Introduction: Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment. Methods: Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or >16 weeks after the last UST dose for UST pts who switched to PBO. Results: Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a CD pt 10 months after receiving UST 130 mg IV) and UST pts (n=1) (Table). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1). Conclusion: Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 years with 13807 PYs of follow-up and not higher in UST pts vs PBO, suggesting no increased risk of OI with long-term UST treatment. Table 1. - Opportunistic infections (OIs) and active tuberculosis (TB) in Inflammatory Bowel Disease (CD, UC) and Psoriatic studies (PsO, PsA) through up to 5 yrs; numbers of events per 100 patient-years (PYs) of follow-up Inflammatory Bowel Disease Indications a Psoriatic Indications a All Approved Indications Pooled Placebo b (n=1389) Ustekinumab c (n=2575) Placebo d (n=1112) Ustekinumab e (n=4135) Placebo b,d (n=2501) Ustekinumab c.e (n=6710) Total PYs of follow-up 916 3960 327 9847 1244 13807 Average duration of follow-up (weeks) 34.31 79.97 15.30 123.83 25.86 107.00 All OIs, event rates per 100 PYs [n] 0.55 [5] 0.33 [13] 0.00 [0] 0.01[1] 0.40 [5] 0.10 [14] OIs excluding TB 0.33 [3] 0.30 [12] 0.00 [0] 0.01 [1] 0.24 [3] 0.09 [13] TB 0.22 [2] 0.03 [1] 0.00 [0] 0.00 [0] 0.16 [2] 0.01 [1] aPsoriatic (PsO and PsA) trials evaluated subcutaneous ustekinumab (UST) 45/90 mg or placebo (PBO), generally at week 0 and 4, then every 12 weeks (q12w). IBD (CD and UC) trials generally evaluated a single intravenous UST dose (130 mg or weight range-based dosing of ∼6 mg/kg) or PBO induction dose at week 0, followed by subcutaneous UST 90 mg at week 8, then q8w or q12w.bCD and UC: includes data up to the first UST dose for patients who were initially treated with PBO; includes data at or after 16 weeks from the first UST dose onward, up to the dose adjustment if patients had a dose adjustment, for patients who crossed-over or re-randomized to PBO maintenancecCD and UC: includes data up to 16 weeks from the first UST dose for patients who crossed-over or re-randomized to PBO maintenance, and from the dose adjustment onward if patients had a dose adjustment from subcutaneous PBO to subcutaneous UST 90 mg q8wdPsoriatic diseases: includes data up to the time of early escape or crossoverePsoriatic diseases: includes data from the first UST dose onward for patients who early escaped or crossed-over from PBO