Paediatr Drugs. 2024 Sep;26(5):609-617.doi: 10.1007/s40272-024-00631-z. Epub 2024 May 23.

Shlomi Cohen ¹, Helena Rolandsdotter ^2 3, Kaija-Leena Kolho ^4 5, Dan Turner ⁶, Christos Tzivinikos ⁷, Matteo Bramuzzo ⁸, Gemma Pujol-Muncunill ⁹, Luca Scarallo ¹⁰, Darja Urlep ¹¹, Firas Rinawi ^12 13, Maya Granot ^14 15, Ben Kang ¹⁶, Ylva Longueville ¹⁷, Marta Velasco Rodríguez-Belvís ¹⁸, Yael Weintraub ¹⁹, Víctor Manuel Navas-López ²⁰, Anat Yerushalmy-Feler ²¹

Author information

¹Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel. shlomico@tlvmc.gov.il.

²Department of Clinical Science and Education and Department of Gastroenterology, Sachs Children and Youth Hospital, Karolinska Institute, Stockholm, Sweden.

³Department of Gastroenterology, Sachs' Children and Youth Hospital, Stockholm, Sweden.

⁴Department of Paediatric Gastroenterology, Children's Hospital and Tampere University, HUS and University of Helsinki, Helsinki, Finland.

⁵Tampere University, Tampere, Finland.

⁶The Juliet Keiden Institute of Pediatric Gastroenterology and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

⁷Department of Pediatric Gastroenterology, Al Jalila Children's Specialty Hospital, Mohamed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.

⁸Gastroenterology, Digestive Endoscopy and Nutrition Unit, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.

⁹Department of Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.

¹⁰Gastroenterology and Nutrition Unit, Meyer Children's Hospital IRCCS, Florence, Italy.

¹¹Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, 1000, Ljubljana, Slovenia.

¹²Pediatric Gastroenterology Unit and Faculty of Medicine Technion, Haifa, Emek Medical Centre, Afula, Israel.

¹³Faculty of Medicine Technion, Haifa, Israel.

¹⁴Pediatric Gastroenterology and nutrition Unit, Edmond and Lily Safra Children's Hospital and the Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Ramat Gan, Israel.

¹⁵The Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

¹⁶Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

¹⁷Pediatric Gastroenterology Unit, Karolinska University Hospital, Stockholm, Sweden.

¹⁸Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

¹⁹Schneider Children's Medical Center and the Faculty of Medicine, Institute of Gastroenterology, Nutrition and Liver Diseases, Tel Aviv University, Tel Aviv, Israel.

²⁰Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain.

²¹Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 6423906, Tel Aviv, Israel.

Abstract

Background and objectives: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU.

Methods: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle.

Results: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three.

Conclusion: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.