J Pediatr Gastroenterol Nutr. 2022 Dec 1;75(6):717-723.doi: 10.1097/MPG.0000000000003608. Epub 2022 Sep 8.

Anat Yerushalmy-Feler ¹, Gemma Pujol-Muncunill ², Javier Martin-de-Carpi ², Kaija-Leena Kolho ³, Arie Levine ⁴, Christine Olbjørn ⁵, Maya Granot ^6 7, Matteo Bramuzzo ⁸, Helena Rolandsdotter ⁹, Natalia Mouratidou ¹⁰, Ondrej Hradsky ¹¹, Luca Scarallo ¹², Manar Matar ¹³, Ramit Magen Rimon ¹⁴, Firas Rinawi ¹⁵, Tzippi Shalem ¹⁶, Hisham Najajra ¹⁷, Tim de Meij ¹⁸, Marina Aloi ¹⁹, Marta Velasco Rodríguez-Belvís ²⁰, Patrizia Alvisi ²¹, Anna-Maria Schneider ²², Patrick van Rheenen ²³, Víctor Manuel Navas-López ²⁴, Fevronia Kiparissi ²⁵, Josefa Barrio ²⁶, Dan Turner ²⁷, Shlomi Cohen ¹

Author information

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

²the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.

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

⁴the Pediatric Gastroenterology Unit, PIBD Research Center, Wolfson Medical Center, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

⁵the Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.

⁶the Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

⁷the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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

⁹the Department of Clinical Science and Education, Karolinska Institute, and Department of Gastroenterology, Sachs' Children and Youth Hospital, Stockholm, Sweden.

¹⁰the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden.

¹¹the Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.

¹²the Gastroenterology and Nutrition Unit, Meyer Children's Hospital, Florence, Italy.

¹³the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

¹⁴the Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, The Technion, Haifa, Israel.

¹⁵the Paediatric Gastroenterology Unit, Ha'Emek Medical Centre, Afula, Faculty of Medicine, The Technion, Haifa, Israel.

¹⁶the The Jecheskiel Sigi Gonczarowski Pediatric Gastroenterology Unit, Shamir Medical Center, Zerifin, Israel.

¹⁷The Juliet Keiden Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel.

¹⁸the Department of Pediatric Gastroenterology, Amsterdam University Medical Centre, Amsterdam, the Netherlands.

¹⁹the Department of Maternal and Child Health, Pediatric Gastroenterology and Liver Unit, Umberto I Hospital, Sapienza University of Rome, Rome, Italy.

²⁰the Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Niño Jesús, Madrid, Spain.

²¹the Pediatric Gastroenterology Unit, Department of Pediatrics, Maggiore Hospital, Bologna, Italy.

²²the Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.

²³the Paediatric Gastroenterology, University Medical Centre Groningen Beatrix Childrens Hospital, Groningen, the Netherlands.

²⁴the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain.

²⁵the Department of Pediatric Gastroenterology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, United Kingdom.

²⁶the Department of Paediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain.

²⁷the The Juliet Keiden Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, and the Hebrew University of Jerusalem, Jerusalem, Israel.

Abstract

Objectives: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD.

Methods: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up.

Results: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported.

Conclusions: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.