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STEP-CD study: ustekinumab use in paediatric Crohn’s disease—a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN

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Abstract

Ustekinumab is an effective therapy for adult Crohn’s disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn’s Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7–17.2) with a median follow-up of 7.4 months (IQR 5.6–11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25–57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.

   Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD.

What is Known:

• Ustekinumab is an effective therapy for adult moderate to severe Crohn’s disease (CD).

• Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD.

What is New:

• Is the largest cohort of real-world use of ustekinumab in paediatric CD to date.

• Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

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Data availability

No datasets were generated or analyzed during the current study.

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Author information

Authors and Affiliations

  1. Hospital Sant Joan de Déu, Barcelona, Spain

    Gemma Pujol-Muncunill & Javier Martin-de-Carpi

  2. Department of Paediatric Gastroenterology and Nutrition, Hospital Regional Universitario de Málaga, Málaga, Spain

    Víctor Manuel Navas-López

  3. Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel

    Oren Ledder, Marina Lekar, Dan Turner & Amit Assa

  4. Children’s Hospital Tel Aviv Sourasky Medical, Tel Aviv, Israel

    Shlomi Cohen

  5. Faculty of Medicine, University of Helsinki and Children’s Hospital, University of Helsinki and HUS, Helsinki, Finland

    Kaija-Leena Kolho

  6. Wolfson Medical Center, Holon, Israel

    Arie Levine

  7. The Royal London Children’s Hospital, Barts Health NHS Trust, London, UK

    Nicholas M. Croft & Sandhia Naik

  8. University Hospital Motol, Prague, Czech Republic

    Jiri Bronsky & Ondrej Hradsky

  9. Sheba Medical Center, Tel Hashomer, Israel

    Dror S. Shouval

  10. Royal Hospital for Children, Glasgow, UK

    Rachel Harris

  11. Great Ormond Street Hospital, London, UK

    Fevronia Kiparissi & Lucia Cococcioni

  12. Sapienza University of Rome, Rome, Italy

    Marina Aloi

  13. Southampton Children’s Hospital, Southampton, UK

    Nadeem Ahmad Afzal

  14. Al Jalila Children’s Speciality Hospital, Dubai, United Arab Emirates

    Christos Tzivinikos

  15. Hospital Universitario de Fuenlabrada, Madrid, Spain

    Josefa Barrio

  16. Hvidovre University Hospital, Copenhagen, Denmark

    Christoph Norden

  17. Hospital Virgen de La Macarena, Seville, Spain

    Maria Jesús Balboa Vega

  18. GFO-Kliniken Bonn St. Marien-Hospital, Bonn, Germany

    Stephan Buderus

  19. Hospital Universitario de Burgos, Burgos, Spain

    Ana Fernández de Valderrama

  20. Erasmus Medical Center Sophia Children’s Hospital, Rotterdam, Netherlands

    Lissy de Ridder

  21. Hospital Universitario Miguel Servet, Saragossa, Spain

    Ruth García-Romero

  22. Hospital, 12 de Octubre, Madrid, Spain

    Enrique Medina

  23. Hospital Gregorio Marañón, Madrid, Spain

    César Sánchez

  24. Hospital Universitario Niño Jesús, Madrid, Spain

    Marta Velasco

  25. Hospital Universitario Ramon y Cajal, Madrid, Spain

    Saioa Vicente

  26. Child Life and Health, University of Edinburgh, Edinburgh, UK

    David C. Wilson

Authors
  1. Gemma Pujol-Muncunill
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  2. Víctor Manuel Navas-López
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  3. Oren Ledder
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  4. Shlomi Cohen
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  5. Marina Lekar
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  15. Marina Aloi
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  30. Sandhia Naik
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  32. Lucia Cococcioni
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  33. Javier Martin-de-Carpi
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Contributions

GPM, JMC and VMNL designed the data collection instruments, coordinated and supervised data collection, conducted the analyses, drafted the initial manuscript and reviewed and edited the manuscript.VMN-L, JM, GP, JD and RM-M conducted the analyses, drafted the initial manuscript and reviewed and edited the manuscript. All authors reviewed and edited the manuscript and approved the final manuscript as submitted and agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Víctor Manuel Navas-López.

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Competing interest

GPM: speakers fees and congress support from Abbvie, Nestlé Health Science, Janssen. VNL: consultant fees from Abbvie, Nestlé Health Science, Otsuka, Pfizer. DT: consultant fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, BMS. KLK: consultant fees from Abbvie, Biocodex, Ferring, Tillots Pharma, MSD. AL: Nestlé Health Science, Janssen, Abbvie, Takeda and Megapharm. JB: honoraria, speakers fees and congress support from Abbvie, MSD, Nestlé Health Science, Nutricia, Biocodex, Ferring and Walmark. AA: consultant and lectures fees from Abbvie. Research grants from Abbvie and Janssen. FK: educational Grant from Dr. Falk, Abbvie. DCW: honoraria, speakers fees and/or congress support from Abbvie, Nestlé Health Science, Ferring, Roche, and Predictimmune. Abbvie and Janssen. LC: educational Grant from Dr. Falk. LR: Shire, Malinckrodt, Nestlé, Celltrion, Abbvie, Pfizer. Grant from ZonMw, ECCO and Pfizer. JMC: consultation fees, research grants, or honoraria from Abbvie, MSD, Janssen, Adacyte, Otsuka, Celltrion, Roche, Celgene, Dr. Falk, Nestlé HS, Ferring, FAES, Kern Pharma. The remaining authors have no competing interest.

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Pujol-Muncunill, G., Navas-López, V.M., Ledder, O. et al. STEP-CD study: ustekinumab use in paediatric Crohn’s disease—a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05588-2

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