ASSOCIATION BETWEEN BASELINE CARDIOVASCULAR RISK AND INCIDENCE RATES OF MAJOR ADVERSE CARDIOVASCULAR EVENTS AND MALIGNANCIES IN PATIENTS WITH PSORIATIC ARTHRITIS AND PSORIASIS RECEIVING TOFACITINIB

Background: Common comorbidities of psoriatic arthritis (PsA) and psoriasis (PsO) are cardiovascular (CV) disease and metabolic syndrome (MetS). Risk of CV disease may be associated with increased risk of future malignancies. Tofacitinib is a JAK inhibitor for treatment of PsA and has been investigated for treatment of PsO. Objectives: To examine baseline (BL) CV risk and its association with incidence rates (IRs) of major adverse CV events (MACE) and malignancies in tofacitinib-treated patients (pts) with PsA and PsO. Methods: Analysis included data from 3 (Phase [P]3/long-term extension [LTE]) trials of pts with PsA and 7 (P2/3/LTE) trials of pts with PsO receiving ≥1 dose of tofacitinib (5 or 10 mg twice daily). IRs (pts with events/100 pt-yrs) for MACE and malignancies (excluding non-melanoma skin cancer) were stratified by: history of coronary artery disease (HxCAD [≥1 of myocardial infarction, coronary heart disease, coronary artery procedure or stable angina pectoris]); BL 10-yr atherosclerotic CV disease (ASCVD) risk (ASCVD-pooled cohort equations calculator [only in pts without HxCAD]); and BL MetS (≥3 of hypertension, raised triglycerides, reduced high-density lipoprotein cholesterol, high waist circumference or high fasting glucose levels). Results: Of 783 and 3663 pts with PsA and PsO, total tofacitinib exposure was 2038 and 8950 pt-yrs, and median duration of exposure was 3.0 and 2.4 yrs, respectively. In pts with PsA and PsO, 5.0% and 2.5% had HxCAD, respectively; in those without HxCAD, >20% had intermediate/high BL 10-yr ASCVD risk ( Figure 1 ). At BL, 40.9% and 32.7% of pts with PsA and PsO had MetS, respectively. IRs of MACE were greatest in pts with PsA and PsO who had HxCAD/high BL 10-yr ASCVD risk ( Table 1 ). In the PsA cohort, 5/6 pts with MACE had BL MetS. IRs of malignancies in pts with PsA were greatest in those with intermediate/high BL 10-yr ASCVD risk; 8/9 pts with malignancies in these risk categories had BL MetS ( Table 1 ). In the PsO cohort, IR of malignancies was notably greater in those with high vs low/intermediate BL 10-yr ASCVD risk ( Table 1 ). Table 1. IRs of MACE and malignancies in pts with PsA and PsO receiving tofacitinib, stratified by HxCAD, BL 10-yr ASCVD risk and BL MetS MACE Malignancies PsA PsO PsA PsO n/N[n1] IR (95% CI ) n/N[n1] IR (95% CI ) n/N[n1] IR (95% CI ) n/N[n1] IR (95% CI ) HxCAD Yes 1/39[0] 0.97 (0.02, 5.38) 3/93[0] 1.49 (0.31, 4.36) 0/39[0] 0.00 (0.00, 3.52) 0/93[0] 0.00 (0.00, 1.83) No 5/744[5] 0.25 (0.08, 0.59) 20/3570[10] 0.22 (0.13, 0.34) 15/744[10] 0.75 (0.42, 1.24) 60/3570[26] 0.66 (0.51, 0.85) BL 10-yr ASCVD risk category High risk (≥20%) 1/35[1] 1.26 (0.03, 7.01) 7/179[4] 1.67 (0.67, 3.43) 1/35[1] 1.26 (0.03, 7.03) 15/179[10] 3.57 (2.00, 5.89) Intermediate risk(≥7.5–<20%) 2/121[2] 0.62 (0.07, 2.23) 9/716[6] 0.50 (0.23, 0.95) 8/121[7] 2.46 (1.06, 4.86) 23/716[9] 1.28 (0.81, 1.92) Borderline risk(≥5–<7.5%) 1/91[1] 0.42 (0.01, 2.32) 2/400[0] 0.19 (0.02, 0.67) 2/91[1] 0.83 (0.10, 3.01) 5/400[1] 0.47 (0.15, 1.09) Low risk (<5%) 1/487[1] 0.08 (0.00, 0.42) 2/2241[0] 0.03 (0.00, 0.13) 4/487[1] 0.30 (0.08, 0.77) 17/2241[6] 0.30 (0.17, 0.47) BL MetS Yes 5/320 0.60 (0.20, 1.40) 10/1197 0.34 (0.16, 0.63) 10/320 1.20 (0.58, 2.21) 26/1197 0.89 (0.58, 1.31) No 1/463 0.08 (0.00, 0.44) 13/2466 0.20 (0.11, 0.35) 5/463 0.40 (0.13, 0.92) 34/2466 0.54 (0.37, 0.75) Follow-up time calculated up to the day of the first event and subject to risk period of 28 days beyond the last dose of study drug. CI, confidence interval; N, total pts; n, pts with MACE/malignancies; n1, pts with MACE/malignancies and BL MetS. Conclusion: In tofacitinib-treated pts with PsA and PsO, raised CV risk and MetS at BL were potentially associated with higher IRs of MACE and malignancies. Our findings support assessing CV risk in pts with PsA and PsO and enhanced monitoring for malignancies in those with raised CV risk. REFERENCES: [1]Karmacharya et al. Ther Adv Musculoskel Dis 2021; 13: 1-15. [2]Garshick et al. J Am Coll Cardiol 2021; 77: 1670-1680. [3]Lau et al. JACC CardioOncol 2021; 3: 48-58. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Mitchell, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: Lars Erik Kristensen Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc and UCB, Grant/research support from: Biogen, Janssen, Novartis and UCB, Bruce Strober Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen and Ortho Dermatologics, Consultant of: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Boehringer Ingelheim, Bristol-Myers Squibb, Cara, Celgene, Dermavant, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo, Meiji Seika Pharma, Novartis, Ortho Dermatologics, Pfizer Inc, Regeneron, Sanofi-Genzyme, Sun Pharma and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc and UCB, Consultant of: AbbVie, BIOCAD, Gilead Sciences, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer Inc, Samsung Bioepis and UCB, Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Ying Ying Leung Consultant of: AbbVie, Eli Lilly, Janssen and Novartis, Hyejin Jo Consultant of: Pfizer Inc, Employee of: Syneos Health, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ivana Vranic Shareholder of: Pfizer Inc, Employee of: Pfizer Ltd, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dafna D Gladman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc and UCB. Citation: , volume 81, supplement 1, year 2022, page 20Session: Clinical aspects in Psoriatic Arthritis (Oral Presentations)