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Multicenter Study
. 2022 Dec 1;75(6):717-723.
doi: 10.1097/MPG.0000000000003608. Epub 2022 Sep 8.

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  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
Affiliations
Multicenter Study

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 et al. J Pediatr Gastroenterol Nutr. .

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.

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Conflict of interest statement

GPM has received speakers fees and congress support from Abbvie, Nestlé Health Science, Janssen and Nutricia. KLK has received consultancy fees from Abbvie, Biocodex, Ferring and Tillotts Pharma and funding for research from Pediatric Research Foundation and Helsinki University Hospital Research Fund. OH reports lectures/congress fees/consultancy (outside the submitted work): MSD, AbbVie, Takeda, Nutricia, Nestlé and Ferring. OH reports lectures/congress fees/consultancy (outside the submitted work): MSD, AbbVie, Takeda, Nutricia, Nestlé and Ferring. The remaining authors report no conflicts of interest.

References

    1. Feagan BG, Sandborn WJ, Gasink C, et al. UNITI–IM-UNITI Study Group. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375:1946–60.
    1. Hanauer SB, Sandborn WJ, Feagan BG, et al. IM-UNITI: three-year efficacy, safety, and immunogenicity of ustekinumab treatment of Crohn’s disease. J Crohns Colitis. 2020;14:23–32.
    1. Sands BE, Sandborn WJ, Panaccione R, et al.; UNIFI Study Group. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381:1201–14.
    1. Panaccione R, Danese S, Sandborn WJ, et al. Ustekinumab is effective and safe for ulcerative colitis through 2 years of maintenance therapy. Aliment Pharmacol Ther. 2020;52:1658–75.
    1. Rutgeerts P, Gasink C, Chan D, et al. Efficacy of ustekinumab for inducing endoscopic healing in patients with Crohn’s disease. Gastroenterology. 2018;155:1045–58.

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