Presented at Fall Clinical Dermatology Conference 2019 | Las Vegas, NV, USA | 17–20 October, 2019 Previously Presented at the 6th Congress of the Skin Inflammation & Psoriasis International Network BACKGROUND • Plaque psoriasis (PSO) is an immune-mediated, inflammatory disease that affects around 3% of adults in the United States.1,2 • The Fc-free, PEGylated, anti-tumor necrosis factor (TNF) biologic certolizumab pegol (CZP) was approved by the FDA for moderate to severe PSO in 2018,3 and has shown a safety profile consistent with the anti-TNF class in adults with PSO over 48 weeks in phase 3 trials.4,5 • Here, we report cumulative safety data over 96 weeks from the CZP in PSO phase 3 clinical development program. METHODS Patients and Study Design • Safety data, pooled across studies, are presented for patients who received ≥1 dose of CZP during the first 96 weeks of the CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272), and CIMPACT (NCT02346240) phase 3 studies (Figure 1). • Only 11 placebo-randomized patients continued on placebo after Week 16; placebo data are presented to Week 16 only. • Patient inclusion criteria: ≥18 years of age, moderate to severe PSO ≥6 months with Psoriasis Area Severity Index (PASI) ≥12, ≥10% body surface area (BSA) affected, Physician’s Global Assessment (PGA) ≥3 on a 5-point scale; candidates for systemic PSO therapy, phototherapy, and/or photochemotherapy. • Exclusion criteria: previous treatment with CZP or >2 biologics; previous treatment with etanercept (ETN) (CIMPACT only); treatment with ETN within the first 12-weeks of enrolment (CIMPASI-1 and CIMPASI-2 only); history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized PSO types; current or history of chronic or recurrent viral, bacterial or fungal infections. Safety Assessments • Adverse events (AEs) and serious adverse events (SAEs) were classified using MedDRA version 18.1. • An SAE was defined as an AE meeting one or more of the following criteria: leading to death, life-threatening, leading to significant or persistent disability/incapacity, congenital anomalies/birth defects, an important medical event (based upon medical judgement) or leading to initial or prolonged inpatient hospitalization. • Incidence rates (IR) were calculated as incidence of new cases per 100 patient-years (PY). RESULTS Patient Population • Across all 3 studies, 995 patients received ≥1 dose CZP through Weeks 0–96. • Total exposure to CZP was 1,471 PY. • Baseline characteristics were well-balanced between treatment groups (Table 1). Incidence of AEs and SAEs • At Week 16, the IR of AEs within both the CZP 400 mg every two weeks (Q2W) and CZP 200 mg Q2W dose groups was comparable to that of placebo (Table 2). References 1. Kurd SK and Gelfand JM. JAAD 2009;60:218–24; 2. Rachakonda TD. et al. 2014;70:512–6; 3. Certolizumab Pegol Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125160s270lbl. pdf [Last accessed: May 2019]; 4. Gottlieb AB. et al. JAAD 2018;79:302–14.e6; 5. Lebwohl M. et al. JAAD 2018;79:266–76.e5. Author Contributions Substantial contributions to study conception/design, or acquisition/ analysis/interpretation of data: AB, BS, RL, SK, CA, MB, ML, KR; Drafting of the publication, or revising it critically for important intellectual content: AB, BS, RL, SK, CA, MB, ML, KR; Final approval of the publication: AB, BS, RL, SK, CA, MB, ML, KR. Author Disclosures AB: Consulting honoraria and clinical investigator: AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira Inc., Eli Lilly, Galderma, Genentech/ Roche, GSK, Janssen, LEO Pharma, Meiji, Merck, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, Vidac. Speaker’s fees: Eli Lilly, Janssen, Regeneron, Sanofi Genzyme; BS: Consulting fees and/or other honoraria: AbbVie, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Dermira Inc., Janssen, Eli Lilly, LEO Pharma, Medac, Menlo Therapeutics, Novartis, Pfizer, GSK, UCB Pharma, Sun Pharma, Ortho Dermatologics/ Valeant, Regeneron, Sanofi Genzyme; CORRONA Psoriasis Registry; Grant Support to the University of Connecticut for Fellowship Program (payments to the University of Connecticut, not BS): AbbVie, Janssen; RL: Consulting fees and/or other honoraria: AbbVie, Amgen, Boehringer Ingelheim International GmbH, Centocor, Pfizer, Janssen, LEO Pharma, Eli Lilly, Valeant; SK, CA, MB: Employees of UCB Pharma; ML: Consultant for Allergan, Aqua, LEO Pharma, Promius. Employee of Mount Sinai which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/ Astra Zeneca, Novartis, Pfizer, Valeant, Vidac; KR: Advisor and/or paid speaker and/or clinicall investigator for AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GSK, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Takeda, UCB Pharma, Valeant, Xenoport. Acknowledgements The studies were funded by Dermira Inc. in collaboration with UCB Pharma. UCB is the regulatory sponsor of certolizumab pegol in psoriasis. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. The authors acknowledge Bartosz Łukowski, MSc, UCB Pharma, Brussels, Belgium for publication coordination and Amelia Frizell-Armitage, PhD, Costello Medical, Cambridge, UK, for medical writing and editorial assistance. All costs associated with development of this poster were funded by UCB Pharma. Since conducting this work KR has moved institute and is now affiliated with Skinflammation® Center, Hamburg, and Dermatologikum Berlin, Berlin, Germany. CONCLUSIONS • The overall incidence of AEs and SAEs of interest was low and the IR of SAEs was comparable between the two dose groups. • Risk did not increase with longer exposure. • No new safety signals were identified compared with previous studies in CZP. • The safety profile of CZP dosed at both 400 mg and 200 mg Q2W was consistent with the anti-TNF class in PSO. OBJECTIVE • To report cumulative 96-week safety data from three phase 3 trials of certolizumab pegol in plaque psoriasis. Safety of Certolizumab Pegol in Plaque Psoriasis: Pooled 96-Week Data from Three Phase 3, Multicenter, Randomized, Placebo-Controlled Studies (CIMPASI-1, CIMPASI-2 and CIMPACT) A. Blauvelt,1 B. Strober,2,3 R. Langley,4 S. Kavanagh,5 C. Arendt,6 M. Boehnlein,7 M. Lebwohl,8 K. Reich9 1Oregon Medical Research Center, Portland, OR, USA; 2University of Connecticut Health Center, Farmington, CT, USA; 3Probity Medical Research, Waterloo, Ontario, Canada; 4Dalhousie University, Nova Scotia, Canada; 5UCB Pharma, Raleigh, NC, USA; 6UCB Pharma, Brussels, Belgium; 7UCB Pharma, Monheim, Germany; 8Icahn School of Medicine at Mount Sinai, New York, NY, USA; 9SCIderm Research Institute, Hamburg, and Dermatologikum Berlin, Germany Figure 1. CIMPASI-1, CIMPASI-2 and CIMPACT study design • The IR of AEs did not increase over time to Week 96 for patients receiving CZP (Table 2). • At Week 96, the IR of SAEs was comparable between the two CZP dose groups (Table 3). Selected AEs and SAEs of Interest • At Week 96, the overall incidence of selected AEs and SAEs of interest was low (Table 3). • There were 4 deaths, 1 of which in the CZP 200 mg Q2W dose group was assessed by the Investigator as related to the study drug (Table 3). • There were no reports of serious skin disorders such as Steven Johnson or Lupus. aLoading dose of CZP 400 mg Q2W at Weeks 0, 2 and 4 or Weeks 16, 18 and 20; bDepending on PASI response, any dose adjustments were either mandatory or at the discretion of the Investigator. BW: twice per week; CZP: certolizumab pegol; ETN: etanercept; LD: loading dose; PASI: Psoriasis Area Severity Index; Q2W: every two weeks; Q4W: every four weeks. Table 1. Pooled demographics and baseline characteristics for patients who received ≥1 dose CZP through Weeks 0–96 aPatients who received both CZP 200 mg Q2W and CZP 400 mg Q2W are only included once in the population count for the ‘All CZP’ group. BMI: body mass index; CZP: certolizumab pegol; IL: interleukin; PASI: Psoriasis Area Severity Index; Q2W: every two weeks; SD: standard deviation; TNF: tumor necrosis factor. Table 2. Cumulative AEs over time at Weeks 16, 48 and 96 aPatients who received both CZP 200 mg Q2W and CZP 400 mg Q2W are only included once in the population count for the ‘All CZP’ group. AE: adverse event; CI: confidence interval; CZP: certolizumab pegol; IR: incidence rate per 100 patient-years; Q2W: every two weeks. Table 3. Overview of AEs and SAEs to Week 96 aPatients who received both CZP 200 mg Q2W and CZP 400 mg Q2W are only included once in the population count for the ‘All CZP’ group; bOther commonly reported AEs (≥5% patients) included arthalgia, headache, psoriasis and hypertension; cTwo each of pneumonia, erysipelas, and one each of abdominal abscess, appendicitis, Escherichia sepsis, endophthalmitis, ovarian abscess, Klebsiella pneumonia, bronchitis, bacteraemia, sepsis, tuberculosis, pyelonephritis, haematoma infection; dTwo cellulitis events and one each of gastroenteritis, pancreas infection, Borrelia infection, Bartholin’s abscess, Varicella, infected bite, pneumonia, bronchitis, pyoderma, urinary tract infection; eOne each of adenocarcinoma of the colon, anaplastic oligodendroglioma, prostate cancer, clear cell renal cell carcinoma; fOne each of breast cancer, glioblastoma, Hodgkin’s disease, laryngeal cancer, prostate cancer; gTwo basal cell carcinoma, one keratoacanthoma; hOne craniocerebral injury and one multiple injuries, both assessed as unrelated to study drug; iOne chronic obstructive pulmonary disease assessed as unrelated to study drug, one patient experienced distributive shock, cardiac arrest, hepatic failure and disseminated intravascular coagulation and death was assessed as related to the study drug by the Investigator. AE: adverse event; CI: confidence interval; CZP: certolizumab pegol; IR: incidence rate; PY: patient-years; Q2W: every two weeks; SAE: serious adverse event; TNF: tumor necrosis factor. All CZPa (N=995) CZP 400 mg Q2W (N=711) CZP 200 mg Q2W (N=726) Patient and disease characteristics Age, years, mean ± SD 45.6 ± 13.2 45.7 ± 13.0 45.3 ± 13.1 Male, n (%) 652 (65.5) 463 (65.1) 487 (67.1) BMI, kg/m2, mean ± SD 30.4 ± 7.0 30.7 ± 7.2 30.2 ± 6.7 Disease duration, years, mean ± SD 18.2 ± 12.5 18.3 ± 12.4 18.5 ± 12.6 PASI, mean ± SD 20.2 ± 7.8 20.2 ± 7.7 20.2 ± 7.8 Prior treatment Biologic therapy, n (%) Anti-TNF Anti-IL-17 Anti-IL-12/IL-23 299 (30.1) 122 (12.3) 149 (15.0) 49 (4.9) 219 (30.8) 87 (12.2) 106 (14.9) 42 (5.9) 219 (30.2) 91 (12.5) 109 (15.0) 30 (4.1) Prior systemic therapy for psoriasis, n (%) 714 (71.8) 519 (73.0) 526 (72.5) n/N (%) IR (95% CI) All CZPa CZP 400 mg Q2W CZP 200 mg Q2W Placebo Week 16 414/692 (59.8) 319.1 (289.1, 351.4) 217/342 (63.5) 348.3 (303.5, 397.9) 197/350 (56.3) 292.1 (252.8, 335.9) 97/157 (61.8) 342.6 (277.8, 417.9) Week 48 709/962 (73.7) 219.6 (203.7, 236.4) 444/627 (70.8) 228.6 (207.8, 250.9) 321/460 (69.8) 221.2 (197.6, 246.7) - Week 96 820/995 (82.4) 172.7 (161.1, 184.9) 528/711 (74.3) 186.4 (170.9, 203.0) 514/726 (70.8) 161.4 (147.8, 176.0) - All CZPa (N=995) CZP 400 mg Q2W (N=711) CZP 200 mg Q2W (N=726) Exposure (PY) 1,471 700 772 Total AEs, IR (95% CI) Total SAEs, IR (95% CI) 172.7 (161.1, 184.9) 9.2 (7.7, 10.9) 186.4 (170.9, 203.0) 10.8 (8.5, 13.7) 161.4 (147.8, 176.0) 7.7 (5.9, 10.0) Most commonly reported AEs (≥10% patients),b IR (95% CI) Nasopharyngitis Upper respiratory tract infection 19.0 (16.6, 21.6) 10.3 (8.6, 12.2) 21.8 (18.3, 25.9) 11.9 (9.4, 14.9) 19.4 (16.2, 23.1) 9.6 (7.4, 12.1) Selected AEs and SAEs of interest, IR (95% CI) Serious infections Active tuberculosis Primary progressive multiple sclerosis Congestive heart failure Malignancies (excluding non-melanoma skin cancer) Non-melanoma skin cancer 1.7 (1.1, 2.5) 0.1 (0.0, 0.4) 0.1 (0.0, 0.4) 0.1 (0.0, 0.4) 0.5 (0.2, 1.1) 0.2 (0.0, 0.6) 1.7 (0.9, 3.0)c 0.1 (0.0, 0.8) 0.1 (0.0, 0.8) 0.1 (0.0, 0.8) 0.6 (0.2, 1.5)e 0.4 (0.1, 1.3)g 1.6 (0.8, 2.7)d 0.0 0.0 0.0 0.7 (0.2, 1.5)f 0.0 Discontinuations due to AEs, IR (95% CI) Severe AEs, IR (95% CI) AEs leading to death, IR (95% CI) 4.3 (3.3, 5.5) 7.4 (6.0, 9.0) 0.3 (0.1, 0.7) 5.5 (3.9, 7.5) 8.6 (6.5, 11.1) 0.3 (0.0, 1.0)h 3.4 (2.2, 5.0) 6.6 (4.8, 8.7) 0.3 (0.0, 0.9)i 0 16 484032Week Initial treatment period (double-blinded) LDa CZP 200 mg Q2W CZP 400 mg Q2W 14496 Open-label treatment Placebo Q2W LDa CZP 200 mg Q2W CZP 400 mg Q2W ≥PASI 50 Re-randomization Initial treatment period (double-blinded) Maintenance period (double-blinded)