POS0220 INTEGRATED SAFETY PROFILE OF UPADACITINIB WITH UP TO 4.5 YEARS OF EXPOSURE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: S. B. Cohen, R. Van Vollenhoven, J. R. Curtis, L. Calabrese, C. Zerbini, Y. Tanaka, L. Bessette, C. Richez, I. Lagunes-Galindo, J. Liu, H. Camp, Y. Song, S. Anyanwu, G. R. Burmester
Journal: Annals of the Rheumatic Diseases (2021)

Background: The safety and efficacy of the oral Janus kinase inhibitor upadacitinib (UPA) has been evaluated across a spectrum of patients with rheumatoid arthritis (RA) in the phase 3 SELECT clinical program. 1–6 Objectives: To describe the long-term integrated safety profile of UPA relative to active comparators (cutoff date: June 30, 2020) in patients with RA treated in the SELECT clinical program. Methods: This analysis included updated data from 6 randomized controlled UPA RA trials. 1–6 Treatment-emergent adverse events (TEAEs; onset after first dose and ≤30 days after last dose of study drug or ≤70 days for adalimumab [ADA]) including AEs of special interest were summarized as follows: pooled UPA 15 mg once daily (QD; UPA15, 6 trials); pooled UPA 30 mg QD (UPA30, 4 trials); methotrexate (MTX, 1 trial), and ADA (1 trial). TEAEs were reported as exposure-adjusted adverse event rates (EAERs; events/100 patient-years [E/100 PY]), which included both incident and recurrent events. Results: 4413 patients (UPA15, n=3209; UPA30, n=1204) received ≥1 dose of UPA, providing 10,115.4 PY of exposure. EAERs for AEs, serious AEs (SAEs), and AEs leading to discontinuation were similar for UPA15, MTX, and ADA; rates for UPA30 were numerically higher than UPA15 (Table 1). The most common AEs were upper respiratory tract infection, nasopharyngitis, and urinary tract infection for both UPA doses, and for UPA30 only, increased creatine phosphokinase (CPK). Pneumonia was the most common SAE for both UPA15 and UPA30. Serious infection rates were similar for UPA15, MTX, and ADA but higher for UPA30 (Figure 1). Rates of herpes zoster (HZ) were higher for both UPA groups (dose-dependent) vs MTX and ADA. Most HZ cases with UPA were non-serious (94%) and involved a single dermatome (74%). CPK elevations, which were mostly asymptomatic, were more common for both UPA groups (dose-dependent) vs MTX and ADA. EAERs of adjudicated gastrointestinal perforations were &lt;0.1 and 0.2 E/100 PY for UPA15 and UPA30, respectively. Rates of non-melanoma skin cancer (due in part to more recurrent events with UPA30), anemia, and neutropenia were higher with UPA30 vs other treatment groups. Events of anemia and neutropenia were generally mild/moderate and treatment discontinuation due to these events was uncommon (&lt;0.4%). Rates of other AEs of special interest, including major adverse cardiovascular and venous thromboembolic events, were broadly similar across treatment groups. The rate of deaths in UPA-treated patients with RA was not higher than expected for the general population (standardized mortality ratio [95% confidence interval (CI)]: UPA15, 0.43 [0.29, 0.63]; UPA30, 0.68 [0.40, 1.08]). Table 1. TEAEs in patients treated with UPA, MTX, and ADA UPA 15 mg QD UPA 30 mg QD ADA 40 mg EOW MTX n 3209 1204 579 314 Exposure Total, PY 7023.8 3091.6 1051.8 637.4 Mean (SD), weeks 114 (64) 134 (66) 95 (70) 106 (67) Median (range), weeks 136 (0, 232) 160 (0, 231) 118 (2, 231) 144 (1, 221) E/100 PY (95% CI ) Any AE 230.7 (227.2, 234.3) 283.6 (277.7, 289.6) 216.6 (207.8, 225.7) 227.8 (216.2, 239.8) Any SAE 13.0 (12.2, 13.9) 18.8 (17.3, 20.4) 13.3 (11.2, 15.7) 10.4 (8.0, 13.2) Any AE leading to discontinuation of study drug 5.6 (5.0, 6.1) 8.5 (7.5, 9.6) 6.8 (5.3, 8.5) 6.3 (4.5, 8.5) Deaths a 0.4 (0.3, 0.6) 0.6 (0.3, 0.9) 0.9 (0.4, 1.6) 0.5 (0.1, 1.4) a Both treatment and non-treatment-emergent deaths EOW, every other week Conclusion: The updated safety profile of UPA with up to 4.5 years of exposure in patients with RA was comparable to previous analyses, 7 with no new safety signals reported. With the exception of HZ and elevated CPK, the safety profile of UPA15, the approved dose for RA, was similar to that observed for ADA. References: [1]Burmester GR, et al. Lancet 2018;391:2503–12; [2]Smolen JS, et al. Lancet 2019;393:2303–11; [3]Fleischmann R, et al. Arthritis Rheumatol 2019;71:1788–800; [4]Genovese MC, et al. Lancet 2018;391:2513–24; [5]van Vollenhoven R, et al. Arthritis Rheumatol 2020;72:1607–20; [6]Rubbert-Roth A, et al. N Engl J Med 2020;383:1511–21; [7]Cohen SB, et al. Ann Rheum Dis 2020;79(Suppl 1):319–20. Acknowledgements: AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests: Stanley B. Cohen Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Gilead, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Gilead, Pfizer, Roche, and Sandoz, Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Medac, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, Eli Lilly, GSK, Pfizer, and UCB, Jeffrey R. Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Crescendo, Janssen, Pfizer, Sanofi/Regeneron, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Crescendo, Janssen, Pfizer, Sanofi/Regeneron, and UCB, Leonard Calabrese Speakers bureau: AbbVie, Crescendo, Genentech, Horizon, Janssen, Novartis, and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GSK, Horizon, Janssen, Novartis, and Sanofi, Cristiano Zerbini Speakers bureau: MSD, Pfizer, and Sanofi, Consultant of: MSD, Pfizer, and Sanofi, Grant/research support from: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, and Servier, Yoshiya Tanaka Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, GSK, Janssen, Mitsubishi Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics, Grant/research support from: Asahi Kasei, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Takeda, and UCB, Louis Bessette Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Christophe Richez Speakers bureau: AbbVie, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, GSK, MSD, and Pfizer, Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, GSK, MSD, and Pfizer, Ivan Lagunes-Galindo Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, Roche, and UCB, Consultant of: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, Roche, and UCB