P1154Safety and efficacy of ustekinumab in paediatric ulcerative colitis (UC): Results from the phase 3 UNIFI Jr study

Abstract Background The UNIFI Jr study (NCT04630028) evaluated efficacy and safety of ustekinumab in paediatric patients with moderately-to-severely-active ulcerative colitis (UC). Methods 112 patients (2 to 18 years; weight ≥10kg); moderately-to-severely active UC (baseline Mayo score ≥6, Mayo endoscopy subscore ≥2 and inadequate response or intolerant to conventional/biologic therapy or corticosteroid-dependent) received a single open-label, IV ustekinumab induction (I) dose. At Week (W)8, 109 patients were randomized in a 1:1 ratio stratified by weight (40kg/≥40kg) and W8 clinical response status (decrease from baseline BL in Modified Mayo score ≥30% and ≥2 points with decrease from BL rectal bleeding subscore ≥1 or rectal bleeding subscore ≤1) to receive blinded SC ustekinumab maintenance therapy Q8W/Q12W for 44-weeks. Ustekinumab dosing was based on body-surface-area (40kg) or weight-tier (≥40kg). Primary endpoints were clinical remission (Mayo subscores: stool ≤1 without an increase from BL, rectal bleeding 0, endoscopy 0-1 with no friability present) at W8 and at W52 in those with induction response at W8. Results Among 112 patients (median IQR age 14.0 11.0-15.5 years; 54.5% female; 60.7% biologic-naive); median (IQR) PUCAI score 55.0 (45.0-60.0), 91.7% moderate UC, median (IQR) Mayo score 8.0 (7.0-9.0), and 67.0% extensive UC. At W8, 79 patients achieved clinical response (induction responders). At Week 52, 32 of 79 (40.5% 95% CI: 30.4%-51.5%) clinical responders achieved clinical remission, 52 (65.8%) achieved symptomatic remission, 51 (64.6%) were in clinical remission by PUCAI (score 10), 32 (40.5%) achieved endoscopic improvement, 32 (40.5%) were corticosteroid-free for ≥90 days, and 29 (36.7%) had histologic-endoscopic mucosal improvement (Figure 1). Remission rate was higher in patients without prior biologic failures (25 47.2%; 95% CI: 34.4%-60.3%) compared to those with biologic failure (7 26.9%; 95% CI: 13.7%-46.1%)(Figure 2). Not having previously failed biologic therapy was associated with higher W52 remission rates. Remission rates were similar from W8 to W52 in all weight subgroups (Figure 2). Both Q8W and Q12W maintenance regimens were efficacious. During maintenance therapy, serious adverse events (SAE) occurred in 6.4% (7/109) of patients, most commonly reported SAEs were GI disorders (UC). AE rates were similar between Q8W/Q12W groups and treatment-emergent SAEs occurred in 9.3% (5/54) and 3.6% (2/55) of patients in Q8W/Q12W groups, respectively. Conclusion Ustekinumab induction and maintenance therapy was effective in treating paediatric patients aged 2 to 18 years with moderate-to-severe paediatric UC. Ustekinumab was well-tolerated with no new safety signals. Conflict of interest: De Greef, Elisabeth: Advisory Board Johnson & Johnson. Received medical writing assistance funded by Johnson & Johnson. Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Genentech Research support: Janssen, Abbvie, Takeda, Pfizer Received medical writing assistance funded by Johnson & Johnson Royalties: Shaare Zedek Medical Center, Hospital for Sick Children Russell, Richard K.: Grant: Nestec Other: Abbvie, Celltrion, Janssen, Lilly, Nestle, Pharmacosmos, Pfizer Received medical writing assistance funded by Johnson & Johnson Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda Received medical writing assistance funded by Johnson & Johnson Kierkuś, Jarosław: Grant: Nestle Other: Nutricia, Abbvie, Nestle Received medical writing assistance funded by Johnson & Johnson Korczowski, Bartosz: A grant was received from Johnson & Johnson and Takeda to conduct scientific research. Received medical writing assistance funded by Johnson & Johnson. Meglicka, Monika: Received consultation fees, royalties from Sandoz and Ferring Received medical writing assistance funded by Johnson & Johnson Cohen, Stanley: Consultant, Janssen, Kate Farms Research grants last 3 years, Janssen, Abbvie, Principal, Nutrition4Kids, LLC Received medical writing assistance funded by Johnson & Johnson Hyams, Jeffrey: Abbvie: Advisory Board Janssen: Advisory Board Roche/Genentech: Consultant Takeda: Consultant Received medical writing assistance funded by Johnson & Johnson Rosh, Joel: Advisor/Consultant: AbbVie, Janssen, Mesoblast. Received medical writing assistance funded by Johnson & Johnson. Strauss, Richard: Employee of Johnson & Johnson and may own stock or have stock options in Johnson & Johnson. Received medical writing assistance funded by Johnson & Johnson. Adedokun, Omoniyi: Employee Johnson & Johnson and may own stock or have stock options in Johnson & Johnson Received medical writing assistance funded by Johnson & Johnson Salas, Jose: Employee of Johnson & Johnson and may own stock/have stock options in Johnson & Johnson. Received medical writing assistance funded by Johnson & Johnson. Wang, Yuhua: Employee of Johnson & Johnson and hold Johnson & Johnson stocks and options. Received medical writing assistance funded by Johnson & Johnson. Dr. Ufberg, Paul: Employee of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson. Received medical writing assistance funded by Johnson & Johnson. Van Limbergen, Els: Employee of Johnson & Johnson and may own/have stock options in Johnson & Johnson. Received medical writing assistance funded by Johnson & Johnson.