AB0522 SAFETY PROFILE OF UPADACITINIB UP TO 3 YEARS IN PATIENTS WITH PSORIATIC ARTHRITIS: AN INTEGRATED ANALYSIS FROM THE PHASE 3 PROGRAM
Authors: G. R. Burmester, K. Winthrop, R. Blanco, P. Nash, P. Goupille, V. F. Azevedo, C. Salvarani, A. Rubbert-Roth, E. Lesser, R. Mccaskill, J. Liu, B. Pierre-Louis, S. Walko, R. Lippe, A. Lertratanakul, E. Ruderman
Journal: Annals of the Rheumatic Diseases (2021)

Background: The efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, in patients (pts) with active psoriatic arthritis (PsA) were demonstrated through 24 weeks in the phase 3 SELECT-PsA 1 and SELECT-PsA 2 placebo-controlled clinical trials. 1,2 Objectives: To describe the long-term integrated safety profile of UPA relative to adalimumab (ADA) in pts with PsA treated in the SELECT program. Methods: The SELECT-PsA program enrolled pts with prior inadequate response or intolerance to ≥1 non-biologic DMARD (SELECT-PsA 1) or ≥1 biologic DMARD (SELECT-PsA 2). Both trials include UPA 15 mg and 30 mg, and only SELECT-PsA 1 includes long-term comparison with ADA 40 mg every other week. Treatment-emergent adverse events (TEAEs: AE onset ≥first dose and ≤30 days after last dose for UPA and ≤70 days for ADA) were summarized for the following: pooled UPA 15; pooled UPA 30; and ADA. TEAEs are reported as exposure-adjusted event rates (EAERs; events/100 pts years [E/100 PY]) up to a cut-off date of 20 June 2020. Results: 2257 pts received ≥1 dose of UPA 15 (N=907; 1247.2 PYs), UPA 30 (N=921; 1257.4 PYs), or ADA (N=429; 549.7 PYs), with median (max) exposures of 69 (155), 69 (154), and 68 (152) weeks, respectively. EAERs of TEAEs and serious AEs were generally similar between UPA 15 and ADA and higher with UPA 30; rates of AEs leading to study drug discontinuation were generally similar across all groups (Table 1). Similarly, rates of serious infection were comparable between UPA 15 and ADA and higher with UPA 30 (Figure 1 next page). The most common serious infection was pneumonia. Rates of herpes zoster were lower with UPA 15 than UPA 30 but higher than ADA. Most herpes zoster events involved a single dermatome; no events involved the central nervous system or other internal organs. Lower rates of opportunistic infections (OI) excluding tuberculosis were observed with UPA 15 vs UPA 30; the most common OI was mucosal candida infection. Malignancies were reported at similar rates across all treatment groups; no events of lymphoma were reported. Age-gender-adjusted standardized incidence ratios for malignancies excluding NMSC indicated no increased risk with UPA compared to the general population. Rates of adjudicated major adverse cardiovascular events and venous thromboembolic events were ≤0.3 E/100 PY for both UPA arms; all pts had ≥1 risk factor. One adjudicated gastrointestinal perforation was reported with UPA 15. Table 1. Overall Treatment-emergent AEs for Upadacitinib and Adalimumab (E/100 PY [95% CI]) UPA 15 mg QD N=907 (1247.2 PY ) UPA 30 mg QD N=921 (1257.4 PY ) ADA 40 mg EOW N=429 (549.7 PY ) AEs 263.9 (254.9, 272.9) 321.5 (311.6, 331.5) 286.5 (272.4, 300.7) Serious AEs 10.3 (8.6, 12.1) 13.2 (11.2, 15.2) 9.6 (7.0, 12.2) AE leading to discontinuation 6.7 (5.2, 8.1) 7.8 (6.2, 9.3) 7.8 (5.5, 10.2) Deaths a 0.2 (-0.1, 0.4) 0.2 (-0.0, 0.5) 0.2 (-0.2, 0.5) a Deaths included non-treatment emergent deaths: UPA 15, 1; UPA 30, 1. ADA, adalimumab; AE, adverse event; CI, confidence interval; E, event; EOW, every other week; PY, patient years; QD, once daily; UPA, upadacitinib. Hepatic disorders were mostly transient, non-serious transaminase increases. Creatine phosphokinase elevations were reported more frequently with UPA 30 vs UPA 15; most were asymptomatic with no rhabdomyolysis reported. AEs of anemia, neutropenia, and lymphopenia were generally mild or moderate, non-serious. Except for rates of lymphopenia (higher with UPA 15), hepatic disorders, and neutropenia (both higher with ADA), lab-related TEAEs occurred at generally consistent rates between UPA 15 and ADA. Study drug discontinuation due to lab-related TEAEs was uncommon. Conclusion: The safety profiles of UPA 15 and ADA were generally similar; the rates of most AEs were higher with UPA 30 compared with ADA. Through the cut-off date, the safety profile of UPA 15 and UPA 30 in PsA pts demonstrated consistent results compared to what has been observed with UPA in rheumatoid arthritis. 3 References: [1]McInnes IB et al. Ann Rheum Dis , 2020; 79:12. [2]Mease PJ et al. Ann Rheum Dis , 2020. [3]Cohen SB et al. Ann Rheum Dis , 2020. Figure 1 Acknowledgements: AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis &amp; interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc. Disclosure of Interests: Gerd Rüdiger Burmester Speakers bureau: AbbVie, Gilead, Lilly, Pfizer, Consultant of: AbbVie, Gilead, Lilly, Pfizer, Kevin Winthrop Consultant of: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Grant/research support from: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Ricardo Blanco Consultant of: Abbvie, Lilly, Novartis, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Grant/research support from: Abbvie, MSD and Roche, Peter Nash Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Philippe Goupille Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Valderilio F Azevedo Consultant of: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Grant/research support from: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Carlo Salvarani Consultant of: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Grant/research support from: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Andrea Rubbert-Roth Consultant of: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Grant/research support from: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: AbbVie, Employee of: AbbVie, Bosny Pierre-Louis Shareholder of: AbbVie, Employee of: AbbVie, Sandra Walko Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.