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

Abstract

BackgroundORAL Surveillance was a post-authorisation safety study of tofacitinib 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.1,2ObjectivesTo 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.MethodsPts 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 etanercept 50 mg once weekly). Incidence rates (IRs; pts with first events/100 pt-yrs) and hazard ratios (HRs; tofacitinib vs TNFi) were evaluated for adjudicated MACE (defined 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 stratified by BL CV risk score: pts were first categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were further stratified 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.3Results4362 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).Table 1.Percentages of pts with a HxCAD and pts without a HxCAD categorised by BL CV risk scores, per ASCVD-PCE risk calculator4 with a 1.5 multiplier applied3Tofacitinib 5 mg BID (N=1455)Tofacitinib 10 mg BID (N=1456)TNFi (N=1451)HxCAD, n (%)161 (11.1)172 (11.8)164 (11.3)No HxCAD: BL CV risk score, per ASCVD-PCE risk calculator, n (%)High (≥20%)274 (18.8)303 (20.8)296 (20.4)Intermediate (≥7.5–<20%)490 (33.7)516 (35.4)505 (34.8)Borderline (≥5–<7.5%)200 (13.7)174 (12.0)155 (10.7)Low (<5%)313 (21.5)272 (18.7)315 (21.7)Missing data17 (1.2)19 (1.3)16 (1.1)HxCAD is defined as any history of MI, coronary heart disease, stable angina pectoris or coronary artery procedures n, number of pts with specified characteristics; N, number of evaluable ptsConclusionIn 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 finding was observed for VTE IRs in pts treated with tofacitinib 10 mg BID. These findings support recommendations to regularly assess and address CV risk in RA pts.