P457 Long-term cumulative safety of ustekinumab in bionaive patients with Crohn’s Disease and Ulcerative Colitis

Danese, S.(1);Hanauer, S.B.(2);Jairath, V.(3,4);Mihaly, E.(5);Vicente Lidón, R.(6);Ott, E.(7);Gasink, C.(7);Miao, Y.(8);Ma, T.(8);Marano, C.(8);Sands, B.E.(9);

(1)IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy;(2)Northwestern University, Feinberg School of Medicine, Chicago, United States;(3)University Hospital, Division of Gastroenterology- Department of Medicine, London, Canada;(4)Western University, Division of Epidemiology and Biostatistics, London, Canada;(5)Semmelweis University, Department of Internal Medicine, Budapest, Hungary;(6)Hospital Universitario Miguel Servet, Inflammatory Bowel Disease Unit, Zaragoza, Spain;(7)Janssen Scientific Affairs- LLC, Immunology, Horsham, United States;(8)Janssen Research & Development- LLC, Immunology, Spring House, United States;(9)Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, United States;


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.


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.


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).
Table 1. Key safety events through 1 year of treatment in IBD studies1 among bionaive patients; numbers of events per 100 PYs of follow-up with 95% CIs
Table 2. Key safety events through 5 years of treatment in IBD studies1 among bionaive patients; numbers of events per 100 PYs of follow-up with 95% CIs
Table 3. Deaths in bionaive patients in IBD pooled safety dataset


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.