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

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7603873 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1076 (Electronic) Linking ISSN: 03406199 NLM ISO Abbreviation: Eur J Pediatr Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer-Verlag.

Crohn Disease*/drug therapy ; Ustekinumab*/therapeutic use; Humans ; Male ; Female ; Retrospective Studies ; Adolescent ; Child ; Treatment Outcome ; Remission Induction ; Severity of Illness Index

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.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Argollo MC, Allocca M, Furfaro F, Peyrin-Biroulet L, Danese S (2019) Interleukin-23 blockers: born to be first-line biologic agents in inflammatory bowel disease? Curr Pharm Des 25(1):25–31. (PMID: 31092171)
Hanauer SB, Sandborn WJ, Feagan BG, Gasink C, Jacobstein D, Zou B et al (2020) IM-UNITI: three-year efficacy, safety, and immunogenicity of ustekinumab treatment of Crohn’s disease. J Crohns Colitis 14(1):23–32. (PMID: 31158271)
Sands BE, Sandborn WJ, Panaccione R, O’Brien CD, Zhang H, Johanns J et al (2019) Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 381(13):1201–1214. (PMID: 31553833)
Bishop C, Simon H, Suskind D, Lee D, Wahbeh G (2016) Ustekinumab in pediatric Crohn disease patients. J Pediatr Gastroenterol Nutr 63(3):348–351. (PMID: 26854655)
Cameron FL, Garrick V, Russell RK (2016) Ustekinumab in treatment of refractory paediatric Crohn disease. J Pediatr Gastroenterol Nutr 62(3):e30. (PMID: 26910458)
Rinawi F, Rosenbach Y, Assa A, Shamir R (2016) Ustekinumab for resistant pediatric Crohn disease. J Pediatr Gastroenterol Nutr 62(4):e34–e35. (PMID: 25023579)
Fusillo SJ, Chang V, Stein RE, Maxwell EC, Conrad MA, Albenberg L et al (2018) 329 - Ustekinumab responders versus non-responders in refractory pediatric inflammatory bowel disease. Gastroenterology 154(6):S–82.
Chavannes M, Martinez-Vinson C, Hart L, Kaniki N, Chao CY, Lawrence S et al (2019) Management of paediatric patients with medically refractory Crohn’s disease using ustekinumab: a multi-centred cohort study. J Crohns Colitis 13(5):578–584. (PMID: 30541021)
Dayan JR, Dolinger M, Benkov K, Dunkin D, Jossen J, Lai J et al (2019) Real world experience with ustekinumab in children and young adults at a tertiary care pediatric inflammatory bowel disease center. J Pediatr Gastroenterol Nutr 69(1):61–67. (PMID: 310587187408448)
Do P, Andersen J, Patel A, Semrin G, Sifuentes-Dominguez L, Luu P et al (2021) Augmented ustekinumab dosing is needed to achieve clinical response in patients with anti-TNF refractory pediatric Crohn’s disease: a retrospective chart review. F1000Research 9:316. (PMID: 8408544)
Dolinger MT, Spencer EA, Lai J, Dunkin D, Dubinsky MC (2021) Dual biologic and small molecule therapy for the treatment of refractory pediatric inflammatory bowel disease. Inflamm Bowel Dis 27(8):1210–1214. (PMID: 33125058)
Kim FS, Patel PV, Stekol E, Ali S, Hamandi H, Heyman MB et al (2021) Experience using ustekinumab in pediatric patients with medically refractory Crohn disease. J Pediatr Gastroenterol Nutr 73(5):610–614. (PMID: 344157118542638)
Koudsi M, Martinez-Vinson C, Pigneur B, Willot S, Djamal D, Enaud R et al (2023) Ustekinumab use in pediatric inflammatory bowel disease: a French multicenter study from the pediatric GETAID. J Pediatr Gastroenterol Nutr 76(6):763–770. (PMID: 36893481)
Rosh JR, Turner D, Griffiths A, Cohen SA, Jacobstein D, Adedokun OJ et al (2021) Ustekinumab in paediatric patients with moderately to severely active Crohn’s disease: pharmacokinetics, safety, and efficacy results from UniStar, a Phase 1 study. J Crohns Colitis 15(11):1931–1942. (PMID: 340377158575045)
Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, Griffiths AM et al (2021) STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 160(5):1570–1583. (PMID: 33359090)
Yerushalmy-Feler A, Pujol-Muncunill G, Martin-de-Carpi J, Kolho KL, Levine A, Olbjørn C et al (2022) 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. J Pediatr Gastroenterol Nutr 75(6):717–723. (PMID: 36084231)
Takeuchi I, Arai K, Kyodo R, Sato T, Tokita K, Hirano Y et al (2021) Ustekinumab for children and adolescents with inflammatory bowel disease at a tertiary children’s hospital in Japan. J Gastroenterol Hepatol 36(1):125–130. (PMID: 32497325)
Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L et al (2014) ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 58(6):795–806. (PMID: 24231644)
Turner D, Levine A, Walters TD, Focht G, Otley A, Lopez VN et al (2017) Which PCDAI version best reflects intestinal inflammation in pediatric Crohn disease? J Pediatr Gastroenterol Nutr 64(2):254–260. (PMID: 27050050)
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42(2):377–381. (PMID: 18929686)
Van Rheenen PF, Aloi M, Assa A, Bronsky J, Escher JC, Fagerberg UL et al (2021) The medical management of paediatric Crohn’s disease: an ECCO-ESPGHAN guideline update. J Crohns Colitis 15(2):171–194.
Fang S, Zhang S, Zhang C, Wang L (2023) Effectiveness and safety of ustekinumab for pediatric inflammatory bowel disease: a systematic review. Pediatr Drugs 25(5):499–513.
Cohen A, Ahmed N, Sant’Anna A, (2021) Ustekinumab for the treatment of refractory pediatric Crohn’s disease: a single-center experience. Intest Res 19(2):217–24. (PMID: 32312033)
Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR et al (2016) Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 375(20):1946–1960. (PMID: 27959607)
Ma C, Fedorak RN, Kaplan GG, Dieleman LA, Devlin SM, Stern N et al (2017) Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn’s disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther 45(9):1232–1243. (PMID: 28252210)
Harris KA, Horst S, Gadani A, Nohl A, Annis K, Duley C et al (2016) Patients with refractory Crohn’s disease successfully treated with ustekinumab. Inflamm Bowel Dis 22(2):397–401. (PMID: 26752468)
Alric H, Amiot A, Kirchgesner J, Tréton X, Allez M, Bouhnik Y et al (2020) The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn’s disease refractory to anti-tumour necrosis factor. Aliment Pharmacol Ther 51(10):948–957. (PMID: 32249966)
Greenup AJ, Rosenfeld G, Bressler B (2017) Ustekinumab use in Crohn’s disease: a Canadian tertiary care centre experience. Scand J Gastroenterol 52(12):1354–1359. (PMID: 28885058)
Penagini F, Lonoce L, Abbattista L, Silvera V, Rendo G, Cococcioni L et al (2023) Dual biological therapy and small molecules in pediatric inflammatory bowel disease. Pharmacol Res 196:106935. (PMID: 37748559)

Keywords: Children; Crohn’s disease; Exclusive enteral nutrition; Ustekinumab; wPCDAI

FU77B4U5Z0 (Ustekinumab)

Pediatric Crohn's disease

Date Created: 20240503 Date Completed: 20240722 Latest Revision: 20240913

20240914

10.1007/s00431-024-05588-2

38700692