Crohn's & colitis 360 · 2026
Early proactive therapeutic drug monitoring with ustekinumab therapy in pediatric Crohn's disease: data from the prospective Canadian children IBD network.
СтатьяНазвание и аннотация: Перевод в очереди
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Ricciuto Amanda, McKay Hayley E, deBruyn Jennifer C, Crowley Eileen, Church Peter C, Huynh Hien Q, Otley Anthony R, Shaikh Ayub, Mack David R, Carman Nicholas, El-Matary Wael, Schneider Rilla, Wine Eytan, Walters Thomas D, Griffiths Anne M, Canadian Children IBD Network
Аннотация
BACKGROUND: Ustekinumab dosing information for pediatric Crohn's disease (CD) is limited.
AIMS: To examine ustekinumab pharmacokinetic and effectiveness data in a largely bio-naïve cohort, focusing on early (week 8) levels.
METHODS: Children in the prospective Canadian Children IBD Network initiating intravenous (IV) ustekinumab for CD with a week 8 level were evaluated. Disease activity was assessed by corticosteroid-free clinical remission (CSFR), biochemical CSFR, and mucosal healing (MH) by colonoscopy or fecal calprotectin <150 µg/g beyond 16 weeks. We compared drug levels by weight group (</≥40kg) and outcome, using receiver-operating characteristic (ROC) curves to identify optimal week 8 levels.
RESULTS: Amongst 58 children (19 < 40 kg, 81% bio-naïve, median (interquartile range [IQR]) follow-up 11.5 [7.6-16.0] months), the IV loading dose for those <40kg (median 9.1 [8.6-10.2] mg/kg; 253 (239-268) mg/m2) was greater than for those ≥40kg (median 6.1 [5.4-6.5] mg/kg; 218 ([78-237] mg/m2, P < .001). However, week 8 levels were similar (P = .26). This was most striking in those with low albumin. Of 34/58 (59%) without escalation to 4 weekly dosing, 43%, 35%, and 19% exhibited CSFR, biochemical CSFR, and MH, respectively, during established maintenance. Median week 8 levels were roughly 5-6 µg/g vs 7-10 µg/g in patients not achieving vs achieving favorable outcomes, while ROC analysis indicated levels 8-9 µg/mL were associated with improved outcomes.
CONCLUSIONS: Children <40 kg required more IV ustekinumab (median 9 mg/kg; 250 mg/m2) to achieve similar week 8 levels as children ≥40kg receiving conventional adult 6 mg/kg weight-tiered induction. Higher week 8 levels were associated with favorable later outcomes.
AIMS: To examine ustekinumab pharmacokinetic and effectiveness data in a largely bio-naïve cohort, focusing on early (week 8) levels.
METHODS: Children in the prospective Canadian Children IBD Network initiating intravenous (IV) ustekinumab for CD with a week 8 level were evaluated. Disease activity was assessed by corticosteroid-free clinical remission (CSFR), biochemical CSFR, and mucosal healing (MH) by colonoscopy or fecal calprotectin <150 µg/g beyond 16 weeks. We compared drug levels by weight group (</≥40kg) and outcome, using receiver-operating characteristic (ROC) curves to identify optimal week 8 levels.
RESULTS: Amongst 58 children (19 < 40 kg, 81% bio-naïve, median (interquartile range [IQR]) follow-up 11.5 [7.6-16.0] months), the IV loading dose for those <40kg (median 9.1 [8.6-10.2] mg/kg; 253 (239-268) mg/m2) was greater than for those ≥40kg (median 6.1 [5.4-6.5] mg/kg; 218 ([78-237] mg/m2, P < .001). However, week 8 levels were similar (P = .26). This was most striking in those with low albumin. Of 34/58 (59%) without escalation to 4 weekly dosing, 43%, 35%, and 19% exhibited CSFR, biochemical CSFR, and MH, respectively, during established maintenance. Median week 8 levels were roughly 5-6 µg/g vs 7-10 µg/g in patients not achieving vs achieving favorable outcomes, while ROC analysis indicated levels 8-9 µg/mL were associated with improved outcomes.
CONCLUSIONS: Children <40 kg required more IV ustekinumab (median 9 mg/kg; 250 mg/m2) to achieve similar week 8 levels as children ≥40kg receiving conventional adult 6 mg/kg weight-tiered induction. Higher week 8 levels were associated with favorable later outcomes.