Aim: The objective of this analysis is to describe the long-term safety profile of Upadacitinib (UPA) across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from the SELECT clinical program.

Method: Safety data from the UPA SELECT clinical program were compiled for RA (6 trials1), PsA (2 trials2), and AS (1 trial3). Treatment-emergent adverse events (TEAEs were summarized for RA (pooled UPA 15mg daily, ADA 40mg fortnightly, and MTX), PsA (pooled UPA15 mg daily and ADA 40mg fortnightly), and AS (UPA 15mg daily).

Results: 4298 patients received ≥1 dose of UPA 15mg, totaling 8562 PY, with the majority 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 them. Pneumonia was the most common serious infection and serious AE in RA and PsA. Herpes zoster (HZ) and increased CPK occurred more often with UPA compared to ADA or MTX. Malignancies excl NMSC occurred at similar rates across treatment groups and populations. NMSC was not common, with numerically higher rates with UPA versus MTX and/or ADA. Similar rates of adjudicated MACE and VTE were observed across all treatment groups. None were reported in AS. Rates of death were not higher than expected in the general populations. As anticipated, the most common cause of death observed was cardiovascular.

Conclusions: With exception of HZ and CPK elevations, EAER 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 15mg demonstrated a consistent safety profile across RA, PsA, and AS.