Safety of ustekinumab in inflammatory bowel diseases: integrated safety analysis of results from phase 2 and 3 studies in crohn's disease and ulcerative colitis

Introduction: Ustekinumab (UST) is a well‐established therapy in Crohn's disease (CD) and psoriatic diseases. Recently presented phase 3 data showed that UST was safe and effective in ulcerative colitis (UC). Phase 3 induction and maintenance studies of UST in CD (UNITI, IMUNITI) and UC (UNIFI) had similar designs, which allows for integrated analysis across both inflammatory bowel disease (IBD) indications. Aims &Methods: We present an analysis of integrated safety data of UST in IBD. Data from 6 phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year of follow‐up. In phase 3, CD and UC pts received a single IV placebo (PBO) or UST (130mg or ~6mg/kg) induction dose followed by SC maintenance doses of PBO or UST (90mg q8 or q12 wks). Concomitant immunomodulators (IMM) and corticosteroids were permitted. All pts who received ≥1 dose of UST were included. Safety outcomes through 1 year are presented as the number of pts with events per 100 pt‐years (PY) of follow‐up Results: At induction baseline (2370 pts in pooled phase 3 IBD studies), median age was 38.0 years, 46.9% were receiving corticosteroids, 30.8% were receiving IMM, 53.0% had failed biologics, and 37.1% were naive to biologics. In phase 3 IBD studies, through Wk8 of PBO‐controlled induction, 1582 pts were treated with UST. Pts with ≥1 event (PBO vs UST) were 55.8% vs 53.9% with AEs, 6.2% vs 4.4% with SAEs, 19.9% vs 19.3% with infections, and 1.3% vs 1.1% with serious infections. Through 1 year in pooled phase 2/3 IBD studies, 2574 pts were treated with UST with 1733 PY. The number of patients per 100 PY with AEs (PBO 165.99 vs UST 118.32), SAEs (27.50 vs 21.23), infections (80.31 vs 64.32), serious infections (5.53 vs 5.02), malignancies including non‐melanoma skin cancer (NMSC) (0.50 vs 0.81), and discontinuations of study agent because of an AE (13.41 vs 7.73) were similar between UST and PBO. The most frequently occurring AEs (excluding diseases under study) were arthralgia (PBO 16.93 vs UST 16.56), headache (16.43 vs 16.50), nausea (13.25 vs 11.94), and abdominal pain (14.59 vs 11.54), and infections were nasopharyngitis (16.26 vs 18.11) and upper respiratory tract infection (11.40 vs 11.36). Results were similar for the CD and UC studies separately (Table shows key safety events). (Table Presented) [Number of pts with key safety events through 1 year of treatment per 100 PY of follow‐up (number of patients with events) in phase 2/3 CD &UC studies] Regarding serious infections, the CD‐specific manifestation of anal abscess occurred in PBO 2.02 and UST 0.90 pts per 100 PY in CD pts. When CD‐specific events were excluded, overall rates of serious infections were similar between UC and CD populations. In pooled phase 2/3 studies, the only malignancy (excluding NMSC) reported in >1 UST‐treated pt was prostate cancer; no lymphomas were reported through 1 year. Two pts receiving UST (0.12 per 100 PY; both had UC) died from events that investigators considered to be unrelated to study agent (esophageal varices hemorrhage and acute respiratory failure during thyroid surgery). Conclusion: The safety profile of UST in pts with UC and across integrated IBD indications through 1 year was favorable and consistent with the established safety profile in pts with CD and psoriatic disease.