Exploring the role of monitoring anti-TNFα drug and antibody levels in the management of inflammatory bowel disease

Lim, Allen; Panaccione, Remo; Seow, Cynthia H.

doi:10.1177/1756283x10382816

Cited by 6 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 In clinical studies, different types of anti-TNF-α agents have shown efficacy in treatments of both UC and CD. 45 This evidence suggests that SCFA-mediated suppression of inflammatory signaling and cytokine expression induced by TNF-α could contribute to the prevention of intestinal inflammation. We found that SCFAs did not influence the expression of IL-10, an anti-inflammatory cytokine mainly produced by regulatory T cells, in cultures of both normal and inflamed colonic segments.…”

Section: ■ Discussionmentioning

confidence: 99%

Short-Chain Fatty Acids Suppress Inflammatory Reactions in Caco-2 Cells and Mouse Colons

Hung

Suzuki

2017

J. Agric. Food Chem.

View full text Add to dashboard Cite

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, play an important role in the maintenance of intestinal homeostasis. In the present study, anti-inflammatory effects of SCFAs were examined in human intestinal Caco-2 cells and mouse colonic cultures. Stimulation of Caco-2 cells with tumor necrosis factor (TNF)-α induced interleukin (IL)-8 (TNF-α, 17.1 ± 7.2 vs Control, 1.00 ± 0.26, P < 0.01) and IL-6 expression (TNF-α, 21.7 ± 10.0 vs Control, 1.00 ± 0.28, P < 0.01) through the activation of nuclear factor κB p65, spleen tyrosine kinase, and mitogen-activated protein kinase pathways. Pretreatment of cells with acetate (5 mM, IL-8 1.23 ± 0.40, IL-6 2.19 ± 0.92, P < 0.01 ), propionate (2.5 mM, IL-8 2.45 ± 2.10, IL-6 2.19 ± 0.92, P < 0.01), or butyrate (0.625 mM, IL-8 1.44 ± 0.70, IL-6 2.31 ± 0.32, P < 0.01) suppressed inflammatory responses induced by TNF-α. Pharmacological inhibition of monocarboxylate transporter (MCT)-1 attenuated the suppression of inflammatory signals by SCFAs. High expression levels of CXC motif chemokine ligand 2 (CXCL2, an IL-8 homologue, DSS, 31.7 ± 9.8 vs Control, 1.00 ± 0.70, P < 0.01) and IL-6 (DSS, 17.5 ± 7.2 vs Control, 1.00 ± 0.68, P < 0.01) were observed in BALB/c mouse colonic cultures exposed to dextran sodium sulfate, whereas treatments with mixtures of SCFAs decreased these elevated expression levels (CXCL2 4.14 ± 2.88, IL-6 0.58 ± 0.28, P < 0.01). Our results suggest that SCFAs transported by MCT-1 suppress TNF-α-induced inflammatory signaling in intestinal cells.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

Short-Chain Fatty Acids Suppress Inflammatory Reactions in Caco-2 Cells and Mouse Colons

Hung

Suzuki

2017

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…Intensification is also not effective in patients whose treatment failure is due to different mechanisms. Therefore, in this clinical situation, the first step is to verify the presence of active inflammation, rule out disease complications or other causes of the symptoms (stenosis, abscesses, infection, amyloidosis, bile acid malabsorption and irritable bowel) [20,47,78]. In the studies performed to date, up to 40% of patients with symptoms suggestive of exacerbation do not present active inflammation.…”

Section: Use In Clinical Practicementioning

confidence: 99%

Monitoring Anti-Tnf Drug Treatment in Inflammatory Bowel Disease. Is it Useful in Clinical Practice?

Martín-Arranz¹

2016

GHOA

View full text Add to dashboard Cite

Despite the efficacy demonstrated by anti-TNF drugs in treating inflammatory bowel disease, there is a significant percentage of patients for whom the drugs fail or the response to the drugs is lost. The limitations in managing these patients and the increase in costs necessitate an individualised strategy to optimise their clinical management. Recent studies have noted the relationship between the clinical outcome and therapeutic adjustments based on monitoring anti-TNF levels and the presence of antibodies, taking into account other factors such as the type of disease and its severity. This study reviews the available information and proposes a clinical management algorithm to achieve a more efficient result.

show abstract

“…Estimates of the level of primary non-response vary, depending on the definition of response. The number of patients with acute refractory UC failing to show a response (!3 point and !30% decrease in Mayo score, and !1 point decrease in rectal-bleeding subscore or absolute rectal-bleeding subscore of 1) to infliximab after 8 weeks of treatment in two phase III studies was reported to be 30-40% 15 . A systematic review and clinician survey conducted in the UK and France reported that 19-48% of patients fail to respond to treatment with infliximab 13 .…”

Section: Introductionmentioning

confidence: 99%

Living with ulcerative colitis in Germany: a retrospective analysis of dose escalation, concomitant treatment use and healthcare costs

Dignaß

Waller

Cappelleri

et al. 2020

Journal of Medical Economics

View full text Add to dashboard Cite

Aims: To investigate treatment of moderate-to-severe ulcerative colitis (UC) using real-world German health insurance claims data. Materials and methods: A retrospective, longitudinal cohort study was conducted from a German statutory health insurance database for adult patients with UC indexed on biologic therapy initiation (2013-2015). Anonymized data were evaluated for 12 months prior to (baseline) through 24 months after (follow-up) indexing. Biologic dose escalations, steroid and immunosuppressant use, healthcare resource utilization (HCRU) and direct healthcare costs were evaluated, with significant differences assessed across and between index biologics. Descriptive statistics, chi-square or Fisher's exact tests, and analysis of variance were performed. Results: The analysis included 304 patients (adalimumab, n ¼ 125; golimumab, n ¼ 47; infliximab, n ¼ 114; vedolizumab, n ¼ 18). Demographic and clinical characteristics were similar across biologics. Dose escalations occurred in 58% of patients (73% of patients receiving adalimumab), with 41% receiving subsequent de-escalation. Steroids were used during follow-up by 74% of patients; 25% received steroids >14 weeks after indexing. Overall, 41% of patients received an immunosuppressant during follow-up. Steroid and immunosuppressant use were similar across biologics. Total direct healthcare costs were higher during follow-up than baseline and differed significantly across treatments (p < .05), with highest costs for golimumab. Biologic costs contributed to a major portion of follow-up costs. HCRU and costs for most resources were higher in the first 12-month follow-up period than baseline. All resource use except gastroenterology visits returned to, or below, baseline levels 13-24 months post-index date. Limitations: There was potential for inappropriate inclusion/exclusion due to miscoding. Patients may have received biologics >12 months prior to the index date. Biologic originators and biosimilars could not be differentiated. Conclusions: These data suggest that control with current biologics is suboptimal. Further treatment options that provide sustained steroid-free remission for this patient population without the need for dose escalations or concomitant therapies may be warranted.

show abstract

Exploring the role of monitoring anti-TNFα drug and antibody levels in the management of inflammatory bowel disease

Cited by 6 publications

References 28 publications

Short-Chain Fatty Acids Suppress Inflammatory Reactions in Caco-2 Cells and Mouse Colons

Short-Chain Fatty Acids Suppress Inflammatory Reactions in Caco-2 Cells and Mouse Colons

Monitoring Anti-Tnf Drug Treatment in Inflammatory Bowel Disease. Is it Useful in Clinical Practice?

Living with ulcerative colitis in Germany: a retrospective analysis of dose escalation, concomitant treatment use and healthcare costs

Contact Info

Product

Resources

About