P0746Endoscopic and histologic results from the UNITI Jr study of ustekinumab in paediatric Crohn’s Disease

Abstract Background Endoscopic and histological healing are treatment targets in adults with IBD, but more research is needed to validate these treatment outcomes in pediatric patients.1 The UNITI Jr study evaluated the efficacy of ustekinumab in paediatric patients with active Crohn’s disease (CD), including endoscopic and exploratory histologic assessments. Methods UNITI Jr (NCT04673357), a multicenter, phase 3 study enrolled 101 paediatric participants (≥2–18 years) with moderately-to-severely active CD (PCDAI score 30), and ileocolonoscopic ulceration (assessed by SES-CD). Other determinants of CD severity included increased C-reactive protein (≥3.0 mg/L) or calprotectin (≥250 μg/g)). Participants received 1 open-label IV ustekinumab dose (Induction) followed by randomization (N = 97) at Week (W)8 to SC ustekinumab every 8 or 12-weeks up to 52 weeks (Maintenance). Ustekinumab dosing was based on body-surface-area (250 mg/m2for participants 40kg) or weight-tiered (6 mg/kg for participants ≥40kg). Participants underwent ileocolonoscopies at screening, W16, and W52. Endoscopic and histologic response and remission (using SES-CD scores RHI indices derived from Geboes) were evaluated by blinded readers at W16 in randomized participants and W52 in induction responders. Summary statistics were computed. No formal statistical testing was performed but Confidence Interval (CI)s were provided. Results Across 97 randomized participants, the median (IQR) age was 14.0 (12.0-16.0), PCDAI 40.0 (35.0-45.0) and 27 weighed 40kg. Fifty-seven had ileocolonic disease, 9 had ileal-only disease, and 17 had colonic-only disease. The median (IQR) baseline SES-CD was 12.0 (7.0-19.0) and 94 (97.9%) participants had baseline SES-CD ≥3. Baseline histologic disease activity by RHI was observed in 82/95 (86.3%) of participants. 84.2% of participants at W8 achieved clinical response to induction therapy. At both W16 and W52, endoscopic, histologic, and combined histo-endoscopic index scores for remission and response were observed (Table 1). These outcomes, stratified by weight category (30kg, ≥30–40kg, ≥40kg), are summarized in Table 2. Endoscopic and histologic response and remission rates were comparable between the q12w and q8w treatment groups at W52, with overlapping CIs. Conclusion Endoscopic response and remission were observed in ustekinumab-treated paediatric patients. While histology and combined histo-endoscopic measures have not yet been validated for pediatric CD, the data suggest that treatment with ustekinumab can improve histologic and endoscopic outcomes in pediatric patients with moderately to severely active CD. Reference: Turner D, et al. Gastroenterology. 2021 Apr 1;160(5):1570-83. Conflict of interest: De Greef, Elisabeth: Advisory Board J & J, received medical writing support from Johnson & Johnson. Turner, Dan: Received consultation fee, research grant, royalties, or honorarium from Johnson & Johnson, Pfizer, Shaare Zedek Medical Center, Hospital for Sick Children, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, and Merck, received medical writing assistance from Johnson & Johnson Kierkuś, Jarosław: Received a grant from Nestle for the study research conducted, received medical writing support from Johnson & Johnson Korczowski, Bartosz: A grant was received from Johnson & Johnson and Takeda to conduct scientific research, received medical writing support from Johnson & Johnson Meglicka, Monika: Received consultation fees, royalties from Sandoz and Ferring, received medical writing support from Johnson & Johnson Russell, Richard K.: Received consultation fees, research grant, royalties, or honorarium from Johnson & Johnson, Pfizer, Ferring, Celltrion, Lilly & AlfaSigma, received medical writing support from Johnson & Johnson Cohen, Stanley: Consultant, Janssen, Kate Farms, research grants last 3 years, Janssen, Abbvie, Nutrition4Kids, LLC, received medical writing support from Johnson & Johnson Hyams, Jeffrey: Advisory board for Johnson & Johnson, Lilly, and AbbVie was/is a consultant for Takeda, Roche, and Boehringer Ingelheim, received medical writing support from Johnson & Johnson Griffiths, Anne: Received consultation fee, research grant, royalties or honorarium from Abbvie, Alfasigma, Janssen, Lilly, Merck, Pfizer, Shaare Zedek Medical Centre, SickKids Hospital, and Takeda, received medical writing support from Johnson & Johnson Rosh, Joel: Served/serves as an advisor and consultant for Abbvie serves/served as an advisor, consultant, and medical monitor for Janssen, received medical writing support from Johnson & Johnson Strauss, Richard: Employee of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson, received medical writing support from Johnson & Johnson Van Limbergen, Els: Employee of Johnson & Johnson and hold stock or stock options in Johnson & Johnson, received medical writing assistance from Johnson & Johnson Adedokun, Omoniyi: Employee of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson, received medical writing assistance from Johnson & Johnson Kim, Lilianne: I’m an employee of Johnson and Johnson and I hold stocks in the company, received medical writing assistance from Johnson & Johnson Branigan, Patrick: I am an employee of Johnson & Johnson and own stock in Johnson & Johnson, received medical writing support from Johnson & Johnson Volger, Sheri: Employed by Johnson & Johnson and have stock in the company, received medical writing support from Johnson & Johnson Dr. Cheng, Edaire: Employee of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson, received medical writing support from Johnson & Johnson