P178 Long-term safety of upadacitinib across rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis encompassing ∼17,000 patient-years of clinical trial data

Abstract Background/Aims The SELECT clinical program aims to evaluate the long-term integrated safety profile of upadacitinib 15mg (UPA15) across rheumatological indications, in the context of active comparators. Methods Safety data (cutoff: 15/08/2024) from 11 phase 3 upadacitinib clinical trials were compiled for RA (6), PsA (2), AS (2; one phase 2/3), and nr-axSpA (1) for this integrated analysis. Treatment-emergent adverse events (TEAEs)(adverse events AEs onset on/after the first dose of drug and ≤30 days UPA15 and MTX or ≤ 70 days ADA after the last dose) are presented as exposure-adjusted event rates (EAERs; events/100 patient-years E/100 PY with 95% CIs). A subset of special interest TEAEs are also presented as exposure-adjusted incidence rates (EAIRs; n/100 PY) with 95% CIs. Deaths (including COVID-19), MACE, VTE, and gastrointestinal perforations were adjudicated by blinded, independent committees. Results 4998 patients (RA, n = 3209; PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received UPA15(16,683.5 PYs of exposure), with 12,000 PYs of exposure from RA studies. The rate of AEs leading to drug discontinuation was generally similar across treatment groups and indications (range: 4.1 to 5.8 E/100 PY). The most frequently reported AEs leading to UPA15 discontinuation varied by indication; RA: pneumonia (n = 22/575; 0.2 E/100 PY), PsA: COVID-19 (n = 7/151; 0.2 E/100 PY), AS: headache (n = 3/42; 0.3 E/100 PY), nr-axSpA: worsening axial spondyloarthritis, pulmonary embolism, and nasal polyps (each n = 2/20; 0.5 E/100 PY), and pooled axSpA: headache and pulmonary embolism (each n = 4/62; 0.3 E/100 PY). Serious and opportunistic infection rates were generally similar across treatment groups and indications, except for serious infection in PsA (predominately COVID-19/COVID-19 pneumonia), which was higher with UPA15 than ADA. The most common serious infection and serious AE with UPA15 across all indications was COVID-19 pneumonia. Herpes zoster rates were higher with UPA15 versus active comparators in RA (ADA and MTX) and PsA (ADA). Herpes zoster rates with UPA15 were similar across indications. Rates of malignancy excluding nonmelanoma skin cancer (NMSC) were generally similar across treatment groups and indications. Rates of NMSC were generally low and were higher with UPA15 than active comparators in RA and PsA. MACE and VTE rates were generally similar across treatment groups and indications. Rates of extra-musculoskeletal manifestations were generally low across PsA, AS, nr-axSpA, and pooled axSpA. COVID-19/COVID-19 pneumonia was the most common cause of death across all indications. Conclusion Except for serious infection (in PsA, predominately COVID-19/COVID-19 pneumonia), herpes zoster, elevated CPK, and NMSC, reported TEAE rates were generally similar with UPA15 treatment and active comparators (ADA and MTX) in RA and PsA. As reported previously, across RA, PsA, AS, nr-axSpA, and pooled axSpA, UPA15 demonstrated a consistent safety profile, with no new safety risks identified with long-term treatment. Real-world data are needed to further contextualize and confirm findings. Disclosure G.R. Burmester: Consultancies; Has received speaking or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Roche, and UCB. Honoraria; Has received speaking or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Roche and UCB. S.B. Cohen: Consultancies; Has received consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Gilead, Pfizer, Roche, and Sandoz. Grants/research support; Has received research grants from AbbVie, Amgen, Boehringer Ingelheim, Gilead, Pfizer, Roche, and Sandoz. A. Deodhar: Consultancies; Has received consultancy fees from Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Janssen and MoonLake. Honoraria; Has received speaker fees from Novartis and Pfizer. Grants/research support; Has received research grants from Novartis, Pfizer, AbbVie, Eli Lilly, and UCB Pharma. Other; Has received other support (medical writing support) from Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Janssen and MoonLake. E. Mysler: Consultancies; Has received consultancy fees from AbbVie, Alpine Immunology, AstraZeneca, BMS, Eli Lilly, GSK, Hi Bio, Janssen, Novartis, Pfizer, Roche, and Sandoz. Grants/research support; Has received grants/research support from AbbVie, Alpine Immunology, AstraZeneca, BMS, Eli Lilly, GSK, Hi Bio, Janssen, Novartis, Pfizer, Roche, and Sandoz. A. Rubbert-Roth: Consultancies; Has received consultancy fees from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. Honoraria; Has received honoraria for lectures from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. Y. Tanaka: Honoraria; Has received speaking fees and/or honoraria from AbbVie, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics. Grants/research support; Has received research grants from AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda. K.L. Winthrop: Consultancies; Has received consultancy fees from AbbVie, Bristol- Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB Pharma. Grants/research support; Has received research grants from AbbVie, Bristol- Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB Pharma. A. Gara: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. D. Coombs: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. I. Lagunes: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. L. Larbi: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. S. Meerwein: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. T. Shaw: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. C. Hansell: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. J. Curtis: Consultancies; Has received consultancy fees from AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, Janssen, Labcorp, Lilly, Novartis, Pfizer, Sanofi/Regeneron, and UCB. Grants/research support; Has received research grants from AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, Janssen, Labcorp, Lilly, Novartis, Pfizer, Sanofi/Regeneron, and UCB.