Evaluation of anti-TNF therapeutic response in patients with inflammatory bowel disease: Current and novel biomarkers

Cui, Guanglin; Fan, Qingfeng; Li, Zhenfeng; Goll, Rasmus; Florholmen, Jon

doi:10.1016/j.ebiom.2021.103329

Cited by 52 publications

(25 citation statements)

References 88 publications

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“…Next, the detection of gene biomarkers with the potential capability of differentiating non-responders from responders to anti-TNF therapy is clearly an unmet need in the management of CD at present. Several clinical biomarkers, which serve as reproducible as well as quantitative tools to assess therapeutic efficacy during anti-TNF therapy, have been previously investigated in IBD patients, including C-reactive proteins, faecal calprotectins, and anti-TNF drug levels [ 9 ]. However, at present, no clinical predictors exist that predict the anti-TNF therapy response at baseline prior to its application, even though preemptive prediction can serve to be more meaningful in the individualised management of CD.…”

Section: Discussionmentioning

confidence: 99%

“…To date, few methods based solely on clinical parameters and disease activity scores have been suggested to study the response to anti-TNF therapy in CD. Furthermore, they do not yield the required efficacy, even for a baseline primary response [ 9 ]. Therefore, a clear understanding of their resistance mechanisms and the pre-treatment assessment of anti-TNF therapy responsiveness in CD are critical for patients who may be susceptible to severe adverse effects of the drug that they may not benefit from, their families, and healthcare systems that endure the additional economic liability due to poor disease outcome.…”

Section: Introductionmentioning

confidence: 99%

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Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn’s Disease

Kwak

Myung

Jeon

et al. 2022

JFB

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Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn’s disease (CD) in clinical practice. However, differential individual response necessitates a therapeutic response assessment of anti-TNF agents in CD patients for optimizing therapeutic strategy. We aimed to predict anti-TNF therapy response in CD patients using transcriptome analyses. Transcriptome analyses were performed using data from the Gene Expression Omnibus, GeneCards, and Human Protein Atlas databases. The significantly mitigated biological functions associated with anti-TNF therapy resistance in CD patients encompassed immune pathways, including Interleukin-17 (IL-17) signaling, cytokine-cytokine receptor interaction, and rheumatoid arthritis. The scores of immune cell markers, including neutrophils, monocytes, and macrophages/monocytes were also significantly decreased in non-responders compared with that measured in anti-TNF therapy responders. The KAT2B gene, associated with IL-17 cytokine mediated neutrophil mobilization and activation, was significantly under-expressed in both tissue and peripheral blood mononuclear cells (PBMCs) in anti-TNF therapy-resistant CD patients. The reduced expression of several pro-inflammatory cytokines due to down-regulated IL-17 signaling, is suggestive of the primary non-response to anti-TNF agents in CD patients. Furthermore, the PBMC KAT2B gene signature may be a promising pre-treatment prognostic biomarker for anti-TNF drug response in CD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn’s Disease

Kwak

Myung

Jeon

et al. 2022

JFB

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“…Fecal calprotectin is commonly used for monitoring the response to treatment and healing of the intestinal mucosa [38,39]. In the only previous study examining the effect of biologic therapy for IBD on salivary parameters, Majster et al [40] compared calprotectin levels in saliva before and after therapy.…”

Section: Discussionmentioning

confidence: 99%

Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease

Nijakowski

Rutkowski

Eder

et al. 2021

Life

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We previously observed that inflammatory bowel disease (IBD) may compromise oral host defense, as assessed by decreased salivary levels of immunoglobulin A (IgA) and myeloperoxidase (MPO). Biologic therapy with inhibitors of cytokines or adhesion molecules is increasingly used for patients with IBD. Little is known, however, about how this treatment modality affects the release and properties of saliva. Here, we aimed to determine how biologic therapy in patients who had not responded to previous standard treatment with conventional drugs affected the salivary concentration of IgA and MPO. To this end, unstimulated whole mixed saliva was collected before treatment or after 10–12 weeks of therapy from 27 patients with Crohn’s disease (CD) and 24 patients with ulcerative colitis (UC). After the induction phase of therapy with biologics, salivary levels of IgA and MPO increased significantly in UC, but not in CD patients. These increases were approximately 8-fold and 6-fold, for IgA and MPO, respectively. Moreover, these effects occurred in UC patients who responded successfully to therapy, but not in those who failed to improve. Furthermore, the relative increases in salivary IgA and MPO correlated with the relative decrease in UC severity, as assessed by the Mayo scale. These data indicate that the successful therapy with biologics in UC patients results also in improved oral host defense. However, it remains to be determined why such an effect does not occur during therapy for CD.

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“…In recent years, many data on biomarkers that are expected to be used in the daily clinical practice of IBD have accumulated [157,158]. MicroRNAs (miRNAs) are a singlestranded RNA of about 21 to 25 bases that negatively regulates gene expression [159].…”

Section: Novel Biomarkersmentioning

confidence: 99%

Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

Wagatsuma

Yokoyama

Nakase

2021

Life

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The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Endoscopy is the gold standard to assess the condition of IBD. The problem with this procedure is that the burden and cost on the patient are high. Therefore, the identification of a reliable biomarker to replace endoscopy is desired. Biomarkers are used in various situations such as diagnosis of IBD, evaluation of disease activity, prediction of therapeutic effect, and prediction of relapse. C-reactive protein and fecal calprotectin have a lot of evidence as objective biomarkers of disease activity in IBD. The usefulness of the fecal immunochemical test, serum leucine-rich glycoprotein, and urinary prostaglandin E major metabolite have also been reported. Herein, we comprehensively review the usefulness and limitations of biomarkers that can be used in daily clinical practice regarding IBD. To date, no biomarker is sufficiently accurate to replace endoscopy; however, it is important to understand the characteristics of each biomarker and use the appropriate biomarker at the right time in daily clinical practice.

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Evaluation of anti-TNF therapeutic response in patients with inflammatory bowel disease: Current and novel biomarkers

Cited by 52 publications

References 88 publications

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn’s Disease

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn’s Disease

Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease

Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

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