September 5, 2023
Does intra-abdominal fat impact outcomes with biologics in patients with IBD?
Higher intra-abdominal visceral adipose tissue mass may predict an attenuated response to biologic therapy in IBD, but more data are needed to confirm, better characterize and explain this relationship.
Yarur AJ, Bruss A, Moosreiner A, et al. Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated with Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study. Gastroenterol. Epub ahead of print July 25, 2023; https://j.gastro.2023
Prior research has suggested obesity and high intra-abdominal visceral adipose tissue (IA-VAT) mass are associated with poorer outcomes in IBD. To investigate the relationship between IA-VAT and outcomes specifically with biologics, investigators prospectively studied 79 patients with active Crohn’s disease (CD) and 62 with active ulcerative colitis (UC). Fifty-two patients were initiating treatment with infliximab, 46 were starting vedolizumab therapy and 43 were starting ustekinumab treatment.
Baseline IA-VAT as a percent of total body mass (IA-VAT%) was calculated using dual energy X-ray absorptiometry scan, a technique commonly used to assess bone density.
The researchers found that 14–16 weeks and 30–32 weeks after treatment initiation, 34% and 40%, respectively, of all IBD patients achieved corticosteroid-free deep remission (SFDR), defined as a Harvey Bradshaw Index <5 for CD and a partial Mayo score <2 for UC, along with a normal C-reactive protein and fecal calprotectin. Rates of SFDR at 14–16 weeks were 48.6% and 57.1% for the two lowest IA-VAT% quartiles, compared to 25.7% and 5.6% for the two highest quartiles of IA-VAT% (p<0.001).
Endoscopic remission, defined as a Mayo Score ≤1 in UC patients or a Simple Endoscopic Score for CD ≤2 at 30–46 weeks, was also lower with higher IA-VAT%. Rates of this outcome ranged from 60.7% to 63% in the two lowest quartiles of IA-VAT%, respectively, to 42.9% and 24% in the two highest quartiles of IA-VAT% (p=0.02).
There were no significant differences in drug pharmacokinetics in the high vs. low IA-VAT% groups, but non-responders with high IA-VAT% had significantly higher baseline levels of serum interleukin-6 and tumor necrosis factor than responders as well as those with low IA-VAT%.
Multivariate analysis found several independent predictors of SFDR at 14–16 weeks, including higher IA- VAT% (Odds Ratio [OR] per 1% increase in IA-VAT%: 0.4; 95% Confidence Interval [CI], 0.16–0.98), prior exposure to biologics (OR: 3.5; 95% CI, 1.43–8.53), baseline C-reactive protein (OR: 0.72; 95% CI, 1.02–1.09) and drug levels higher than the median of patients receiving one of the three types of biologics (OR, 2.97; 95% CI, 1.20–7.32).
Study Design: Prospective observational cohort
Funding: The Digestive Disease Center at the Medical College of Wisconsin and National Institutes of Health Clinical and Translation Science.
Allocation: Not applicable
Level of Evidence: 1b