3 research outputs found
Vedolizumab Trough Levels in Children With Anti-Tumor Necrosis Factor Refractory Inflammatory Bowel Disease
Objectives: Inflammatory bowel disease (IBD) can be successfully treated
with vedolizumab. Studies in adult IBD patients have shown that differences in
response to vedolizumab may be related to variability in vedolizumab trough
levels, but in children with pediatric-onset IBD data regarding vedolizumab
trough levels are not available. Thus far, the role of trough levels in pediatriconset IBD treatment remains unclear. We aimed to investigate predictors of
vedolizumab trough levels in pediatric-onset IBD patients.
Methods: Data from anti-tumor necrosis factor refractory pediatric-onset IBD
patients who received vedolizumab were collected retrospectively. Vedolizumab
trough levels were measured in serum samples collected before each infusion. A
linear mixed model was conductedto analyze factorsthatinfluencetroughlevels.
Results: Twenty-six pediatric-onset IBD patients (14 ulcerative colitis [UC]),
9 Crohn Disease [CD], 3 IBD-unclassified [IBD-U]) received 258 vedolizumab
infusions. Mean vedolizumab trough level at week 6 was 29.9mg/mL (SD 17.8),
and 11.5 mg/mL (SD 4.9) during maintenance therapy. CD patients had
significantly lower trough levels than IBD-U patients (b 15.2; 95%
confidence interval [CI] 1.1 to 29.2; P¼ 0.036). Higher fecal calprotectin
(b 0.009; 95% CI 0.02 to 0.003; P¼ 0.007) and C-reactive protein levels
(b 0.4; 95% CI 0.72 to 0.04; P¼ 0.027) were associated with lower trough
levels, whereas shortening of time between infusions led to higher trough levels
(b 0.77; 95% CI 0.9 to 0.64; P< 0.001).
Conclusions: In this group of pediatric-onset IBD patients, trough levels
were significantly lower in CD patients compared with UC/IBD-
First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: An open-label multicentre randomised controlled trial
Objective: In newly diagnosed paediatric patients with moderate-to-severe Crohn's disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment. Design: In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3-17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis. Results: 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was no
Infliximab in young paediatric IBD patients: it is all about the dosing
Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years.What is Known?What is New