POS0237 MAJOR ADVERSE CARDIOVASCULAR EVENTS, MALIGNANCIES AND VENOUS THROMBOEMBOLISM BY BASELINE CARDIOVASCULAR RISK: A POST HOC ANALYSIS OF ORAL SURVEILLANCE

Abstract

Background: ORAL Surveillance was a post-authorisation safety study of tofac-itinib vs TNF inhibitors (TNFi) in rheumatoid arthritis (RA) patients (pts) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX). CV disease has overlapping risk factors with malignancies and venous thromboembolism (VTE), including older age, smoking, hypertension and diabetes.1,2 Objectives: To evaluate the impact of pts' baseline (BL) CV risk on the incidence and risk of major adverse CV events (MACE), malignancies and VTE in ORAL Surveillance. Methods: Pts on stable MTX were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or a TNFi (adalimumab 40 mg every 2 weeks or etaner-cept 50 mg once weekly). Incidence rates (IRs; pts with frst events/100 pt-yrs) and hazard ratios (HRs; tofacitinib vs TNFi) were evaluated for adjudicated MACE (defned as CV death [excluding CV death due to pulmonary embolism (PE)], non-fatal MI and non-fatal stroke), malignancies (excluding NMSC) and VTE (including fatal/non-fatal deep vein thrombosis and PE). Across safety outcomes, IRs/HRs were stratifed by BL CV risk score: pts were frst categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were further stratifed by BL CV risk score categories (high [≥20%], intermediate [≥7.5-<20%], borderline [≥5-<7.5%] and low [<5%] risk), with a 1. 5 multiplier applied per EULAR recommendations.3 Results: 4362 pts were included: tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451. In these treatment groups, during a median follow-up of 4.0 yrs, MACE was reported in 47 (3.2%), 51 (3.5%) and 37 (2.6%) pts, malignancies in 62 (4.3%), 60 (4.1%) and 42 (2.9%) pts, and VTE in 17 (1.2%), 34 (2.3%) and 10 (0.7%) pts, respectively. Approximately two-thirds of pts had intermediate to high CV risk, or HxCAD, and risk was well-balanced across treatment groups (Table 1). Across treatments, MACE and malignancies IRs were highest in pts with a HxCAD or a high BL CV risk score (Figure 1). IRs/HRs for MACE, malignancies and VTE were generally higher with tofacitinib vs TNFi. Differences between tofacitinib vs TNFi in MACE and malignancy IRs/HRs were typically more pronounced in pts with a HxCAD or at least intermediate BL CV risk score, and less so in pts with lower BL CV risk score (Figure 1). In tofacitinib 10 mg BID-treated pts, VTE IRs/HRs (vs TNFi) were clearly highest in pts with a HxCAD or high BL CV risk score; no association between VTE and BL CV risk scores was observed with tofacitinib 5 mg BID or TNFi (Figure 1). Conclusion: In this post hoc analysis of data from ORAL Surveillance, IRs for MACE and malignancies (excluding NMSC) were highest across treatments, and increased with both tofacitinib doses vs TNFi, in pts with a HxCAD or high BL CV risk score; a similar fnding was observed for VTE IRs in pts treated with tofac-itinib 10 mg BID. These fndings support recommendations to regularly assess and address CV risk in RA pts.