Safety Profile of Upadacitinib in Psoriatic Arthritis: Integrated Analysis from Two Phase 3 Trials

Abstract

Aim: Upadacitinib (UPA) has shown efficacy and safety in patients (pts) with active PsA in the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials. We present the integrated safety data from the placebo (PBO)-controlled 24-week period of the clinical program.

Methods: The SELECT-PsA program enrolled pts with prior inadequate response (IR) or intolerance to ≥1 non-biologic DMARD (non-bDMARD) and prior IR or intolerance to ≥1 bDMARD. Both trials evaluated PBO, UPA 15 mg once daily (QD; UPA15) and UPA 30 mg QD (UPA30); SELECT-PsA 1 also included the active comparator adalimumab (ADA). The number and percentage of pts with TEAEs through Week 24 are presented.

Results: The rates of TEAEs, serious AEs, and AEs leading to study drug discontinuation (D/C) were similar with PBO and UPA15 and higher with UPA30. Rates of serious infection (SIs) and herpes zoster (HZ) were similar with PBO and UPA15 and higher with UPA30. The number of adjudicated major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE) was < 0.5% for all arms, with similar rates reported with PBO, UPA15, and UPA30; all pts had at least one risk factor. VTEs included 1 deep vein thrombosis in PBO and 1 pulmonary embolism each in the two UPA arms. CPK elevations were reported more frequently in the UPA arms vs PBO and were mostly asymptomatic, and rarely led to study drug D/C; no rhabdomyolysis was reported. The safety profile was generally consistent between UPA15 and ADA, except for lower rates of HZ, anaemia, and lymphopaenia and higher rates of hepatic disorders and neutropaenia in the ADA arm.

Conclusion: The safety profiles of UPA15 and ADA were generally consistent. The safety profile of UPA15 and UPA30 in PsA pts demonstrated consistent results compared to what has been observed with UPA in RA pts.