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

IF 6.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Anish J. Kuriakose Kuzhiyanjal, Jimmy K. Limdi
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引用次数: 0

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….

Anish J. Kuriakose Kuzhiyanjal: writing – original draft. Jimmy K. Limdi: writing – original draft, writing – review and editing.

The authors have nothing to report.

This article is linked to Desai et al papers. To view these articles, visit https://doi.org/10.1111/apt.18513 and https://doi.org/10.1111/apt.70125.

社论:肥胖和溃疡性结肠炎高级治疗的结果——脂肪的问题
肥胖症在世界范围内日益流行,对全球健康构成重大威胁。炎症性肠病(IBD)患者的身体质量指数(BMI)也呈上升趋势,15%-40%的成年患者报告为肥胖,20%-40%属于超重类别。肥胖通过脂肪因子和各种促炎细胞因子导致炎症状态,这引发了人们对肥胖在IBD发病机制、其自然史以及对医疗和外科治疗的影响中的潜在作用的好奇。最近的一项研究表明,与BMI正常的患者相比,肥胖的IBD患者有更高的活动性疾病和疾病相关复发的风险,溃疡性结肠炎(UC)的影响比克罗恩病(CD)的影响更大。此外,肥胖与药物清除加速、中心分布容积增加和不利的药代动力学有关[2,4]。一项综合荟萃分析表明,肥胖与UC(但与CD无关)中抗tnf衰竭的几率较高相关,但实际上没有其他生物疗法对IBD结局的疗效数据[10]。Desai等人利用TriNetX数据库报道了一项回顾性队列研究,研究肥胖对UC先进疗法疗效的影响,评估了肥胖IBD患者(BMI≥30 kg/m2)到非超重和非肥胖个体(BMI 18.5-24.9 kg/m2) bbb2年内皮质类固醇使用、先进疗法改变或结肠切除术的综合结果。他们发现肥胖IBD患者接受抗肿瘤坏死因子、维多单抗、ustekinumab和Janus激酶抑制剂(jak - 1)的复合结局风险增加。在维多单抗和抗tnf治疗的患者中,增加的风险扩展到超重队列(BMI 25-29.9 kg/m2),但不包括ustekinumab和jak - 1。尽管回顾性设计存在固有的局限性(没有索赔数据、住院或外部供应商的数据来自所使用的数据库的性质,ustekinumab和jak - 1的样本量较小),但本研究通过其清醒的观察结果增加了可信度,即UC患者的肥胖和高BMI与所研究的不良结果始终呈负相关。它也提出了一些重要的问题。使用BMI作为肥胖的衡量标准限制了区分内脏脂肪组织(VAT)和皮下脂肪的能力,它们具有不同的代谢和免疫特征[7]。前瞻性研究应探索VAT的体积分析,以与IBD结果相关联,并更好地调整混杂因素,如吸烟、类固醇使用和疾病活动。BMI测量时间的广泛变化以及吸烟、类固醇使用和疾病活动的混淆,模糊了我们对其对IBD自然史影响的理解。在IBD实践中实施常规腰围测量可以提高我们评估的质量,并为横断面和纵向研究提供数据。最后,肥胖在现代世界的普遍存在,为减肥(健康的生活方式、减肥内窥镜/手术以及胰高血糖素样肽-1 (GLP-1)激动剂)对IBD预后的影响提供了令人信服的论据[8,9]。我们祝贺德赛和他的同事为这一领域急需的进一步工作提供了动力。也许,当谈到脂肪的问题时,少即是多....
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.60
自引率
7.90%
发文量
527
审稿时长
3-6 weeks
期刊介绍: Alimentary Pharmacology & Therapeutics is a global pharmacology journal focused on the impact of drugs on the human gastrointestinal and hepato-biliary systems. It covers a diverse range of topics, often with immediate clinical relevance to its readership.
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