Inflamm Bowel Dis. 2023 Apr 12;izad064. doi: 10.1093/ibd/izad064. Online ahead of print.

Anat Yerushalmy-Feler ¹, Christine Olbjorn ², Kaija-Leena Kolho ^3 4, Marina Aloi ⁵, Francesca Musto ⁵, Javier Martin-de-Carpi ⁶, Ana Lozano-Ruf ⁶, Dotan Yogev ⁷, Manar Matar ⁸, Luca Scarallo ⁹, Matteo Bramuzzo ¹⁰, Lissy de Ridder ¹¹, Ben Kang ¹², Christoph Norden ¹³, David C Wilson ¹⁴, Christos Tzivinikos ¹⁵, Dan Turner ⁷, Shlomi Cohen ¹

Author information

¹Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

²Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.

³Department of Paediatric Gastroenterology, Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

⁴Tampere University, Tampere, Finland.

⁵Department of Maternal and Child Health, Pediatric Gastroenterology and Liver Unit, Umberto I Hospital, Sapienza University of Rome, Rome, Italy.

⁶Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.

⁷Juliet Keiden Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

⁸Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

⁹Gastroenterology and Nutrition Unit, Meyer Children's Hospital, Florence, Italy.

¹⁰Gastroenterology, Digestive Endoscopy and Nutrition Unit, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.

¹¹Department of Paediatric Gastroenterology, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands.

¹²Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

¹³Paediatric Department, Copenhagen University Hospital, Hvidovre, Denmark.

¹⁴Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, United Kingdom.

¹⁵Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.

Abstract

Background: Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD).

Methods: A retrospective study from 14 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded.

Results: Sixty-two children (35 Crohn's disease, 27 ulcerative colitis; median age 15.5 [interquartile range, 13.1-16.8] years) were included. They had all failed previous biologic therapies, and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to <250 µg/g were achieved in 75% and 64%, respectively, at 12 months of follow-up. Twenty-nine (47%) children sustained adverse events, 8 of which were regarded as serious and led to discontinuation of therapy in 6.

Conclusions: Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.