P671 Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: Results from the UniStar study long-term extension

Turner, D.(1)*;Rosh, J.R.(2);Cohen, S.A.(3);Griffiths, A.(4);Hyams, J.S.(5);Kierkuś, J.(6);Adedokun, O.J.(7);Strauss, R.(8);Kim, L.(9); Volger, S.(10);

(1)Shaare Zedek Medical Center- The Hebrew University of Jerusalem, The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, Jerusalem, Israel;(2)Goryeb Children’s Hospital/Atlantic Health, Pediatric Gastroenterology, Morristown- NJ, United States;(3)GI Care for Kids, Pediatric Gastroenterology, Atlanta- GA, United States;(4)The Hospital for Sick Children- University of Toronto, Pediatric Gastroenterology, Toronto- ON, Canada;(5)Connecticut Children’s Medical Center, Pediatric Gastroenterology, Hartford- CT, United States;(6)The Children’s Memorial Health Institute, Department of Gastroenterology- Hepatology- Feeding Disorders- and Paediatrics, Warsaw, Poland;(7)Janssen Research and Development- LLC, Clinical Pharmacology, Spring House- PA, United States;(8)Janssen Research and Development- LLC, Immunology, Horsham- PA, United States;(9)Janssen Research and Development- LLC, Biostatistics, Spring House- PA, United States;(10)Janssen Research and Development- LLC, Immunology, Spring House- PA, United States; UniStar Investigators


Ustekinumab (UST) is an approved biologic for the treatment of adults with Crohn’s disease (CD). Through 16 weeks (wks), UST demonstrated high rates of efficacy, low rates of immunogenicity, and safety in paediatric patients (pts) similar to that observed in adults.1 Here, we evaluated UST in paediatric CD pts through 268 wks.


UniStar was a phase 1, multicentre, double-blind study in paediatric pts (2-18 years old; body weight ≥10kg) with moderately to severely active CD. Pts (n=45) were randomised 1:1 and stratified by body weight (<40kg or ≥40kg) to low (3 mg/kg [<40kg]; 130 mg [≥40kg]) or high (9 mg/kg [<40kg]; 390 mg [≥40kg]) dose intravenous UST. At wk 8, pts received 1 subcutaneous maintenance dose (2 mg/kg [<40kg]; 90 mg [≥40kg]). Pts responding to UST at wk 16 were eligible to enter the long-term extension (LTE) and continued UST maintenance dosing every 8 wks up to wk 268. This study reports efficacy, safety, pharmacokinetics (PK), and immunogenicity evaluated at wks 16, 24, 48, 224, and through 240 wks, as applicable. The primary visit was wk 48, representing outcomes after ~1 year of UST treatment.


Of the 44 pts treated with UST, 34 (77%) responded and entered the LTE; the number of pts receiving treatment at wks 48, 104, 152, and 208 was 26 (77%), 16 (47%), 12 (35%), and 8 (24%), respectively. Among pts in the LTE (n=34), baseline median age (range) was 13.0 (6.0-17.0) years, 62% were female, 47% weighed <40kg, 18% weighed <30kg, and 94% previously failed anti-tumor necrosis factor therapy. At wk 48, 41% (14/34) of pts achieved clinical remission, and 59% (20/34) achieved clinical response. The proportion of pts with abnormal C-reactive protein (CRP) levels at baseline was 71% (24/34), and 59% (16/27) of pts achieved normalization of CRP (<3mg/L) at wk 48. By the final safety visit at wk 240, 91% of pts reported ≥1 adverse event (AE), and 15% discontinued due to AEs, with CD worsening as the most frequent reason. Infections occurred in 74% of pts, and 32% had serious AEs. The majority of serious AEs were gastrointestinal disorders associated with CD. No injection-site reactions, serious infections, malignancies, or deaths were reported. Median serum UST concentrations tended to be lower in pts weighing <40kg compared with pts weighing ≥40kg, but were generally consistent from wks 16 to 268 and remained detectable through wk 200 (Figure). Incidence of UST antibodies was low (1/34; 3%).


In the UniStar LTE, the efficacy, safety, PK, and immunogenicity of UST in paediatric pts with CD was generally consistent with adult pts for as long as 4 years of treatment.

Reference: 1. Rosh JR et al. J Crohns Colitis. 2021;15(11):1931.