P1010Exposure optimisation substudy (EOS) of ustekinumab in paediatric ulcerative colitis (UC): Q4W results from the phase 3 UNIFI Jr study

Abstract Background To examine efficacy, safety, and pharmacokinetics (PK) of ustekinumab (UST) in paediatric patients with moderate-to-severe UC in the UNIFI Jr (NCT04630028) Exposure Optimisation Substudy (EOS). Methods Patients (N = 112; 2 to 18 years; weight ≥10kg); moderate-to-severe UC, inadequate response/intolerant to prior treatment or corticosteroid-dependent) received one open-label IV UST induction dose in UNIFI Jr. At Week (W)8, patients were randomized 1:1 to blinded maintenance SC UST Q8W or Q12W for 44-weeks. Patients who lost response after W16 or were W16 induction nonresponders with low steady-state trough UST concentrations (1.4μg/mL) were eligible for entry in an optional EOS (≥16 weeks) with Q4W dosing. Patients were evaluated at W16 for clinical response (partial Mayo score) and clinical remission (PUCAI score). Results Of 109 patients randomised to maintenance, 97 were responders. Twenty-one (19.3%) went to a Q4W dosing in the EOS (4/109 3.7% were induction non-responders by W16; 17/97 17.5% had confirmed loss of response LOR and low UST levels during maintenance period). Key baseline demographics of the 21 patients treated in the EOS (Table): median IQR age was 14.0 9.0; 15.0 years; 12/21 (57.1%) had prior biologic failure; all patients had extensive colitis; 12/21 (57.1%) and 16/21 (76.2%) had elevated CRP and Fcal, respectively. Sixteen of 21 patients (76.2%) completed the 16-week EOS and 11/13 (84.6%) achieved clinical response (by partial Mayo score); 9/16 (56.3%) achieved clinical remission (by PUCAI score) at EOS W16 (Figure). Average PUCAI scores and partial Mayo scores from initiation of EOS decreased over time. Before administration of UST Q4W, median (mean) serum UST concentration was 0.38 (0.97) µg/mL. Following Q4W dosing, UST concentrations in paediatric patients increased to within the observed range of adults with UC receiving 90 mg Q8W (serum trough UST concentrations ranged from 0.86 to 7.18 µg/mL at substudy W12 in UNIFI Jr when this approximated steady-state). AE(s) were reported in 81.0% of patients (57.1% ≥1 infection, none serious) and 9.5% had SAE(s). Safety with SC UST Q4W dosing was generally consistent with the main study; no new or unexpected safety concerns were identified. Conclusion Patients enrolled in EOS responded favourably to UST Q4W dosing leading to both increased clinical response and remission associated with higher serum drug levels. Overall safety was comparable to that previously reported with UST. Trough levels of UST in patients treated in the EOS were within the range of those in adults receiving Q8W dosing. Conflict of interest: De Greef, Elisabeth: Advisory Board Johnson & Johnson. Received medical writing assistance funded by Johnson & Johnson. Russell, Richard K.: Grant: Nestec Other: Abbvie, Celltrion, Janssen, Lilly, Nestle, Pharmacosmos, Pfizer 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, Gentech Research support: Janssen, Abbvie, Takeda, Pfizer Received medical writing assistance funded by Johnson & Johnson Royalties: Shaare Zedek Medical Center, Hospital for Sick Children Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda Received medical writing assistance funded by Johnson & Johnson Hyams, Jeffrey: Abbvie: Advisory Board Janssen: Advisory Board Roche/Genentech: Consultant Received medical writing assistance funded by Johnson & Johnson Takeda: Consultant Cohen, Stanley: Consultant: Janssen, Kate Farms Research grants last 3 years: Janssen, Abbvie Principal: Nutrition4Kids, LLC Received medical writing assistance funded by Johnson & Johnson Rosh, Joel: Advisor/Consultant: AbbVie, Janssen, Mesoblast. 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 Strauss, Richard: Employee of Johnson & Johnson and may own/have 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. Conklin, Laurie: I am an employee of Johnson and Johnson and I hold stock options in the company. Received medical writing assistance funded by Johnson & Johnson. Adedokun, Omoniyi: Employee Johnson & Johnson and may own/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: Work for 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.