Management of Paediatric Patients With Medically Refractory Crohn’s Disease Using Ustekinumab: A Multi-Centred Cohort Study

Chavannes, Mallory; Martinez-Vinson, Christine; Hart, Lara; Kaniki, Nicole; Chen, Chao; Lawrence, Sally; Jacobson, Kevan; Hugot, Jean‐Pierre; Viala, Jérôme; Deslandres, Colette; Jantchou, P; Seidman, Ernest G.

doi:10.1093/ecco-jcc/jjy206

Cited by 50 publications

(79 citation statements)

References 31 publications

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“…16 Most recently, a multi-center cohort study examined 44 pediatric CD patients retrospectively, finding that at 12 months, 38.6% achieved clinical remission and 47.8% achieved clinical response. 18 Another recent study found that amongst 52 children with either CD or UC initiating ustekinumab, 50% of those previously exposed to anti-TNF treatment were in steroid-free remission by week 52. 19 Our results demonstrate the potential for mucosal healing in pediatric patients receiving ustekinumab.…”

Section: Discussionmentioning

confidence: 99%

“…Certain patients' medical charts were reviewed independently for another study (Chavannes et al). 18 In the cases of these patients, the overlap predominantly consists of baseline data, with the current study including additional outcome variables and longer follow-up. This study was approved by the Research Ethics Board of the McGill University Health Centre (approval No.…”

Section: Methodsmentioning

confidence: 99%

“…[9][10][11][12][13][14][15] At present, limited data exists on ustekinumab use in pediatric CD, showing variable results. [16][17][18][19][20] We retrospectively describe 11 adolescent patients who received ustekinumab at the Montreal Children' s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission.…”

Section: Introductionmentioning

confidence: 99%

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Ustekinumab for the treatment of refractory pediatric Crohn’s disease: a single-center experience

2021

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such as infliximab and adalimumab, some patients need a change in therapy due to allergic reactions, adverse events, as well as primary and secondary loss of response, highlighting the necessity for therapies acting by different mechanisms. 5 Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin-12 and interleukin-23, has been approved to treat adults with active psoriatic arthritis or moderately to severely active CD, as well as to treat both adults and children aged 12 or older with moderate to severe plaque psoriasis. 6 Thus far, in the adult CD population, ustekinumab has demonstrated variable clinical response rates ranging from under 40% to as high as 84%. 7,8 When successful, it has been shown

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ustekinumab for the treatment of refractory pediatric Crohn’s disease: a single-center experience

2021

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“…Chavannes et al [13] reported that 21 (48%) of 44 pediatric patients who had been intolerant CD to at least one biologics showed an initial response, and 8 (39%) of them achieved prolonged clinical remission by subcutaneous ustekinumab. Clinical remission rate of adult patients naïve to anti-TNF antibody reached about 70% after ustekinumab therapy [12,13]. By contrast, the remission rates of anti-TNF antibody as the first biologics for adult patients with CD ranged from 40 to 70%.…”

Section: Discussionmentioning

confidence: 99%

“…The major concern is a risk of prolonged biologics therapy for children. Several clinical trials [11,13] reported the long-term remission, low immunogenicity rates and low incident of adverse events in ustekinumab therapy, 8 suggesting a favorable choice of ustekinumab for pediatric-onset CD. It is preferred for patients with the history of psoriasis or demyelinating diseases including multiple sclerosis and optic neuritis because anti-TNF antibody has a risk of exacerbation in such underlying diseases [10].…”

Section: Discussionmentioning

confidence: 99%

Ustekinumab therapy and serum IL-12/IL-23p40 levels for biologic naïve pediatric-onset Crohn disease

Shiraishi

Ishimura

Eguchi

et al. 2019

Preprint

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Background: The treatment effect of ustekinumab for Crohn disease (CD) that is refractory to tumor necrosis factor (TNF)-α blockers has been approved in adults, but the indication for pediatric cases remains elusive. The present study aimed to assess the applicability of ustekinumab therapy for biologic naïve pediatric patients.Methods: Four patients who developed CD until 15 years of age and then came to receive ustekinumab as the first-line biologic therapy were enrolled. Clinical and laboratory findings, treatment history, outcomes and adverse events of the biologics were retrospectively studied by using the medical records and interviews to attending doctors. To evaluate the inflammatory profiles at the time of starting ustekinumab, serum concentrations of interleukin (IL)-12/IL-23p40, TNF-α, IL-1β, IL-6, IL-8 and IL-10 were measured by the enzyme-linked immunosorbent or immunobead assays. Results: All patients underwent ustekinumab therapy because of the refractory or relapsing disease on conventional therapy and the individual reasons including optic neuritis. Three out of four patients obtained complete remission followed by successful maintenance, although one failed. No adverse events occurred at all. Pretreatment IL-12/IL-23p40 levels of all three responders, but not one non-responder or healthy controls, exceeded 80 pg/ml. On the other hand, the other cytokine levels of all patients were indifferently negligible. Conclusions: Ustekinumab was effectively used as one of the first-line biologics for the treatment of pediatric-onset CD. The limited indication to anti-TNF therapies or the elevated levels of serum IL-12/IL-23p40 may be a preferable choice of the treatment in childhood.

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Efficacy of infliximab after loss of response of/intolerance to adalimumab in pediatric Crohn's disease: A retrospective multicenter cohort study of the “GETAID pédiatrique”

Lecoutour,

Dupont,

Caldari

et al. 2024

J. pediatr. gastroenterol. nutr.

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BackgroundInfliximab (IFX) and adalimumab (ADA) are recommended for induction and maintenance of remission in pediatric Crohn's disease (CD). ADA is now often used in first line due to its efficacy and tolerability, but a loss of response (LOR) can occur over time. The aim was to assess the efficacy of IFX as second line therapy after LOR or intolerance to ADA in pediatric CD patients at 1 year.MethodsWe conducted a retrospective and multicenter study in France among the “GETAID pédiatrique” centers between April 2019 and April 2022. CD patients under 18 years old and treated with IFX after ADA failure or intolerance were included. We collected anthropometric, clinical, and biological data at baseline (start of IFX), at 6 and 12 months. Clinical remission was defined by a Weighted Pediatric CD Activity Index (wPCDAI) score less than 12.5 points.ResultsOf the 32 patients included in our study, 27 (84.4%) were still on IFX at 12 months of the switch. Among them, 13 had discontinued ADA because of a LOR, 12 for insufficient response and 2 due to primary nonresponse. At M12, 22 patients were in corticosteroid free clinical remission (68.7%). Under IFX, the wPCDAI decreased over time (47.5 ± 24.1, 16.6 ± 21.2 and 9.7 ± 19.0 at M0, M6 and M12 respectively). The only factor associated with clinical remission at 12 months was absence of perianal disease at the end of the IFX induction.ConclusionsIFX is effective in maintaining remission at 1 year in pediatric CD patients experiencing a LOR or intolerance with ADA, and IFX could be an interesting therapeutic choice instead of other biologics in this situation.

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Management of Paediatric Patients With Medically Refractory Crohn’s Disease Using Ustekinumab: A Multi-Centred Cohort Study

Cited by 50 publications

References 31 publications

Ustekinumab for the treatment of refractory pediatric Crohn’s disease: a single-center experience

Ustekinumab for the treatment of refractory pediatric Crohn’s disease: a single-center experience

Ustekinumab therapy and serum IL-12/IL-23p40 levels for biologic naïve pediatric-onset Crohn disease

Efficacy of infliximab after loss of response of/intolerance to adalimumab in pediatric Crohn's disease: A retrospective multicenter cohort study of the “GETAID pédiatrique”

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