Editorial: Obesity and Outcomes on Advanced Therapy in Ulcerative Colitis—The Fat of the Matter

Abstract

The increasing prevalence of obesity worldwide poses a major threat to global health [1]. The body mass index (BMI) of individuals with inflammatory bowel disease (IBD) has also undergone an upward shift, with 15%–40% of adult patients reported to be obese and 20%–40% in the overweight category [2]. Obesity contributes to an inflammatory state through adipokines and various pro-inflammatory cytokines, sparking curiosity about the potential role of obesity in IBD pathogenesis, its natural history, and impact on medical and surgical management [2]. A recent study demonstrated that obese patients with IBD had a higher risk of having active disease and disease-related relapse compared to patients with a normal BMI, an effect stronger in ulcerative colitis (UC) than Crohn's disease(CD) [3]. Additionally, obesity is associated with accelerated drug clearance, increased central volume of distribution, and unfavourable pharmacokinetics [2, 4]. A pooled meta-analysis demonstrated that obesity was associated with higher odds of anti-TNF failure in UC (but not CD) but there are virtually no data on the efficacy of other biologic therapies on IBD outcomes [5].

Adding to our understanding, Desai et al. report a retrospective cohort study, utilising the TriNetX database, of the impact of obesity on the efficacy of advanced therapies in UC, assessing a composite outcome of corticosteroid use, change in advanced therapy, or colectomy within 2 years among IBD patients with obesity (BMI ≥ 30 kg/m²) to non-overweight and non-obese individuals (BMI 18.5–24.9 kg/m²) [6]. They identified an increased risk of the composite outcome in obese IBD patients receiving anti-TNF agents, vedolizumab, ustekinumab, and Janus Kinase inhibitors (JAK-i). The increased risk extended to the overweight cohort (BMI 25–29.9 kg/m²) in vedolizumab and anti-TNF treated patients, but not ustekinumab and JAK-i.

Inherent limitations posed by the retrospective design notwithstanding (no claims data, hospitalisation or external provider data from the nature of the database used, smaller sample sizes for ustekinumab and JAK-I), this study adds credence through its sobering observation that obesity and high BMI in UC are consistently and negatively associated with the undesirable outcomes studied.

It also raises important questions. The use of BMI as a measure of obesity limits the ability to differentiate visceral adipose tissue (VAT) from subcutaneous fat, with distinct metabolic and immunological profiles [7]. Prospective studies should explore volumetric analysis of VAT to correlate with IBD outcomes and better adjustment of confounders such as smoking, steroid use and disease activity. The potential for wide variation in the timing of BMI measurements and confounding by smoking, steroid use, and disease activity blur our understanding of its impact on IBD natural history. Implementing routine measurement of waist circumference in IBD practice should improve the quality of our assessments and provide data for cross-sectional and longitudinal studies. Finally, the pervasiveness of obesity in the modern world makes a compelling argument for data on weight loss (healthy lifestyle, bariatric endoscopy/surgery and indeed glucagon-like peptide-1 (GLP-1) agonists) on IBD outcomes [8, 9]. Desai and colleagues are to be congratulated for providing impetus to much-needed further work in this area. Perhaps, when it comes to the matter of fat, less is more….