Background: The efficacy and safety of the oral JAKi upadacitinib (UPA) has been evaluated for several rheumatic diseases. The objective of this analysis is to describe the long-term safety profile of UPA across RA, PsA, and AS from the SELECT clinical program.

Methods: Safety data (cut-off: 30 June 2020) from the UPA SELECT clinical program were compiled for RA (6 trials), PsA (2 trials), and AS (1 trial) for this analysis. Treatment-emergent adverse events (TEAEs; onset on or after first dose and ≤30 days after last dose for UPA and methotrexate [MTX] or ≤70 days for adalimumab [ADA]) were summarized for RA (pooled UPA 15 mg once daily [QD], ADA 40 mg every other week [EOW], and MTX), PsA (pooled UPA 15 mg QD and ADA 40 mg EOW), and AS (UPA 15 mg QD). TEAEs are reported as exposure-adjusted adverse event rates (EAERs; events/100 patient-years [E/100 PY]).

Results: In total, 4298 patients (RA, N = 3209; PsA, N = 907; AS, N = 182) received ≥1 dose of UPA 15 mg, totaling 8562 PY of exposure, with the majority of exposure from RA studies. AEs leading to discontinuation were generally similar across all treatment groups (UPA, ADA, and MTX) and patient populations (RA, PsA, and AS). Rates of serious infection and opportunistic infection were generally similar across all treatment groups within each population and across RA, PsA, and AS. No serious infections were reported in patients with AS. Herpes zoster and increased CPK were reported more often with UPA compared to ADA or MTX, with UPA showing similar rates of herpes zoster across RA, PsA, and AS. Malignancies excluding NMSC were reported at similar rates across all treatment groups and populations. NMSC was not common, with numerically higher rates observed with UPA versus MTX and/or ADA in RA and PsA. Similar rates of adjudicated MACE and adjudicated VTE were observed across all treatment groups, with no events reported in patients with AS. Rates of death reported in these clinical studies were not higher than expected in the general populations. As anticipated for the patient populations, the most common cause of death observed was cardiovascular in nature.

Conclusions: With the exception of herpes zoster, EAERs were generally similar across UPA, ADA, and MTX in RA, as well as UPA and ADA in PsA. No new safety risks were identified with long-term treatment in RA, PsA, or AS. UPA 15 mg demonstrated a consistent safety profile across RA, PsA, and AS populations in the SELECT clinical program.