Mutations in the <i>NOD2</i> gene are associated with a specific phenotype and lower anti‐tumor necrosis factor trough levels in Crohn's disease

Schäffler, Holger; Geiss, D; Gittel, N; Rohde, Sarah L.; Huth, A; Glass, Änne; Brandhorst, Gunnar; Jaster, Robert; Lamprecht, Georg

doi:10.1111/1751-2980.12677

Cited by 16 publications

(8 citation statements)

References 33 publications

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“…Several studies have demonstrated an increased carrier rate of these three mutations of the NOD2 gene in patients with CD compared with healthy controls[11,12]. Recently, associations of mutations in the NOD2 gene and specific phenotypes, as well as lower anti-TNF-α trough levels, were shown in patients with CD[13]. Nothing is known about potential associations between NOD2 mutations and the efficacy of ustekinumab in CD.…”

Section: Introductionmentioning

confidence: 99%

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

Hoffmann¹,

Krisam²,

Wehling³

et al. 2019

WJG

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BACKGROUND Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease (CD) in 2016, and there is an urgent need for data on its everyday use. AIM To obtain data on the daily use of ustekinumab. METHODS This is a retrospective monocentric study. Patients with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient files. The primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24 ± 6 wk of ustekinumab therapy. Secondary study endpoints were: achievement of mucosal healing, sonographic and magnetic resonance imaging response, biochemical response, the need for intestinal surgery within 24 ± 6 wk after treatment initiation, the occurrence of adverse events, treatment discontinuation due to nonresponse or adverse events, improvement of extraintestinal manifestations, clinical response at 48 ± 6 wk of therapy, and association of response with nucleotid oligodimerisation domain 2 mutations. RESULTS Fifty-seven patients with CD (5.3% anti-tumour necrosis factor α naïve, 63.2% having undergone at least one intestinal surgery) were included in the study. Twenty patients (35.1%) achieved steroid-free clinical remission, 6 (10.5%) steroid-free clinical response and 31 (54.4%) were non-responders. Treatment discontinuation due to adverse events occurred in two patients (3.5%). Male sex, the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy. CONCLUSION In a “real-world” treatment-refractory cohort of patients with CD, ustekinumab appeared efficacious and safe.

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Section: Introductionmentioning

confidence: 99%

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

Hoffmann¹,

Krisam²,

Wehling³

et al. 2019

WJG

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“…Fourth, because NOD2 polymorphisms are associated with complex courses of CD and the need for surgery, 43,44 the influence of NOD2 mutation on the prevalence of malnutrition was studied. Interestingly, although there was a trend among CD patients with a mutation in the NOD2 gene toward a higher probability of active disease (CDAI ≥150) compared to those without NOD2 gene mutation, this was not associated with a higher incidence of malnutrition in patients with NOD2 gene mutation.…”

Section: Discussionmentioning

confidence: 99%

Body impedance analysis to estimate malnutrition in inflammatory bowel disease patients – A cross‐sectional study

Reiner

Koch

Woitalla

et al. 2022

J of Digest Diseases

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Objective: Malnutrition is a common clinical problem in patients with inflammatory bowel diseases (IBD). However, a gold standard for the detection of malnutrition in IBD patients is lacking.Methods: A cross-sectional study to assess malnutrition in patients with IBD and healthy controls (HCs). Clinical characteristics (Montreal classification, disease activity, previous surgery) and mutations in the NOD2 gene in patients with Crohn's disease (CD) were obtained. We performed a nutritional assessment with screening for nutritional risk and diagnosis for malnutrition (Malnutrition Universal Screening Tool [MUST]) score, NRS-2002, European Society for Clinical Nutrition and Metabolism (ESPEN), and Global Leadership Initiative on Malnutrition (GLIM) criteria and performed body impedance analysis (BIA). Results: 101 IBD patients (57 CD and 44 ulcerative colitis (UC) and 50 HC were included in a single northern German tertiary center. GLIM criteria detected malnutrition significantly more often compared to the ESPEN criteria. Active disease, a longstanding disease course, and previous surgery were associated with reduced muscle mass. IBD patients had a higher fat mass index compared to HC. Mutations in the NOD2 gene had no effect on nutritional status. Conclusions:The GLIM criteria detect malnutrition at a higher rate compared to ESPEN. Specific disease factors might put IBD patients at a higher risk for the development of malnutrition, so these patients might benefit from a frequently performed screening, which might result in a favorable disease course. | INTRODUCTIONInflammatory bowel disease (IBD) is a group of disorders of the alimentary tract that mainly consist of two entities, Crohn's disease (CD) and ulcerative colitis (UC). 1 While the pathogenesis of IBD is still not completely understood, it is well known that inappropriate activation of the mucosal immune system is caused by intestinal microbiota in patients with genetic risk profile 1-4 such as mutation in the NOD2 gene. 5-7 A broader evaluation of potential individual patient needs involves estimation of malnutrition, which is a common phenomenon in IBD and may present in 20%-70% of CD or UC patients. [8][9][10][11] However, it is more common in CD. 12 In IBD, disturbed digestion may interfere with absorption and trigger malnutrition. In turn, malnutrition may also negatively influence the disease

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“…The NOD2 gene is associated with CD susceptibility and with a more aggressive course of disease [54,55]; it encodes for a protein that plays a role in eliciting the immune response and is implicated in the inflammatory pathway of TNF. Some studies have found an association between NOD2 variants and worse response to anti-TNF therapy [41][42][43]. Polymorphisms in the ATG16L1 gene have been associated better response rates [44] and longer benefit [46] in CD patients treated with TNF antagonists.…”

Section: Genetic Markersmentioning

confidence: 99%

Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

Privitera

Pugliese

Rapaccini

et al. 2021

JCM

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Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

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Mutations in the NOD2 gene are associated with a specific phenotype and lower anti‐tumor necrosis factor trough levels in Crohn's disease

Cited by 16 publications

References 33 publications

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

Body impedance analysis to estimate malnutrition in inflammatory bowel disease patients – A cross‐sectional study

Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

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