Aims: Describing the events and risk factors for MACE and VTE in the RA, PsA, and AS clinical trial programs of upadacitinib (UPA).

Methods: Treatment-emergent adverse events (TEAEs) of MACE and VTE for UPA 15 mg, UPA 30 mg, adalimumab (ADA) 40 mg, and MTX from 9 (6 RA; 2 PsA; 1 AS) phase 2b/3 trials were adjudicated by a blinded, independent committee, and reported as exposure adjusted event rates (EAERs) per 100 patient-years. Patients were not censored at the time of event. Time-to-event was analyzed by Kaplan-Meier method. Univariable analyses assessed risk factors for MACE and VTE in UPA patients.

Results: Across trials, 4298 patients received ≥ 1 dose of UPA 15 mg, 2125 received UPA 30 mg, 1008 received ADA 40 mg, and 314 received MTX. At baseline, 40%–50% of patients had ≥2 CV risk factors, and 6%–23% were ≥ 65 years-old. Of the 41 MACE reported with UPA 15 mg across RA and PsA, only 2 RA patients did not have ≥ 1 CV risk factors at baseline. There were 2 fatal VTEs, both in the RA UPA 15 mg group. Confidence intervals overlapped across UPA doses and comparators for MACE and VTE rates in RA and PsA. There was no pattern of time-to-event in patients receiving UPA. In univariable analyses, factors potentially associated with MACE or VTE in RA patients receiving UPA 15 mg included age ≥ 65 years; baseline hypertension; diabetes mellitus; smoking; history of CV event or VTE; and use of aspirin, statins, or antithrombotics. In PsA, aspirin use was associated with increased MACE risk.

Conclusion: Rates of MACE and VTE with UPA were infrequent and consistent with background rates in RA, PsA, and AS populations. The patient characteristics found to be associated with MACE and VTE are known risk factors.