POS0231 COMPARATIVE SAFETY OF JAK INHIBITORS VERSUS TNF OR IL-17 INHIBITORS FOR CARDIOVASCULAR DISEASE, VENOUS THROMBOEMBOLISM AND CANCER IN PSORIATIC ARTHRITIS AND AXIAL SPONDYLOARTHRITIS
Authors: S. S. Zhao, D. Riley, P. Austin, G. Hernandez, U. Alam
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Compared to TNF inhibitors, tofacitinib was shown to increase risk of cardiovascular disease (CVD) and cancer among people with rheumatoid arthritis with risk of CVD. Although JAK inhibitors (JAKi) are widely used in spondyloarthritis (SpA), their safety profile remains unclear. Risk profiles may differ among SpA patients who are typically younger and have lower systemic inflammatory burden. <h3>Objectives:</h3> To compare, among people with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), the risk of CVD, venous thromboembolism (VTE) and common cancers between JAKi versus TNF or IL-17 inhibitors. <h3>Methods:</h3> We used data from TriNetX Global Collaborative Network, a federated research network for electronic medical records comprising &gt;100 healthcare organizations (mostly in the USA) and &gt;100 million patients. A population of adults (age ≥18 years) with SpA was defined using at least one ICD-10 code for axSpA (M45) or PsA (L40.5), excluding those with codes for rheumatoid (M05, M06) or juvenile idiopathic arthritis (M08). Patients were included if they initiated any drugs in each of three exposure groups, namely 1) JAKi (tofacitinib/upadacitinib), 2) any TNFi, 3) IL17i (secukinumab/ixekizumab). Drug initiation date was defined as the index date. Three composite outcomes were defined using incident ICD-10 codes: 1) CVD: acute myocardial infarction or cerebral infarction (I21, I63), 2) VTE: pulmonary embolism or deep vein thrombosis (I26, I80.1-3), 3) selected cancers: breast (C50), colorectal (C18-20), lung (C34), or prostate (C61). We additionally included a positive control outcome, herpes zoster (B02). Time to each outcome was compared using 1:1 propensity-score (PS) matched Cox proportional hazards models, using greedy nearest neighbour matching and calliper of 0.1. PS were derived using logistic regression of exposure group (JAKi vs TNFi then separately for JAKi vs IL-17i) against the following variables: age, gender, ethnicity (white vs non-white), BMI (&lt;25, 25-30, &gt;30kg/m<sup>2</sup>, missing), CRP (&lt;5, 5-10, &gt;10mg/dL, missing), axSpA/PsA, hypertension, tobacco use, COPD (as proxy for smoking), overweight/obesity, type 2 diabetes mellitus, dyslipidaemia, extra-musculoskeletal manifestations (uveitis, psoriasis, Crohn's disease, ulcerative colitis). Analyses for each outcome additionally included the respective diseases in the PS model. Individuals were censored after date of the last entry in their electronic health record. Stop date of each drug was not reliably available, therefore intention to treat analyses were performed at 1, 3 and 5 years. <h3>Results:</h3> Of 2,849 and 32,694 SpA patients starting JAKi (mean age 51±13 years, 35% male, 80% white) and TNFi (48±14 years, 49% male, 75% white), 2,844 in each group remained after PS-matching (SMD&lt;0.1 for all matched variables). Compared to TNFi, JAKi was not associated with risk of CVD (HR 0.779; 95% 0.547, 1.108), VTE (HR 0.827; 0.480, 1.425) or cancer (HR 0.820; 0.546, 1.231) at 1 year, but was associated with higher risk of herpes zoster (HR 1.855; 1.151, 2.991). When comparing JAKi initiators to 13,390 starting IL17i (50±13 years, 42% male, 75% white), 2,792 in each group remained after PS-matching (SMD&lt;0.1 for all matched variables). Compared to IL17i, JAKi was not associated with risk of CVD (HR 1.083; 0.732,1.603), VTE (HR 0.900; 0.504,1.607) or cancer (HR 0.890; 0.588,1.348) at 1 year. Results were directionally concordant for years 3 and 5 for all analyses. <h3>Conclusion:</h3> Among a large population of people with SpA (predominantly PsA), JAKi was not associated with increased risk of CVD, VTE or selected cancers, compared to TNFi or IL-17i. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Sizheng Steven Zhao UCB, Abbvie, Novartis, David Riley: None declared, Philip Austin: None declared, Gema Hernandez: None declared, Uazman Alam Procter and Gamble, Viatris, Eli Lilly, Sanofi.