No Adverse Impact of Obesity in Biologic-Treated IBD

Liam Davenport

July 04, 2022

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter US study published online in American Journal of Gastroenterology.

"Our findings were a bit surprising since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics," Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, in La Jolla, told Medscape Medical News.

"However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect," he said.

Based on the findings, Singh believes that biologics are "completely safe and effective to use in obese patients."

He clarified, however, that "examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission."

"Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity," he said.

Research Findings

Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an "increasingly important consideration" in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between January 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization vs normal BMI (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.

Reassuring Results for the Standard of Care

Discussing their findings, the authors note that "the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity."

"A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD."

Singh said that it would be "very interesting" to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, Illinois, said, "At the present time, there are no new clinical implications based on this study."

He told Medscape Medical News that it "does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients."

"With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients," Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn's and Colitis Foundation Career Development Award to Singh. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Hanauer reports no relevant financial relationships.

Am J Gastroenterol. Published online June 7, 2022. Abstract

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