Elisabeth De Greef, Dan Turner, Jarosław Kierkuś, Bartosz Korczowski, Monika Meglicka, Stanley A. Cohen, Jeffrey S Hyams, Anne M Griffiths, J Rosh, Richard S Strauss, Els Van Limbergen, O Adedokun, Lilianne Kim, S Volger, for the UNITI Jr study Group, Pauline De Bruyne, Patrick Bontems, Ilse Hoffman, Françoise Smets, Sibylle Koletzo, Philip Bufler, Lena Woelfle, Tobias Wenzl, Ulrich Baumann, Denisa Pilic, Michael Melter, Orsolya Kadenczki, Csaba Bereczki, Antal Dezsőfi, F. Dicső, Erzsébet Szakos, Yigal Elenberg-Alter, Dror Shouval, Efrat Broide, Katsuhiro Arai, Takahiro Kudo, Takashi Ishige, Itaru Iwama, Tatsuki Mizuochi, Daiki Abukawa, Yuhki Koike, Hideki Kumagai, Sotaro Mushiake, Kinga Kowalska-Duplaga Piotr Landowski, Aelita Kamalova, Vladimir Kopeikin, Elena Sitnikova, Ekaterina Tsimbalova, Richard Russell, Sandhia Naik, Franco Torrente, Rafeeq Muhammed, Christine Spray, Michael Stephens, Tamara L Feldman, Zarela Molle-Rios, Tiffany Linville, Thomas J. Sferra, Jeffrey D. Lewis, Otto Louis-Jacques, Marc Schaefer, B. O. Osuntokun, Bess Aramakis, Harold Couchoux, Kordian Von Cyga, Laurie S. Conklin, Bridget Godwin, Katarzyna Cieślak, Auguste Gaddah, Renping Zhang, Li Deng, Wouter Van der Borght, Esau Moreno Carmache
BACKGROUND: UNITI Jr is a phase 3 study evaluating the efficacy, safety, and pharmacokinetics of ustekinumab, an interleukin-12/-23 antagonist, in pediatric patients with moderately to severely active Crohn's disease. Results from patients weighing at least 40 kg are reported. METHODS: Patients at least 40 kg and aged less than 18 years with a Pediatric Crohn's Disease Activity Index score of >30 received a single intravenous weight-tiered induction dose of ustekinumab. After 8 weeks, patients were randomized to subcutaneous ustekinumab 90 mg every 8 or 12 weeks. The primary endpoint was clinical remission at Week 8. Secondary endpoints included clinical response (Weeks 8, 52), endoscopic response (Weeks 16, 52), clinical remission, and corticosteroid-free remission (Week 52). RESULTS: Of 48 patients, median age was 15.0 years (interquartile range: 14.0-16.0). At Week 8, 52.1% (25/48) achieved clinical remission and 93.8% (45/48) achieved clinical response. At Week 16, 29.8% (14/47) achieved endoscopic response. Clinical remission at Week 52 was achieved in 15/25 (60.0%; every 12 weeks) and 10/23 (43.5%; every 8 weeks). Three patients (6.3%) discontinued ustekinumab between Weeks 8 and 52. Ustekinumab was safe and well-tolerated; adverse event rates were similar between groups. Immunogenicity was low; trough median (mean) steady-state serum ustekinumab concentrations following 8 weeks of dosing were 1.38 (2.08) to 1.74 (2.32) μg/mL and were comparable to levels in adult patients: 2.83 (2.05) μg/mL. CONCLUSIONS: Ustekinumab induction and maintenance therapy was effective and safe through 52 weeks in pediatric patients weighing at least 40 kg with moderately to severely active Crohn's disease. TRIAL REGISTRATION NUMBERS: NCT04673357.