and ~2-6% in Europe,3 and most patients develop the disease in the third decade of life4 • 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 such as 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 trials5,6 • CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) are ongoing phase 3 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 Study Design • CIMPASI-1 and CIMPASI-2 are replicate, phase 3, 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 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (following 400 mg loading dose at Weeks 0, 2, 4), or placebo Q2W for 16 weeks (Figure 1) • At Week 16, patients continued to receive treatment through Week 48 according to the following criteria: – CZP 400 mg Q2W- and CZP 200 mg 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 50-75 responders (≥50% but <75% reduction in PASI) received CZP 200 mg Q2W (following 400 mg loading dose at Weeks 16, 18, 20) – PASI 50 nonresponders at Week 16 entered the Escape Arm and received unblinded CZP 400 mg Q2W • PASI 50 nonresponders at Week 32, 40, or 48 were withdrawn from the study Figure 1. Study Design 0 Randomization 16 484032Week Initial Treatment Period (Double-Blind) Maintenance Period (Double-Blind)Screening 1:2:2 2 4 Placebo Q2W LD ≥ PASI 75 LD PASI 50-75 < PASI 50-Withdrawn < PASI 50-Withdrawn < PASI 50-Withdrawn < PASI 50-Withdrawn < PASI 50 < PASI 50 < PASI 50 CZP 200 mg Q2W CZP 400 mg Q2W Escape CZP 400 mg Q2W CZP, certolizumab pegol; LD, CZP 400 mg loading dose at Weeks 0, 2 and 4 or Weeks 16, 18 and 20; PASI 50, ≥50% reduction in psoriasis area and severity index (PASI); PASI 50-75, ≥50% but <75% reduction in PASI; PASI 75, ≥75% reduction in PASI; Q2W, every 2 weeks Patients • Eligible patients were ≥18 years of age and had moderate-to-severe chronic plaque psoriasis for ≥6 months (PASI ≥12, affected 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 >2 biologics (including anti-TNF); had history of primary failure to any biologic or secondary failure to >1 biologic; had erythrodermic, guttate, or generalized pustular psoriasis types; or had history of current, chronic, or recurrent viral, bacterial, or fungal infections Study Assessments • 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 • Safety evaluation included assessment of treatment-emergent adverse events (TEAEs) Statistical Analysis • 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 data7 • Safety assessments were performed on the Safety Set, which included all randomized patients who received ≥1 dose of study medication RESULTS Patient Disposition, Demographics, and Baseline Characteristics • In both studies, at least 90% of patients in each treatment arm completed Week 16, and the highest Week 16 completion rates were in the CZP 400 mg Q2W treatment group (Figure 2) • Of those patients who entered the blinded Maintenance Period in CIMPASI-1|CIMPASI-2, 90.9%|88.4% of CZP 400 Q2W patients and 95.9%|84.2% CZP 200 mg Q2W patients completed Week 48 (Figure 2) • Baseline PASI and PGA scores were comparable across treatment groups for both studies (Table 1) • Roughly one-third of study participants reported prior biologic use, and the proportion across treatment arms was similar (Table 1) Figure 2. Patient Disposition Completed Wk 16 CIMPASI-1 CIMPASI-2Screened N=286 Randomized N=234 Screened N=301 Randomized N=227 Placebo N=51 N=46 (90.2%) Discontinued 5 Adverse event 0 Lack of efficacy 1 Protocol violation 0 Lost to follow-up 1 Consent w/d 3 Other 0 Discontinued 3 Adverse event 0 Lack of efficacy 0 Protocol violation 0 Lost to follow-up 1 Consent w/d 2 Other 0 Discontinued 1 Adverse event 1 Lack of efficacy 0 Protocol violation 0 Lost to follow-up 0 Consent w/d 0 Other 0 Discontinued 4 Adverse event 0 Lack of efficacy 0 Protocol violation 0 Lost to follow-up 1 Consent w/d 3 Other 0 Discontinued 7 Adverse event 3 Lack of efficacy 0 Protocol violation 0 Lost to follow-up 2 Consent w/d 2 Other 0 Discontinued 4 Adverse event 1 Lack of efficacy 0 Protocol violation 0 Lost to follow-up 0 Consent w/d 1 Other 2 CZP 200 mg Q2W N=95 ≥PASI 50 and Entered Maintenance Completed Wk48 Discontinued 3 Consent w/d 1 Other 1 1 prior biologic but ≤2 per exclusion criteria BMI, body mass index; BSA, body surface area; CZP, certolizumab pegol; DLQI, Dermatology Life Quality Index; IL, interleukin; PASI, psoriasis area and severity index; PGA, physician’s global assessment; PsA, psoriatic arthritis; Q2W, every 2 weeks; TNF, tumor necrosis factor Coprimary Endpoints • At Week 16, responder rates were greater for CZP 400 mg Q2W and 200 mg Q2W versus placebo for PASI 75 and PGA 0/1 (p<0.0001 for all) (Figure 3, Figure 4) Secondary Endpoints • CZP 400 mg Q2W and 200 mg Q2W PASI 75 responder rates were maintained to Week 48 (Figure 3) • 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 (Figure 4) • At Week 16, PASI 90 responder rates were greater for CZP 400 mg Q2W and 200 mg Q2W versus placebo (p<0.0001 for both) (Figure 5) • PASI 90 responder rates continued to improve beyond Week 16 and the difference between dose groups increased by Week 48 in CIMPASI-1 (Figure 5) Figure 3. PASI 75 Responder Rates From Baseline to Week 48 CIMPASI-1 Week Week CIMPASI-2 80 100 60 40 20 0 R es po nd er R at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 80 100 60 40 20 0 R es po nd er R at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 Placebo (N=51) CZP 200 mg Q2Wa (N=95) CZP 400 mg Q2W (N=88) 6.5% 11.6% Placebo (N=49) CZP 200 mg Q2Wa (N=91) CZP 400 mg Q2W (N=87) 66.5% 67.2% 81.4% 78.7% 75.8% 87.1% 82.6% 81.3% *p<0.05, **p<0.0001 versus placebo aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 Based on logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no) Week 16 PASI 50 nonresponders were imputed as nonresponders throughout the Maintenance period; all other missing data were imputed via multiple imputation (MCMC method) CZP, certolizumab pegol; MCMC, Markov chain Monte Carlo; PASI 75, ≥75% reduction in psoriasis area and severity index; Q2W, every 2 weeks Figure 4. PGA 0/1 Responder Rates From Baseline to Week 48 CIMPASI-1 Week Week CIMPASI-2 80 100 60 40 20 0 R es po nd er R at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 80 100 60 40 20 0 R es po nd er R at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 Placebo (N=51) CZP 200 mg Q2Wa (N=95) CZP 400 mg Q2W (N=88) 4.2% 2.0% Placebo (N=49) CZP 200 mg Q2Wa (N=91) CZP 400 mg Q2W (N=87) 47.0% 52.7% 66.8% 72.6% 57.9% 69.5% 71.6% 66.6% *p<0.05, **p<0.0001 versus placebo aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 Based on logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no) Week 16 PASI 50 nonresponders were imputed as nonresponders throughout the Maintenance period; all other missing data were imputed via multiple imputation (MCMC method) CZP, certolizumab pegol; MCMC, Markov chain Monte Carlo; PGA 0/1, ‘clear’ or ‘almost clear’ with ≥2 category improvement (on 5-point scale) in physician’s global assessment; Q2W, every 2 weeks Figure 5. PASI 90 Responder Rates From Baseline to Week 48 CIMPASI-1 Week Week CIMPASI-2 80 100 60 40 20 0 R es po nd er R at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 80 100 60 40 20 0 R es po nd er R at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 Placebo (N=51) CZP 200 mg Q2Wa (N=95) CZP 400 mg Q2W (N=88) 0.4% 4.5% Placebo (N=49) CZP 200 mg Q2Wa (N=91) CZP 400 mg Q2W (N=87) 35.8 42.8% 52.6% 59.6% 43.6% 60.2% 55.4% 62.0% *p<0.05, **p<0.0001 versus placebo aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 Based on logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no) Week 16 PASI 50 nonresponders were imputed as nonresponders throughout the Maintenance period; all other missing data were imputed via multiple imputation (MCMC method) CZP, certolizumab pegol; MCMC, Markov chain Monte Carlo; PASI 90, ≥90% reduction in psoriasis area and severity index; Q2W, every 2 weeks Safety • For CZP 400 mg Q2W and 200 mg Q2W vs placebo, TEAE|serious TEAE incidence rates per 100 patient-years from Baseline to Week 16 were 375.9|19.0 and 292.3|6.9 vs 297.1|6.8 in CIMPASI-1, and 405.7|15.3 and 308.7|7.4 vs 388.9/0 in CIMPASI-2 • For CZP 400 mg Q2W and 200 mg 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) (Table 2) • One serious infection was reported in the CZP 400 mg Q2W group in CIMPASI-1, and one in the CZP 400 mg Q2W group in CIMPASI-2; one death, due to motor vehicle accident, was reported in the CZP 400 mg Q2W group in CIMPASI-1 (Table 2) • After 48 weeks of treatment, TEAEs occurring in >10% of all CZP-treated patients were nasopharyngitis and upper respiratory tract infection (Table 3) Table 2. Adverse Events From Baseline to Week 48 CIMPASI-1 CIMPASI-2 CZP 200 mg Q2W (N=100)g CZP 400 mg Q2W (N=144)g CZP 200 mg Q2W (N=95)g CZP 400 mg Q2W (N=129)g TEAEs, n (%) [incidence ratea] All 72 (72.0) [218.3] 111 (77.1) [257.6] 73 (76.8) [236.0] 103 (79.8) [277.5] Serious 4 ( 4.0) [ 5.3] 11 ( 7.6) [ 10.4] 7 ( 7.4) [ 9.7] 7 ( 5.4) [ 7.5] Discontinuations due to TEAE, n (%)b 0 5 (3.5) 8 (8.4) 8 (6.2) Deaths, n (%)b 0 1 (0.7) 0 0 TEAEs of interest, n (%) [incidence ratea] Infections and infestations 50 (50.0) [102.5] 76 (52.8) [115.9] 48 (50.5) [98.1] 68 (52.7) [111.2] Latent tuberculosis 0 1 ( 0.7) [ 0.9] 0 0 Active tuberculosis 0 0 0 0 Candida infections 1 ( 1.0) [ 1.3]c 0 1 ( 1.1) [ 1.4]d 2 ( 1.6) [ 2.1]d,e Oral fungal infection 0 0 0 1 ( 0.8) [ 1.0] Fungal skin infection 0 1 ( 0.7) [ 0.9] 0 0 Herpes Zoster 0 0 1 ( 1.1) [ 1.4] 0 Herpes dermatitis 0 0 0 1 ( 0.8) [ 1.0] Epstein-Barr viral infection 0 0 1 ( 1.1) [ 1.4] 0 Serious infections 0 1 ( 0.7) [ 0.9] 0 1 ( 0.8) [ 1.1] Non-melanoma skin cancerf 0 1 ( 0.7) [ 0.9] 0 1 ( 0.8) [ 1.1] Malignancy (excluding non-melanoma skin cancer) 0 0 0 0 IBD flare 0 0 0 0 Depression 0 2 ( 1.4) [ 1.8] 1 ( 1.1) [ 1.4] 2 ( 1.6) [ 2.1] aIncidence of new cases per 100 subject-years bIncidence rate not calculated cOral candidiasis dVulvovaginal candidiasis eNail Candida fBoth malignancies were basal cell carcinomas gPatients who switched doses could have been counted in both CZP doses Patients initially randomized to CZP 200 mg Q2W who received CZP 400 mg Q2W in the Escape Arm were counted in both CZP doses CZP, certolizumab pegol; IBD, inflammatory bowel disease; TEAE, treatment-emergent adverse event Table 3. Most Frequently Reported TEAEs (≥5% in Any Group): Baseline to Week 48 n (%), [incidence ratea] CIMPASI-1 CIMPASI-2 CZP 200 mg Q2W (N=100)b CZP 400 mg Q2W (N=144)b CZP 200 mg Q2W (N=95)b CZP 400 mg Q2W (N=129)b Nasopharyngitis 28 (28.0) [46.5] 40 (27.8) [46.9] Nasopharyngitis 17 (17.9) [26.4] 25 (19.4) [29.0] URTI 12 (12.0) [17.2] 13 ( 9.0) [12.8] URTI 11 (11.6) [16.1] 13 (10.1) [14.5] Arthralgia 6 ( 6.0) [ 8.2] 2 ( 1.4) [ 1.8] Hypertension 5 ( 5.3) [ 7.2] 8 ( 6.2) [ 8.6] Headache 6 ( 6.0) [ 8.2] 12 ( 8.3) [11.7] Urinary tract infection 5 ( 5.3) [ 7.1] 5 ( 3.9) [ 5.3] Pruritus 2 ( 2.1) [ 2.8] 8 ( 6.2) [ 8.8] Pharyngitis 6 ( 6.3) [ 8.5] 3 ( 2.3) [ 3.2] Bronchitis 2 ( 2.1) [ 2.8] 7 ( 5.4) [ 7.5] aIncidence of new cases per 100 subject-years bPatients who switched doses could have been counted in both CZP doses Patients initially randomized to CZP 200 mg Q2W who received CZP 400 mg Q2W in the Escape Arm were counted in both CZP doses CZP, certolizumab pegol; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection CONCLUSIONS • Treatment with CZP 400 mg Q2W or CZP 200 mg 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 with 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 400 mg 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 References 1. Rachakonda et al. J Am Acad Dermatol. 2014;70(3):512-6. 2. Kurd et al. J Am Acad Dermatol. 2009;60(2):218-24. 3. Danielsen et al. Br J Dermatol. 2013;168(6):1303-10. 4. Farber et al. Dermatologica. 1974;148(1):1-18. 5. Reich et al. Br J Dermatol. 2012;167(1):180-90. 6. Gladman et al. Arthritis Care Res (Hoboken). 2014;66(7):1085-92. 7. Sun. Application of Markov Chain Monte-Carlo Multiple Imputation Method to Deal with Missing Data from the Mechanism of MNAR in Sensitivity Analysis for a Longitudinal Clinical Trial. In: Chen et al. Monte-Carlo Simulation-Based Statistical Modeling. Singapore: Springer; 2017:233-52. Acknowledgements This study and all costs associated with the development of this poster were funded by Dermira, Inc. Dermira and UCB are in a strategic collaboration to evaluate the efficacy and safety of certolizumab pegol in the treatment of moderate-to- severe plaque psoriasis. Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL). Author Disclosures KR: Speaker’s fees, honoraria, and/or advisory board: AbbVie; Amgen; Biogen; Boehringer Ingelheim Pharma; Celgene; Centocor; Covagen; Forward Pharma; GlaxoSmithKline; Janssen-Cilag; LEO Pharma; Eli Lilly; Medac; Merck Sharp & Dohme; Novartis; Ocean Pharma; Pfizer; Regeneron; Takeda; UCB Pharma; Xenoport. AB: Consulting honoraria, clinical investigator, and/or speaker’s fees: AbbVie; Amgen; Boehringer Ingelheim Pharma; Celgene; Dermira, Inc.; Genentech; GlaxoSmithKline; Janssen; Eli Lilly; Merck; Novartis; Pfizer; Regeneron; Sandoz; Sanofi Genzyme; Sun Pharma; UCB Pharma; Valeant. DT: Consultant for: AbbVie, Biogen-Idec, Celgene, Dignity, Galapagos, Maruho, Mitsubishi, Novartis, Pfizer and Xenoport. Scientific Advisory Board: AbbVie, Amgen, Biogen-Idec, Celgene, Eli-Lilly, GlaxoSmithKline, LEO Pharma, Pfizer, Novartis, Janssen, Mundipharma; Sandoz. CL: Speaker’s fees, honoraria, and/or advisory board: AbbVie; Actavis; Amgen; Boehringer Ingelheim Pharma; Celgene; Coherus; Corrona; Dermira, Inc.; Eli Lilly; Galderma; Glenmark; Janssen; LEO Pharma; Merck; Novartis; Pfizer; Sandoz; Stiefel; UCB Pharma; Vitae; Wyeth. YP: Investigator (research grants): AbbVie; Baxter; Boehringer Ingelheim Pharma; Celgene; Centocor/Janssen; Eli Lilly; EMD Serono; GlaxoSmithKline; LEO Pharma; MedImmune; Merck; Novartis; Pfizer; Regeneron; Takeda; UCB Pharma. Speaker (honoraria): AbbVie; Celgene; Janssen; Eli Lilly; LEO Pharma; Novartis; Regeneron Sanofi Genzyme. Associate Editor of the Journal of Cutaneous Medicine and Surgery. DB, JD: Employees of Dermira, Inc. LP, CA: Employees of UCB Pharma. ABG: Consulting and/or Advisory Board Agreements: Abbvie, Aclaris, Amicus, Allergan, Behring, Beiersdorf, Inc., Bristol Myers Squibb Co., Celgene Corp., CSL Merck, Dermira, Development Crescendo Bioscience, Incyte, Janssen Inc., Lilly, Novartis, Pfizer, UCB, Reddy Labs, Sun Pharmaceutical Industries, Valeant, Xenoport. Research/Educational Grants (paid to Tufts Medical Center): Janssen Incyte. FC17PosterDermiraReichMaintenanceofResponse48wks.pdf