William J. Sandborn, MD, FACG1, Subrata Ghosh, MD2, Christopher D. O’Brien, MD, PhD3, Elyssa Ott, MPH4, Colleen Marano, PhD3, Yiying Zhou, PhD3, Sheri Volger, MS3, Ilia Tikhonov3, Christopher Gasink, MD5, Silvio Danese, MD, PhD6, Bruce E. Sands, MD, FACG7
1University of California San Diego, La Jolla, CA; 2Institute of Translational Medicine and NIHR Biomedical Research Center, Birmingham, England, United Kingdom; 3Janssen Research & Development, LLC, Spring House, PA; 4Janssen Pharmaceuticals, LLC, Horsham, PA; 5Janssen Scientific Affairs, LLC, Horsham, PA; 6Humanitas University, Milan, Lombardia, Italy; 7Icahn School of Medicine at Mount Sinai, New York, NY
Introduction: Ustekinumab (UST) is a well-established therapy in Crohn’s disease (CD) and psoriatic diseases. UST was safe and effective in phase 3 ulcerative colitis (UC) studies. Pivotal studies of UST in CD (UNITI, IMUNITI) and UC (UNIFI) had similar designs, which allows for integrated analysis across both indications. We present an integrated safety analysis of UST in inflammatory bowel disease (IBD).
Methods: Data from 6 phase 2/3 studies were pooled, and safety was evaluated through 1 year of follow-up. In phase 3, 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 q8w or q12w). 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 patient-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 naïve to biologics.
In phase 3 IBD studies, through Wk8 of PBO-controlled induction, the frequency of key safety events was similar between UST and PBO (Table 1). In addition, through 1 year across phase 2/3 IBD studies (Table 2), numbers of pts per 100 PY with key safety events were similar between treatment groups. 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); infections were nasopharyngitis (16.26 vs 18.11) and upper respiratory tract infection (11.40 vs 11.36). For serious infections, the CD-specific event of anal abscess occurred in PBO 2.02 and UST 0.90 pts per 100 PY. When CD-specific events were excluded, overall rates of serious infections were similar between UC and CD.
The only malignancy (excluding NMSC) reported in >1 UST-treated patient 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).
Discussion: 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.
Citation: William J. Sandborn, MD, FACG; Subrata Ghosh, MD; Christopher D. O’Brien, MD, PhD; Elyssa Ott, MPH; Colleen Marano, PhD; Yiying Zhou, PhD; Sheri Volger, MS; Ilia Tikhonov; Christopher Gasink, MD; Silvio Danese, MD, PhD; Bruce E. Sands, MD, FACG. P0505 - 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. Program No. P0505. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.