More Visceral Fat Associated With Less Remission in Inflammatory Bowel Disease

An increased percentage in intra-abdominal visceral adipose tissue (IA-VAT%) was independently associated with worse outcomes in patients with inflammatory bowel disease (IBD) initiating biologic therapy, according to study results published in Gastroenterology.

The prospective, observational CONSTELLATION study enrolled patients aged at least 18 years with a confirmed diagnosis of Crohn disease (CD) or ulcerative colitis (UC) or healthy, age-, and sex-matched control individuals between May 2017 and September 2021. The patients were screened at the time of treatment initiation with standard dosing of infliximab, vedolizumab, or ustekinumab.

The primary outcome was corticosteroid-free deep remission (SFDR) at week 14/16, which was a composite of Harvey-Bradshaw index (HBI) less than 5 in CD or a Partial Mayo score of less than 2 in UC, combined with a serum C-reactive protein of 0.5 mg/dL or less and a fecal calprotectin of 150 μg/mg or less of stool, when off corticosteroids.

The cohort included 192 patients (141 with IBD and 51 matched control individuals); 79 participants had CD and 62 had UC. Of the IBD group, 52, 46, and 43 patients initiated infliximab, vedolizumab, and ustekinumab, respectively. The IBD and the healthy control groups had similar body composition parameters.

A total of 48 (34.0%) and 51 (40.0%) participants had SFDR at weeks 14/16 and 30/32, respectively. The rates of SFDR postinduction at weeks 14/16, during maintenance at weeks 30/32, and endoscopic remission were significantly decreased for patients who were in the highest 2 IA-VAT% quartiles.

An increased IA-VAT% (odds ratio [OR] per % increase, 0.4; 95% CI, 0.16-0.98), prior use of biologics (OR, 3.499; 95% CI, 1.43-8.53), and drug levels in the highest 2 quartiles for each biologic (OR, 2.97; 95% CI, 1.20-7.32]) were independently associated with the failure for SFDR at weeks 14/16.

After adjustment for factors significantly associated with SFDR at weeks 30/32 in the univariate analysis, weeks 30/32 drug levels in the 2 lowest quartiles for each biologic and elevated IA-VAT% were independently associated with the inability to achieve SFDR at weeks 30/32 (OR, 0.26; 95% CI, 0.10-0.68 and OR, 0.25; 95% CI, 0.09-0.64, respectively).

Patients in the high baseline IA-VAT% quartiles had comparable infliximab drug levels at week 14 vs those with low IA-VAT%, and patients with a high IA-VAT% did not have an increased vedolizumab drug level at week 14 vs those with low IA-VAT%. Participants in the high IA-VAT% quartiles had a nonsignificantly increased ustekinumab drug level at week 14 vs those in the low IA-VAT% quartiles.

IA-VAT% had a positive correlation with interleukin-6 and tumor necrosis factor-α (rho: 0.37 [P =.01] and rho: 0.53 [P <.001], respectively.

Limitations include the noninterventional nature of the study and absence of a standardized corticosteroid taper. Also, the definition of high and low IA-VAT% was based on the study population, and the different types of IA-VAT were not differentiated.

“A higher IA-VAT% burden is associated with lower response to therapy with infliximab, vedolizumab, or ustekinumab in both CD and UC,” study authors wrote. “While the exact mechanisms of these findings warrant further investigation, the overexpression of certain cytokines may play an important role.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.