Presented at the 5th Annual 2020 PA & NP Fall Clinical Dermatology Conference, Orlando, Florida, November 13–15, 2020 Previously presented at Winter Clinical Dermatology Conference, Hawaii, 2020 Long-Term Safety of Certolizumab Pegol in Plaque Psoriasis: Pooled Analysis over 3 Years from Three Phase 3, Randomized, Placebo-Controlled Studies A. Blauvelt,1 C. Paul,2 P. van de Kerkhof,3 R. B. Warren,4 A. B. Gottlieb,5 R. G. Langley,6 F. Brock,7 C. Arendt,8 M. Boehnlein,9 M. Lebwohl,5 K. Reich10,11 1Oregon Medical Research Center, Portland, OR, USA; 2Paul Sabatier University, Toulouse, France; 3Radboud University, Nijmegen, The Netherlands; 4Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, UK; 5Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6Dalhousie University, Nova Scotia, Canada; 7UCB Pharma, Slough, UK; 8UCB Pharma, Brussels, Belgium; 9UCB Pharma, Monheim am Rhein, Germany; 10Centre for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Germany; 11Skinflammation® Center, Hamburg, Germany References 1. Certolizumab Pegol Prescribing Information. Available at www.accessdata.fda.gov/scripts/cder/daf/index. cfm; 2. Certolizumab Pegol Summary of Product Characteristics. Available at www.ema.europa.eu/en/ medicines/human/EPAR/cimzia-0; 3. Blauvelt A et al. JEADV 2019;33(suppl 3):21–2; 4. Gisondi P et al. Int J Mol Sci 2017;18:2427. Author Contributions Substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: AB, CP, PvdK, RBW, ABG, RGL, FB, CA, MB, ML, KR; Drafting of the publication, or revising it critically for important intellectual content: AB, CP, PvdK, RBW, ABG, RGL, FB, CA, MB, ML, KR; Final approval of the publication: AB, CP, PvdK, RBW, ABG, RGL, FB, CA, MB, ML, KR. Author Disclosures AB: AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira Inc., Eli Lilly, FLX Bio, Forte, Galderma, Janssen, LEO Pharma, Novartis, Ortho, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, UCB Pharma; CP: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira Inc., Eli Lilly, GSK, Janssen, LEO Pharma, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, UCB Pharma; PvdK: AbbVie, Almirall, Amgen, Bristol-Myers Squibb, Celgene, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis; RBW: AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Avillion, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, UCB Pharma, Xenoport; ABG: AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira Inc., Dr. Reddy’s Laboratories, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Sun Pharma, UCB Pharma, Valeant, XBiotech (no personal compensation); RGL: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, UCB Pharma, Valeant; FB, CA, MB: Employees of UCB Pharma; ML: Allergan, Aqua, LEO Pharma, Promius; Employee of Mount Sinai which received funds from: Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, Valeant, Vidac; KR: AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GSK, Janssen- Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly, Medac, Merck Sharp & Dohme, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Takeda, UCB Pharma, Valeant, Xenoport. Acknowledgments 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 these studies. The authors acknowledge Susanne Wiegratz, UCB Pharma, Monheim am Rhein, Germany for publication coordination, Sarah Kavanagh, MPH, of UCB Pharma, Raleigh, NC, USA for statistical analysis, and Joe Dixon, PhD, Costello Medical, Cambridge, UK for medical writing and editorial assistance. All costs associated with development of this poster were funded by UCB Pharma. Richard Warren is supported by the Manchester NIHR Biomedical Research Centre. OBJECTIVE • To report cumulative three-year safety data from three phase 3 trials of certolizumab pegol in plaque psoriasis. BACKGROUND • Certolizumab pegol (CZP) is an Fc-free, PEGylated, anti-tumor necrosis factor (TNF) biologic, which has been approved by the FDA and EMA for moderate to severe plaque psoriasis (PSO).1,2 • CZP has shown a safety profile consistent with the anti-TNF class in adults with PSO over 96 weeks in phase 3 trials.3 • Given that PSO is a chronic disease that can require management over much of a patient’s lifetime, it is important to establish the long-term safety profile of treatments.4 • Here, we report cumulative safety data, pooled from three CZP in PSO phase 3 trials over 144 weeks, from a total of 995 patients. METHODS Patients and Study Design • Pooled safety data are presented for patients who received ≥1 dose of CZP during the 144 weeks of the CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272), or 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 with PSO for ≥6 months; – Psoriasis Area and 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; history of or current, chronic or recurrent viral, bacterial or fungal infections. Safety Assessments • Safety data were analyzed for the dose-combined CZP- treated group (All CZP) and separately for each CZP dose. • For patients exposed to both doses of CZP over the course of the studies, treatment-emergent adverse events (TEAEs) were assigned to the dose being received at the time of onset, but each patient was counted in the ‘All CZP’ group only once. • TEAEs and serious TEAEs were classified using MedDRA version 18.1. • Serious TEAEs were defined as those meeting one or more of the following criteria: life-threatening, leading to death, hospitalization, congenital anomalies/birth defects, medically significant (based upon medical judgement), infections requiring intravenous antibiotics, or leading to persistent or significant disability. • Incidence rates (IR) were calculated as the number of new cases per 100 patient-years (PY). CONCLUSIONS • No new safety signals were identified compared to previous studies in CZP. • The risk of TEAEs did not increase with longer or higher CZP exposure. • The safety profiles of the two CZP doses were similar. Figure 1. CIMPASI-1, CIMPASI-2, and CIMPACT study designs Dose adjustments were permitted during the open-label periods of all three studies, and were either mandatory or at the discretion of the investigator. Data collected during treatment with CZP 400 mg Q4W in CIMPACT were summarized under the CZP 200 mg Q2W treatment group. aLoading dose of CZP 400 mg Q2W at Weeks 0, 2 and 4 or Weeks 16, 18, and 20. 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. RESULTS Patient Population • Across all three studies, a total of 995 patients received ≥1 dose CZP through Weeks 0–144. • Baseline characteristics were well balanced between the two treatment groups (Table 1). Incidence of TEAEs • At Week 144, the IR of TEAEs and serious TEAEs was comparable between CZP dose groups (Table 2). • The most common TEAEs, reported in ≥10% of patients, were nasopharyngitis (IR: 14.2; 95% CI: 12.5, 16.0) and upper respiratory tract infection (IR: 7.9; 95% CI: 6.7, 9.3). • The IR of TEAEs for CZP-treated patients did not increase with longer exposure (Table 3). Selected TEAEs and Serious TEAEs of Interest • At Week 144 the overall incidences of selected TEAEs of interest and serious TEAEs of interest were low and comparable between dose groups (Table 4). • There were 7 deaths, 2 of which were assessed by the investigator as related to the study drug (Table 2). • The IRs of serious infections and malignancies were low, and were comparable between dose groups (Table 4). • There was 1 case of active tuberculosis (TB) in a patient who lived in a country with a high TB prevalence (Table 4). • There were no reports of serious skin disorders or hypersensitivity reactions, and no cases of lupus or lupus-like events. Table 1. Pooled demographics and baseline characteristics for patients who received ≥1 dose CZP through Weeks 0–144 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; bCZP 200 mg Q2W patients received a loading dose of CZP 400 mg at Weeks 0, 2, and 4 or Weeks 16, 18, and 20. BMI: body mass index; CZP: certolizumab pegol; IL: interleukin; PASI: Psoriasis Area Severity Index; PSO: psoriasis; Q2W: every two weeks; SD: standard deviation; TNF: tumor necrosis factor. All CZPa (N=995) CZP 400 mg Q2W (n=728) CZP 200 mg Q2Wb (n=731) Baseline demographics and disease characteristics Age, years, mean ± SD 45.6 ± 13.2 45.7 ± 13.1 45.3 ± 13.1 Male, n (%) 652 (65.5) 472 (64.8) 491 (67.2) BMI, kg/m2, mean ± SD 30.4 ± 7.0 30.6 ± 7.1 30.2 ± 6.7 PSO disease duration, years, mean ± SD 18.2 ± 12.5 18.2 ± 12.4 18.4 ± 12.6 PASI, mean ± SD 20.2 ± 7.8 20.2 ± 7.7 20.1 ± 7.8 Prior treatments Biologic therapy, n (%) 299 (30.1) 220 (30.2) 221 (30.2) Anti-TNF 123 (12.4) 88 (12.1) 94 (12.9) Anti-IL-17 149 (15.0) 106 (14.6) 109 (14.9) Anti-IL-12/IL-23 49 (4.9) 43 (5.9) 30 (4.1) Systemic therapy for PSO, n (%) 714 (71.8) 532 (73.1) 529 (72.4) Table 2. Overview of TEAEs in CZP-treated patients to Week 144 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; bCZP 200 mg Q2W patients received a loading dose of CZP 400 mg at Weeks 0, 2, and 4 or Weeks 16, 18, and 20; cOne case each of acute myocardial infarction, cardiac arrest (due to liver failure and vasodilatory shock in association with hemorrhagic pancreatic necrosis), pneumonia Legionella, cirrhosis alcoholic, chronic obstructive pulmonary disease, craniocerebral injury, and multiple injuries, the first two of which were considered related to the study drug by the investigator. CI: confidence interval; CZP: certolizumab pegol; IR: incidence rate; PY: patient-years; Q2W: every two weeks; TEAE: treatment-emergent adverse event. All CZPa (N=995) CZP 400 mg Q2W (n=728) CZP 200 mg Q2Wb (n=731) Total exposure, PY 2,231 1,020 1,211 n (%) IR (95% CI) n (%) IR (95% CI) n (%) IR (95% CI) Total TEAEs 847 (85.1) 144.9 (135.3, 155.0) 563 (77.3) 158.3 (145.5, 171.9) 557 (76.2) 134.1 (123.2, 145.7) Total Serious TEAEs 154 (15.5) 7.5 (6.4, 8.8) 82 (11.3) 8.7 (6.9, 10.8) 76 (10.4) 6.7 (5.2, 8.3) TEAEs leading to discontinuation 88 (8.8) 4.0 (3.2, 4.9) 48 (6.6) 4.7 (3.5, 6.3) 41 (5.6) 3.4 (2.5, 4.6) Severe TEAEs 132 (13.3) 6.3 (5.3, 7.5) 70 (9.6) 7.2 (5.6, 9.1) 66 (9.0) 5.7 (4.4, 7.2) TEAEs leading to death 7 (0.7)c 0.3 (0.1, 0.6) 3 (0.4) 0.3 (0.1, 0.9) 4 (0.5) 0.3 (0.1, 0.8) A) CIMPASI-1 and CIMPASI-2 B) CIMPACT Table 3. Cumulative TEAEs over time at Weeks 16, 48, 96, and 144 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; bCZP 200 mg Q2W patients received a loading dose of CZP 400 mg at Weeks 0, 2, and 4 or Weeks 16, 18, and 20. CI: confidence interval; CZP: certolizumab pegol; IR: incidence rate; PY: patient-years; Q2W: every two weeks; TEAE: treatment-emergent adverse event. All CZPa CZP 400 mg Q2W CZP 200 mg Q2Wb Placebo Week 16 Exposure, PY n/N (%) IR (95% CI) 211 414/692 (59.8) 319.1 (289.1, 351.4) 105 217/342 (63.5) 348.3 (303.5, 397.9) 107 197/350 (56.3) 292.1 (252.7, 335.9) 47 97/157 (61.8) 342.6 (277.8, 417.9) Week 48 Exposure, PY n/N (%) IR (95% CI) 729 709/962 (73.7) 219.6 (203.7, 236.4) 418 444/627 (70.8) 228.6 (207.8, 250.9) 311 321/460 (69.8) 221.2 (197.6, 246.7) – Week 96 Exposure, PY n/N (%) IR (95% CI) 1,471 820/995 (82.4) 172.7 (161.1, 184.9) 700 528/711 (74.3) 186.4 (170.9, 203.0) 772 514/726 (70.8) 161.4 (147.8, 176.0) – Week 144 Exposure, PY n/N (%) IR (95% CI) 2,231 847/995 (85.1) 144.9 (135.3, 155.0) 1,020 563/728 (77.3) 158.3 (145.5, 171.9) 1,211 557/731 (76.2) 134.1 (123.2, 145.7) – Table 4. Selected TEAEs and serious TEAEs of interest 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; bCZP 200 mg Q2W patients received a loading dose of CZP 400 mg at Weeks 0, 2, and 4 or Weeks 16, 18, and 20; cInclusive of fatal and non-fatal myocardial infarction, serious cerebrovascular events and congestive heart failure (regardless of seriousness); dPatient with negative QuantiFERON TB GOLD test and normal chest X-ray before study entry who was randomized to ETN, entered CZP 400 mg Q2W escape arm at Week 16, and was diagnosed 60 days after CZP initiation and discontinued the study; eOne case of primary progressive multiple sclerosis (medical history indicated that symptoms pre-dated study entry); fOne case of multiple sclerosis; gIncludes one each of heart failure, congestive heart failure, acute coronary syndrome and extradural hematoma; hIncludes one each of acute myocardial infarction, angina pectoris and cerebrovascular accident, and two transient ischemic attacks; iIncludes one each of adenocarcinoma of colon, anaplastic oligodendroglioma, prostate cancer and clear cell renal cell carcinoma; jIncludes one each of breast cancer, glioblastoma, Hodgkin’s disease, laryngeal cancer, non-small cell lung cancer, oropharyngeal squamous cell carcinoma and prostate cancer; kIncludes three basal cell carcinomas and one keratoacanthoma; lOne basal cell carcinoma. CI: confidence interval; CZP: certolizumab pegol; ETN: etanercept; IR: incidence rate; NMSC: non-melanoma skin cancer; PY: patient-years; Q2W: every two weeks; TB: tuberculosis; TEAE: treatment-emergent adverse event. All CZPa (N=995) CZP 400 mg Q2W (n=728) CZP 200 mg Q2Wb (n=731) Total exposure, PY 2,231 1,020 1,211 n (%) IR (95% CI) n (%) IR (95% CI) n (%) IR (95% CI) Serious infections 32 (3.2) 1.5 (1.0, 2.1) 16 (2.2) 1.6 (0.9, 2.6) 16 (2.2) 1.3 (0.8, 2.2) Active tuberculosis 1 (0.1) 0.0 (0.0, 0.3) 1 (0.1)d 0.1 (0.0, 0.6) 0 (0.0) 0 (0.0, 0.0) Demyelinating-like disorders 2 (0.2) 0.1 (0.0, 0.3) 1 (0.1)e 0.1 (0.0, 0.6) 1 (0.1)f 0.1 (0.0, 0.5) Major adverse cardiac events (MACE)c 9 (0.9) 0.4 (0.2, 0.8) 4 (0.5)g 0.4 (0.1, 1.0) 5 (0.7)h 0.4 (0.1, 1.0) Congestive heart failure 1 (0.1) 0.0 (0.0, 0.3) 1 (0.1) 0.1 (0.0, 0.6) 0 (0.0) 0 (0.0, 0.0) All malignancies 14 (1.4) 0.6 (0.3, 1.1) 8 (1.1) 0.8 (0.3, 1.6) 8 (1.1) 0.7 (0.3, 1.3) Malignancies excluding NMSC 10 (1.0) 0.5 (0.2, 0.8) 4 (0.5)i 0.4 (0.1, 1.0) 7 (1.0)j 0.6 (0.2, 1.2) NMSC 5 (0.5) 0.2 (0.1, 0.5) 4 (0.5)k 0.4 (0.1, 1.0) 1 (0.1)l 0.1 (0.0, 0.5) 0 16 484032Week Initial treatment period (double-blinded)