Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN

Anat Yerushalmy-Feler, Gemma Pujol-Muncunill, Javier Martin-De-Carpi, Kaija Leena Kolho, Arie Levine, Christine Olbjørn, Maya Granot, Matteo Bramuzzo, Helena Rolandsdotter, Natalia Mouratidou, Ondrej Hradsky, Luca Scarallo, Manar Matar, Ramit Magen Rimon, Firas Rinawi, Tzippi Shalem, Hisham Najajra, Tim De Meij, Marina Aloi, Marta Velasco Rodríguez-BelvísPatrizia Alvisi, Anna Maria Schneider, Patrick Van Rheenen, Víctor Manuel Navas-López, Fevronia Kiparissi, Josefa Barrio, Dan Turner, Shlomi Cohen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)717-723
Number of pages7
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume75
Issue number6
DOIs
StatePublished - 1 Dec 2022

Keywords

  • Crohn disease
  • biologics
  • children
  • ustekinumab

All Science Journal Classification (ASJC) codes

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health

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