Patients with IBD and high abdominal fat may need more infliximab

Some Crohn's disease or ulcerative colitis patients do not respond to infliximab or its effect diminish for them. This could be related to visceral fat mass.

When is infliximab used for IBD?

Why is weight-adapted infliximab therapy inadequate?

In order to achieve a long-term remission, a certain trough level of infliximab is required. It can vary depending on individual patient characteristics and the respective course of the disease. However, it is still unclear what the optimal target dose is for each individual and how it can be measured. In the past, body weight was associated with increased infliximab clearance, which is why the antibody is administered in a weight-adapted manner.

However, the research team led by gastroenterologist Andres Yarur showed in a new study (DOI: 10.14309/ajg.0000000000002330) that this may not be sufficient. This is because the BMI (body mass index) says nothing about the specific body composition and is therefore only an inaccurate measure of obesity. However, visceral fat mass in particular could be responsible for the inadequate response of some patients to infliximab treatment.

To test this, the researchers included 142 patients with IBD in a prospective cross-sectional study. All received maintenance treatment with infliximab at the standard dose of 5 mg/kg every 8 weeks for at least 22 weeks. Body composition was analysed using a whole-body scan. In addition, disease activity, infliximab trough levels and various biomarkers were determined. The primary endpoint was steroid-free remission; the secondary endpoint was endoscopic remission within 8 weeks after the infliximab level was measured.

Depending on the visceral fat mass, different threshold values for infliximab were necessary to achieve steroid-free or endoscopic remission:

However, these differences were not seen in the examination of total body mass, which suggests that abdominal fat alone actually causes a higher infliximab clearance.

Why does abdominal fat play such an important role in the response to therapy?

The observation is consistent with previous clinical and experimental data suggesting that visceral adipose tissue is the key metabolically active component in obesity. Through the release of cytokines and adipokines, it could also play an important role in the pathogenesis of IBD.

However, the body fat percentage is probably only one of many variables for the relationship between the pharmacokinetics of infliximab and its clinical efficacy. The authors therefore do not believe that a universal trough level for infliximab can be determined. Rather, individual patient and disease factors must be taken into account when determining target values and, if necessary, dose changes. Therapeutic drug monitoring (TDM) could help to optimise the therapy.

Considerations for individualised therapy

A high proportion of visceral fat could explain why some patients do not respond adequately to treatment with infliximab. For them, a higher concentration of the active ingredient may lead to success. In the authors' opinion, this should be considered before discontinuing treatment prematurely.