Background/Purpose:   To describe the short-term safety experience of UST during the double-blind, PBO-controlled portion of the PsA & PsO clinical developmental programs.

Methods: Safety data for the PsA population were pooled from a Ph2 (n=146) & 2 Ph3 (PSUMMIT I [n=615], PSUMMIT II [n=312]) studies of UST in pts with active PsA. Safety data for the PsO population were pooled from 1 Ph2 (n=320) & 2 Ph3 (PHOENIX 1 [n=766] & PHOENIX 2 [n=1230]) studies of UST in pts with moderate-to-severe PsO, including a sub-grp of pts with documented PsA (history of or current) at baseline (BL) [n=628]. Pts were randomized to PBO, UST45mg, or UST90mg. The PBO-controlled period was 16wks for all PsA studies, 20wks for the Ph2 PsO study, & 12wks for Ph3 PsO studies. Concomitant therapy(i.e. stable doses of MTX/oral corticosteroids/NSAIDs) were permitted in PsA studies; no concurrent therapies for PsO/PsA were permitted in the PsO studies. Event rates for overall safety endpoints (overall AEs, infections, AEs leading to discontinuation, serious AEs [SAEs]) & AEs of interest (serious infections, nonmelanoma skin cancer [NMSC], other malignancies, major adverse CV events [MACE]) were analyzed & compared between the PBO & UST grps within each population. Data for the UST dose grps were analyzed & presented as a combined grp. All pts who received ≥1 dose of tx were included in the analyses. Results were reported as number of events per 100 pt-yrs of follow-up (PY).

Results: 1071 treated pts (379 PBO, 692 UST) were included in the PsA population & 2314 treated pts (732 PBO, 1582 UST) were included in the PsO population (including 207 PBO, 421 UST in PsA sub-grp). BL demographics & medical history were generally comparable between the PsA & PsO populations with similar proportions of pts reporting relevant comorbidities, including diabetes, hyperlipidemia, hypertension & family history of coronary heart disease.  In the PsA population, median duration of PsA at BL was ≥4 yrs & >75% had PsO with ≥3% BSA skin involvement. In the PsO population, median BSA involvement was 21%; median PASI score was 17 & 27% had PsA. Safety outcomes observed during the PBO-controlled period are detailed (Table). Within each population, rates of overall AEs, infections, & SAEs in pts receiving PBO or UST were generally comparable. Slightly higher rates of AEs leading to discontinuation were observed across all PBO grps & a slightly higher rate of SAEs was observed in the PBO grp in the PsA population. Event rates of AEs of interest were generally comparable, with overlapping confidence intervals, between the PBO & UST grps within the PsA & PsO populations.

Conclusion:   During the PBO-controlled portion of the studies, UST was well-tolerated in pts with PsA & PsO. Overall safety observations were consistent between both populations, & safety event rates were generally comparable between pts receiving PBO & UST within each population.