ASSOCIATION BETWEEN BASELINE STATIN TREATMENT AND MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OF ORAL SURVEILLANCE

Background: ORAL Surveillance (NCT02092467) was a post-authorisation safety study of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in patients (pts) with rheumatoid arthritis (RA) aged ≥50 years (yrs) with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX). Statins are used to treat coronary artery disease (CAD) and are recommended by the American College of Cardiology/American Heart Association (ACC/AHA) for the management of pts at risk of atherosclerotic CV disease (ASCVD), such as those with ≥7.5% 10-yr risk of major adverse CV events (MACE) or diabetes mellitus. Objectives: To examine the association between baseline (BL) statin use and MACE in ORAL Surveillance. Methods: Pts with RA on stable MTX were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or TNFi (adalimumab 40 mg every 2 weeks or etanercept 50 mg once weekly). Pts were stratified post hoc by BL statin use (yes/no). Pts were further categorised by history of CAD (HxCAD), BL CV risk score per ACC/AHA guidelines (for pts without HxCAD; 10-yr risk of MACE per the ASCVD-pooled cohort equations risk calculator with a 1.5 multiplier applied ), and separately by BL diabetes status. CV risk score/BL diabetes status categories were: high (≥20%)/HxCAD (yes), intermediate (≥7.5–<20%) or low-borderline (<7.5%), and diabetes status (yes). For the overall population and each treatment group, risk of MACE was compared between BL statin use (yes vs no) via Cox analyses for each CV risk category and diabetes status (yes). Incidence rates (IRs; pts with first events/100 pt-yrs) and hazard ratios (HRs; BL statin use: yes vs no) were evaluated for adjudicated MACE. Results: Of 4362 pts (tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451), 497 had a HxCAD, and 3813 without a HxCAD had CV risk scores determined; 789 had BL diabetes. Overall, 1020 (23.4%) pts reported BL statin use. Across CV risk score categories for all treatment groups, <50% of pts received statins at BL, with statin use highest in the high/HxCAD category pts (35.7–40.6%) and pts with diabetes (35.7–44.2%) ( Table 1 ). Across categories, no interpretable associations between BL statin use and MACE were found. However, in the overall population, MACE IRs were lower in pts with vs without BL statin use in the high/HxCAD category, and in pts with diabetes ( Figure 1 ). In pts receiving tofacitinib 5 mg BID and TNFi, MACE IRs were lower in pts with vs without BL statin use across all categories ( Figure 1 ). Table 1. Proportion of pts receiving statins at BL, by CV risk category and presence of diabetes n/N (%) Overall Tofacitinib Tofacitinib TNFi 5 mg BID 10 mg BID High (≥20%)/HxCAD 525/1370 (38.3) 168/435 (38.6) 193/475 (40.6) 164/460 (35.7) Intermediate (≥7.5–<20%) 302/1511 (20.0) 110/490 (22.4) 94/516 (18.2) 98/505 (19.4) Low-borderline (<7.5%) 178/1429 (12.5) 66/513 (12.9) 57/446 (12.8) 55/470 (11.7) Diabetes (yes) 320/789 (40.6) 111/251 (44.2) 114/272 (41.9) 95/266 (35.7) N, number of pts in each category; n, number of pts receiving BL statins Conclusion: In this post hoc analysis of data from ORAL Surveillance, most pts did not receive BL statin treatment. This suggests suboptimal CV risk management, particularly in pts at high risk of CV events. There was no interpretable association between BL statin use and MACE. However, pts in the higher risk categories, particularly those receiving tofacitinib 5 mg BID, had lower MACE IRs with vs without BL statin use. This analysis did not take into account initiation or dose adjustment of statin treatment during the study, and had low yrs of exposure in some categories. REFERENCES: [1]Arnett et al. J Am Coll Cardiol 2019; 74: e177-232. [2]American College of Cardiology, American Heart Association. ASCVD risk estimator. https://tools.acc.org/ldl/ascvd_risk_estimator/index.html# !/calulate/estimator/. [3]Agca et al. Ann Rheum Dis 2017; 76: 17-28. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Lauren Hogarth, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: Jon T Giles Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Genentech, Gilead Sciences and UCB, Grant/research support from: Pfizer Inc, Christina Charles-Schoeman Consultant of: AbbVie, Gilead Sciences, Pfizer Inc and Sanofi-Regeneron, Grant/research support from: AbbVie, Bristol-Myers Squibb and Pfizer Inc, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Eli Lilly, Gilead Sciences, MSD, Pfizer Inc and Roche, Grant/research support from: Pfizer Inc, Roche and UCB, Maxime Dougados Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Zoltán Szekanecz Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer Inc, Roche and Sanofi, Paid instructor for: AbbVie, Eli Lilly, Gedeon Richter, Novartis, Pfizer Inc and Roche, Consultant of: AbbVie, Eli Lily, Novartis, Pfizer Inc, Roche and Sanofi, Steven R. Ytterberg Consultant of: Corbus Pharmaceuticals, Kezar Life Sciences and Pfizer Inc, Gary G Koch Shareholder of: IQVIA, Grant/research support from: AbbVie, Acceleron, Amgen, Arena, AstraZeneca, Cytokinetics, Eli Lilly, Gilead Scienes, GlaxoSmithKline, Huya Bioscience International, Johnson & Johnson, Landos Biopharma, Merck, Momentum, Novartis, Otsuka, Pfizer Inc, Sanofi and vTv Therapeutics, Employee of: University of North Carolina at Chapel Hill, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Sujatha Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Yan Chen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Teoman Yusuf Cesur Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose L. Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer SLU, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Deepak L Bhatt Grant/research support from: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, Novo Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic and The Medicines Company. Citation: , volume 81, supplement 1, year 2022, page 518Session: Rheumatoid arthritis - prognosis, predictors and outcome (POSTERS only)