POS0110 INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS STRATIFIED BY GEOGRAPHIC REGION AND BASELINE CARDIOVASCULAR RISK: A POST HOC ANALYSIS OF ORAL SURVEILLANCE

Abstract

BackgroundORAL Surveillance was a post-authorisation safety study of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in patients (pts) with rheumatoid arthritis (RA) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX).ObjectivesTo examine associations between major adverse CV events (MACE) and the geographic region and baseline (BL) CV risk profile of pts 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 in North America [NA] or etanercept 50 mg once weekly in the rest of the world [RoW]). Incidence rates (IRs; pts with first events/100 pt-yrs) were evaluated for adjudicated MACE, as well as myocardial infarction (MI) and stroke. MACE was defined as CV death (excluding CV death due to pulmonary embolism), non-fatal MI and non-fatal stroke. IRs were stratified by geographic region (NA vs RoW) and BL CV risk profile: pts were first categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were then categorised by 10-yr risk of MACE (high [≥20%], intermediate [≥7.5–<20%], borderline [≥5–<7.5%] and low [<5%] risk), per the ASCVD-pooled cohort equations calculator1 with a 1.5 multiplier applied.2ResultsOverall, 4362 pts were included in the study (tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451). Across treatments, a higher proportion of pts in NA vs RoW had a HxCAD (Table 1). In pts without a HxCAD, across treatments, higher percentages of pts had a high 10-yr risk of MACE in NA vs RoW (Table 1). Across treatments, overall MACE IRs were higher in pts in NA vs RoW (Figure 1). Incidence and risk of MACE were higher with tofacitinib vs TNFi in both NA and RoW (Figure 1). In NA, MACE IRs were higher for tofacitinib 5 mg BID vs TNFi in pts with a HxCAD, and tofacitinib 10 mg BID vs TNFi for pts with a high 10-yr risk of MACE; pts with low or borderline 10-yr MACE risk had no MACE across tofacitinib groups (Figure 1). Compared with NA, similar trends for MACE were generally observed across treatments in RoW, particularly for intermediate, borderline and low CV risk categories (Figure 1).Table 1.Percentages of pts in NA and RoW with a HxCAD and pts without a HxCAD categorised by 10-yr risk of MACE, per ASCVD-pooled cohorts equation risk calculator1 with a 1.5 multiplier applied2NAaRoWTofacitinib 5 mg BID (N=402)Tofacitinib 10 mg BID (N=409)TNFib (N=432)Tofacitinib 5 mg BID (N=1053)Tofacitinib 10 mg BID (N=1047)TNFib (N=1019)HxCAD, n (%)58 (14.4)64 (15.6)81 (18.8)103 (9.8)108 (10.3)83 (8.1)No HxCAD: 10-yr risk of MACE, n (%)High (≥20%)97 (24.1)108 (26.4)113 (26.2)177 (16.8)195 (18.6)183 (18.0)Intermediate (≥7.5–<20%)131 (32.6)144 (35.2)137 (31.7)359 (34.1)372 (35.5)368 (36.1)Borderline (≥5–<7.5%)49 (12.2)31 (7.6)31 (7.2)151 (14.3)143 (13.7)124 (12.2)Low (<5%)60 (14.9)54 (13.2)65 (15.0)253 (24.0)218 (20.8)250 (24.5)Missing data7 (1.7)8 (2.0)5 (1.2)10 (0.9)11 (1.1)11 (1.1)HxCAD was defined as any history of MI, coronary heart disease, stable angina pectoris or coronary artery procedures. aUnited States, Puerto Rico and Canada. bFor pts randomised to the TNFi group, adalimumab and etanercept were administered in NA and RoW, respectivelyn, number of pts with specified characteristics; N, number of evaluable ptsConclusionThis post hoc analysis of data from ORAL Surveillance suggests that differences in MACE IRs across geographic regions are largely driven by HxCAD and high BL CV risk scores in NA vs RoW. Results should be interpreted with caution due to low pt and event numbers, particularly restricting the evaluation of tofacitinib vs TNFi in NA and RoW. Noting this limitation, these findings emphasise the importance of assessing and addressing BL CV risk when treating pts with RA.