Real World Experience With Ustekinumab in Children and Young Adults at a Tertiary Care Pediatric Inflammatory Bowel Disease Center

Dayan, Judy R; Dolinger, Michael; Benkov, Keith; Dunkin, David; Jossen, Jacqueline; Lai, Joanne; Phan, Becky L.; Pittman, Nanci; Dubinsky, Marla C.

doi:10.1097/mpg.0000000000002362

Cited by 89 publications

(85 citation statements)

References 22 publications

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“…UST is effective for treatment of Crohn's disease (CD) and ulcerative colitis 1‐4 . In addition to randomised controlled trials, multiple real‐world studies corroborated the effectiveness of UST in the treatment of CD 5‐19 . However, the risk of primary and secondary loss of response to UST has not been extensively reported.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

Kopylov¹,

Hanžel²,

Liefferinckx³

et al. 2020

Aliment Pharmacol Ther

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Summary Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited. Aim To assess the effectiveness of dose escalation of ustekinumab. Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

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Section: Introductionmentioning

confidence: 99%

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

Kopylov¹,

Hanžel²,

Liefferinckx³

et al. 2020

Aliment Pharmacol Ther

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“…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. Furthermore, while in the other pediatric studies, all patients received maintenance doses of ustekinumab every 7-8 weeks, doses in our study were shown to be given as frequently as every 4 weeks in an attempt to optimize therapy prior to labeling a patient as a nonresponder, with no adverse effects noted.…”

Section: Discussionmentioning

confidence: 51%

“…[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%

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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“…Ustekinumab fully human monoclonal antibody specifically binds to p40, common subunit of IL-12/IL-23, and neutralizes the bioactivity of IL-12/IL-23 which is closely associated with active IBD [15]. High concentrations of circulating ustekinumab by intravenous induction might effectively suppress IL-12/IL-23 pathway and lead to a prompt remission of responders [3,12].…”

Section: Discussionmentioning

confidence: 99%

“…Ustekinumab, human monoclonal antibody that binds with high affinity to interleukin (IL)-12/IL-23p40 subunit induces clinical remission of refractory adult cases via the inhibition of cytokine production and inflammation [2]. However, the effectiveness in childhood IBD has not been established [3], and the applicability for pediatric cases remains elusive. The first-line biologics for the early-onset IBD are challenging to determine because TNF-α blockers often occur in association with infections and immunological disorders [4].…”

Section: Introductionmentioning

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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Real World Experience With Ustekinumab in Children and Young Adults at a Tertiary Care Pediatric Inflammatory Bowel Disease Center

Cited by 89 publications

References 22 publications

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

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

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