IBD patients with higher intra-abdominal fat less likely to respond to biologic therapy
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Key takeaways:
- Higher levels of intra-abdominal visceral adipose tissue correlated with worse outcomes in patients with IBD.
- This association could result from differences in inflammatory cytokine expression.
Patients with inflammatory bowel disease and a higher percentage of intra-abdominal visceral adipose tissue were less likely to achieve corticosteroid-free remission when treated with biologics, according to data in Gastroenterology.
“Even though biologic medications have significantly improved outcomes for our patients with Crohn’s disease or ulcerative colitis, some people do not respond well to these therapies,” Andres J. Yarur, MD, study author and associate professor of gastroenterology and hepatology at Cedars-Sinai in Los Angeles, said in a related press release. “In our study, we found that the patients with higher amounts of internal abdominal fat were less likely to improve and experience remission from their disease.”
Yarur and colleagues conducted a prospective, observational cohort study to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to three biologics. Researchers enrolled 141 adult patients with IBD who received standard dosing of infliximab (n = 52), vedolizumab (n = 46) or ustekinumab (n = 43) and compared them with 51 healthy controls.
Participants were evaluated at baseline, after biologic induction (week 14 for infliximab and vedolizumab and week 16 for ustekinumab) and at week 30 of maintenance therapy for infliximab and vedolizumab and week 32 for ustekinumab. Lean mass, total adipose tissue and IA-VAT was measured at baseline.
The primary outcome was corticosteroid-free deep remission (SFDR) at week 14 or 16; secondary outcomes included SFDR at week 30 or 32 and endoscopic remission at weeks 30 through 46.
According to study results, 34% of participants achieved SFDR at week 14 or 16 and 40% at week 30 or 32. In the infliximab group, 32.7% achieved SFDR at week 14 and 46.3% at week 30, while 39.1% and 41.4% achieved SFDR at those time points in the vedolizumab group. In the ustekinumab group, 30.2% achieved SFDR at week 16 and 28.5% at week 32.
Multivariable analysis showed higher IA-VAT (OR per percent increase = 0.4; 95% CI, 0.16-0.98), previous biologic exposure (OR = 3.499; 95% CI, 1.43-8.53) and drug levels in the highest two quartiles for each biologic (OR = 2.97; 95% CI, 1.2-7.32) were independently linked with failure to achieve SFDR at week 14 or 16.
Further, failure to achieve SFDR at week 30 or 32 was independently associated with drug levels in the two lowest quartiles for each biologic (OR = 0.26; 95% CI, 0.1-0.68) and high IA-VAT (OR = 0.25; 95% CI, 0.09-0.64).
Results also showed that high IA-VAT correlated with higher interleukin-6 and tumor necrosis factor among non-responders at baseline compared with responders and those with low IA-VAT. Researchers reported no differences in drug pharmacokinetics and microbiota diversity between the high and low IA-VAT groups.
“We found that higher visceral adiposity was associated with higher levels of pro-inflammatory cytokines, suggesting that fat tissue promotes inflammation, the opposite of what we want, and increases resistance to biologic drug therapy,” Gil Y. Melmed, MD, MS, study author and director of IBD clinical research at Cedars-Sinai, said in the release.
Yarur added: “We need to investigate drugs with different mechanisms of action, especially other small molecules, to see if our findings hold. As the prevalence of obesity and metabolic syndrome increases in our population, we need to find interventions that would improve the body composition of these IBD patients who are not currently helped by these biologic treatments.”
Reference:
- Belly fat hinders digestive disease medications. https://www.cedars-sinai.org/newsroom/digestive-disease-medications-hindered-by-body-fat/. Published July 25, 2023. Accessed Aug. 03, 2023.
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