Long-term cumulative safety of ustekinumab in bionaive patients with Crohn's Disease and Ulcerative Colitis

Abstract Background Ustekinumab (UST) is an approved biologic for the treatment of adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]). Previously, an integrated analysis of safety data through up to 5 years (yrs) showed a favourable safety profile for UST that was generally similar to placebo (PBO) in patients (pts) with IBD, and to the well-established safety profile across other approved indications. Several treatment options exist for newly diagnosed pts with moderate to severe IBD; therefore, long-term safety data from bionaive pts are important to help inform treatment selection in this population. Here, we present an integrated analysis incorporating UST Phase 2/3 long-term safety data from IBD studies through up to 5 yrs in CD and 2 yrs in UC for bionaive pts. Methods Data from 4 Phase 2/3 UST IBD studies were pooled. In Phase 3, pts received a single IV PBO or UST (130mg or ~6mg/kg) induction dose followed by SC maintenance doses of PBO or UST (90mg q8w or q12w). Patients identified as bionaive (never treated with a biologic) were included in the analysis of data through up to 5 yrs in CD and up to 2 yrs in UC. Concomitant immunomodulators and corticosteroids were permitted. All pts who received ≥1 UST dose were included. Safety outcomes are presented as event rates per 100 patient yrs (PY) of follow-up and 95% confidence interval (CIs). Bionaive UST data from the SEAVUE study (N=191) adjusted for exposure with events per 100 PY, will be shown for comparison. Results Through up to 5 yrs, 425 bionaive IBD pts received PBO (376 PYs) and 771 pts received UST (1511 PYs). Mean duration of follow-up (weeks) for PBO and UST was similar through 1 yr, and >2-fold longer for UST though 5 yrs. Rates per 100 PY for adverse events (AEs), serious AEs, infections, serious infections, major adverse cardiac events (MACE), and malignancies were similar between PBO and UST through up to 1 yr in bionaive IBD pts (Table 1). Rates per 100 PY for AEs, serious AEs, infections, serious infections, and MACE were similar and/or numerically lower for UST vs PBO through up to 5 yrs (Table 2). Overall, malignancies were infrequently reported through up to 5 yrs. Malignancy rates in bionaive UST pts were not significantly different than PBO through 1 yr (PBO: 0.44; UST: 0.34) or through 5 yrs (PBO: 0.27; UST: 0.46). A total of 2 deaths were reported in bionaive pts treated with UST through up to 5 yrs (0.13/100 PY); both assessed as unrelated (Table 3). Conclusion The safety profile of UST in the long-term IBD pooled safety dataset was favourable among bionaive pts and consistent with the well-established safety profile across approved indications.