OP0061 DEVELOPMENT OF EXTRA-MUSCULOSKELETAL MANIFESTATIONS IN UPADACITINIB-TREATED PATIENTS WITH PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS, OR NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; pp. 40 - 41
• Main Authors: Poddubnyy, D, Parikh, B, Elewaut, D, Navarro-Compán, V, Siebert, S, Paley, M, Coombs, D, Mccaskill, R, Biljan, A, Wung, P, Lubrano, E
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2023
• Subjects: Adverse events; Ankylosing spondylitis; Clinical trials; Data collection; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory diseases; Intestine; Patients; Psoriasis; Psoriatic arthritis; Rheumatic diseases; Stockholders; Uveitis
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.2394

BackgroundExtra-musculoskeletal manifestations (EMMs) are common in patients with spondyloarthritis (SpA), but there are limited data on the impact of upadacitinib (UPA), an oral JAK inhibitor, on EMMs in SpA patients.ObjectivesTo assess the development of EMMs among patients with PsA, AS, or non-radiographic axial spondyloarthritis (nr-axSpA) treated with UPA 15 mg (UPA15) or placebo (PBO) in the SELECT clinical trial program.MethodsThis analysis includes safety data from UPA trials in PsA (2 trials),[1,2] AS (2 trials),[3,4] and nr-axSpA (1 trial).[5] All trials were designed with initial randomization to UPA or PBO for a pre-specified number of weeks, followed by a second open-label extension where PBO-treated patients were switched to UPA. Treatment-emergent adverse events (TEAEs) of EMMs, including uveitis, inflammatory bowel disease (IBD), and psoriasis, were assessed; as psoriasis is considered a core manifestation of PsA, it was only evaluated as an EMM in AS and nr-axSpA.[6] TEAEs were defined as an AE with onset on or after first dose of study drug and ≤30 days after last dose and summarized for PsA (pooled PBO to week 24 and pooled UPA15 to data cut-off [15 Aug 2022]), AS (pooled PBO to week 14 and pooled UPA15 to data cut-off), and nr-axSpA (PBO to week 52 and UPA15 to data cut-off). EMMs are reported as exposure-adjusted event rates (EAERs; events/100 patient years [E/100 PY]) and are stratified by patients with a reported history (flare) of the respective EMM vs those without a history (new onset).ResultsThe vast majority (92-99%) of patients across PsA, AS, and nr-axSpA did not have a prior history of EMMs at baseline (Table 1). In PsA, development of uveitis and IBD were low regardless of treatment or prior history (Figure 1). In AS, development of uveitis was numerically higher (E/100 PY [95% CI]) in patients treated with PBO (total: 7.5 [2.7, 16.3]) vs UPA15 (total: 2.8 [1.8, 4.1]) and in patients with a prior history of uveitis (PBO: 6.2 [2.0, 14.5], UPA15: 2.1 [1.3, 3.3]) vs no prior history (PBO: 1.2 [0.0, 6.9]; UPA15: 0.6 [0.2, 1.4]); occurrence of IBD and psoriasis were low regardless of treatment or prior history. In nr-axSpA, development of uveitis was low regardless of prior history, while the total rate was numerically higher in patients treated with PBO (2.1 [0.4, 6.3]) vs UPA15 (0.9 [0.2, 2.7]); occurrence of IBD and psoriasis were low or absent.ConclusionData from this post-hoc analysis describe adverse events of relevant EMMs in the SELECT program and should be interpretated with caution as the efficacy of UPA in patients with specific EMMs was not systematically evaluated, as well as the overall low number of events observed. Development of EMMs in patients treated with UPA15 was generally low across PsA, AS, and nr-axSpA. Uveitis was numerically higher in patients treated with PBO vs UPA, and particularly in patients with AS. A better understanding of the impact of UPA across EMMs in SpA, and subsequent follow-up analyses, may help clinicians make informed treatment decisions and guide future treatment recommendations.References[1]McInnes et al. N Eng J Med. 2021;384(13):1227-39.[2]Mease et al. Ann Rheum Dis. 2021;80(3):312-20.[3]van der Heijde et al. Lancet. 2019;394(10214):2108-17.[4]van der Heijde et al. Ann Rheum Dis. 2022;81(11):1515-23.[5]Deodhar et al. Lancet. 2022;400(10349):369-79.[6]Coates et al. Nat Rev Rheumatol. 2022;18(8):465-479.Table 1.Prior History of EMMs Reported at Baseline in Patients Treated With UPA Across PsA, AS, and nr-axSpAPsAASnr-axSpAEMM, n (%)PBO n=635UPA 15 mg QDa n=907PBO n=303UPA 15 mg QDa n=596PBO n=157UPA 15 mg QDa n=286Uveitis5 (0.8)8 (0.9)23 (7.6)49 (8.2)11 (7.0)21 (7.3)Inflammatory bowel disease10 (1.6)13 (1.4)7 (2.3)16 (2.7)6 (3.8)8 (2.8)PsoriasisN/AbN/Ab10 (3.3)19 (3.2)4 (2.5)7 (2.4)N/A, not applicable; QD, once daily; UPA.aAny UPA exposure, including patients who switched from PBO to UPA.bAs psoriasis is considered a core manifestation of PsA, it was only evaluated as an EMM in AS and nr-axSpA.AcknowledgementsAbbVie funded these studies (NCT03104400, NCT03104374, NCT03178487, NCT04169373) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsDenis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer, Bhumik Parikh Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Dirk Elewaut Speakers bureau: AbbVie, Consultant of: AbbVie, Victoria Navarro-Compán Speakers bureau: AbbVie, BMS, Galapagos, Janssen, Lilly, MoonLake, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, BMS, Galapagos, Janssen, Lilly, MoonLake, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, BMS, Galapagos, Janssen, Lilly, MoonLake, MSD, Novartis, Pfizer, Roche, and UCB, Stefan Siebert Speakers bureau: AbbVie, Amgen, Eli Lilly, GSK, Janssen, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, GSK, Janssen, and UCB, Grant/research support from: Amgen, Boehringer-Ingelheim, BMS, Eli Lilly, GSK, Janssen and UCB, Michael Paley Consultant of: AbbVie and Priovant Therapeutics, Grant/research support from: Lilly, Derek Coombs Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Reva McCaskill Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Ana Biljan Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Ennio Lubrano Speakers bureau: AbbVie, Celgene, Galapagos, Janssen, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Celgene, Galapagos, Janssen, MSD, Novartis, and Pfizer, Grant/research support from: AbbVie, Celgene, Galapagos, Janssen, MSD, Novartis, and Pfizer.