High BMI affects anti-TNF response in paediatric Crohn’s disease


By Siobhan Calafiore

20 Mar 2024

Patients with paediatric Crohn’s disease and high BMI may require increased adalimumab dosing to achieve therapeutic trough levels, a study suggests.

Findings published in the American Journal of Gastroenterology [link here] revealed that higher BMI was associated with reduced anti-TNF treatment response and lower drug trough levels in children with Crohn’s disease treated with adalimumab (ADA) but not infliximab (IFX) initiators.

This suggested that monitoring of ADA trough levels in children with overweight and obesity might be necessary with adjustment of dosing within 6-12 weeks, said the US research team of paediatric gastroenterologists.

They conducted a secondary analysis from the COMBINE trial – the largest randomised controlled trial of paediatric IBD patients across 35 centres.

Of the 224 participants (65% male, mean age 14), 162 were treated with IFX initiators and 62 ADA initiators. Most participants (81%) had a healthy baseline BMI, while almost one in five (19%) had a high baseline BMI.

Among IFX-treated participants, there were no differences observed in treatment failure based on BMI with 26% of those with a healthy BMI experiencing treatment failure compared to 27% of those with a high BMI.

In contrast, ADA-treated participants with a healthy BMI had significantly lower treatment failure versus those with a high BMI (23% versus 70%).

Additionally, ADA-treated patients with a high BMI had lower adalimumab levels compared to those with a healthy BMI (median 5.8 µg/mL versus 12.8 µg/mL). Infliximab trough levels did not differ between the groups (8.6 µg/mL versus 9.3 µg/mL for healthy and high BMI, respectively).

However, the sample sizes for these analyses were small, consisting of 42 patients in the ADA-treated group and 109 patients in the infliximab group.

The researchers speculated that the lower response to standard ADA dosing among patients with overweight or obesity, and the frequent need to dose escalate, were due to fixed rather than weight-based dosing used for ADA.

In contrast, IFX dosing was weight-based, they noted.

“This may explain this finding of similar response rates and drug levels between IFX-treated patients with normal and high BMI,” they said.

They also said that pharmacokinetic studies had demonstrated that patients with obesity have increased drug clearance of anti-TNF with shortened half-life and lower trough drug concentrations compared to patients with a healthy weight, which might explain the differences in drug durability.

“Based on the findings of this study, proactive drug monitoring may be even more critical in paediatric patients with elevated BMI,” the authors said.

“When the dosing, and thus trough levels, can be optimised early, the study team speculates that patients may achieve remission sooner and hopefully maintain that remission longer.

“Prolonged remission decreases the many complications that can occur with Crohn’s disease such as use of steroids, growth failure, hospitalisations and surgery.”

Some authors received funding from pharmaceutical companies.

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