Background/Purpose: Patients (pts) with rheumatoid arthritis (RA) are at an increased risk for the development of venous thromboembolism (VTE, including pulmonary embolism [PE] and deep vein thrombosis [DVT]) vs the general population (~2-fold increase).¹ Beyond RA, additional risk factors have been described, with prior history of VTE and obesity posing particular risk. VTE events have been observed in pts receiving JAK inhibitors, including upadacitinib (UPA). We describe the incidence of VTE in pts with RA receiving UPA relative to active comparators in the phase 3 clinical trial program and to evaluate potential risk factors.

Methods: Adjudicated events of treatment-emergent VTE were determined in pts receiving UPA in an integrated analysis (data cut-off, 30 Jun 2019) of five randomized phase 3 trials (SELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, SELECT-COMPARE, and SELECT-BEYOND), of which 4 evaluated both the UPA 15 mg and 30 mg QD doses and 1 (SELECT-COMPARE) evaluated only UPA 15. Incidence of VTE was also determined in pts receiving adalimumab (ADA) + methotrexate (MTX) in SELECT-COMPARE and MTX monotherapy in SELECT-EARLY. Events are attributed to treatment received at time of event and are summarized per events/100 patient yrs. VTE risk factors were assessed using univariate Cox regression models.

Results: A total of 35 VTE events were observed across treatment groups. The exposure-adjusted treatment-emergent event rates (E/100 PYs, 95% CI) of VTE were 0.5 (0.3, 0.7) for UPA 15, 0.3 (0.1, 0.7) for UPA 30, 0.5 (0.1, 1.3) for ADA + MTX, and 0.4 (0.1, 1.6) for MTX, with no pattern to event onset across treatments. Events of PE, DVT, or both PE and DVT were reported across treatment groups (Table). Pts who experienced VTE, across all treatment groups, on average, were older than pts who did not (62/59/58/61 yrs vs 54/55/54/53 yrs for UPA 15, UPA 30, ADA + MTX, and MTX, respectively). The mean body mass index (BMI) of pts with VTE tended to be higher (34─40 for pts with VTE vs 28-29 kg/m² for those without). Across UPA treatment groups, 135/2629 (UPA 15) and 62/1204 (UPA 30) pts had a prior history of VTE; of these pts, 5 (3.7%) and 2 (3.2%) experienced VTE on UPA 15 and UPA 30, respectively. Univariate Cox regression models identified BMI and prior history of VTE as factors associated with VTE in the UPA 15 and 30 mg groups (Figure). Age and NSAID use were shown to be associated with VTE risk among pts in the UPA 15 but not 30 mg group.

Conclusion: VTE event rates appeared balanced across UPA doses and active comparator groups in pts with RA. Risk factors for VTE events identified through univariate analyses in pts who received UPA included prior history of VTE and BMI, two factors previously known to be associated with VTE risk. One limitation is the small sample size, limiting the analysis to univariate. Continued follow-up of pts receiving UPA is ongoing to further contextualize the risk of VTE in the clinical trial program.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-and-risk-of-venous-thromboembolic-events-among-patients-with-rheumatoid-arthritis-enrolled-in-the-upadacitinib-clinical-trial-program/