TNF-Alpha Blockers in Inflammatory Bowel Diseases: Practical Recommendations and a User’s Guide: An Update

Vulliemoz, Marianne; Brand, Stephan; Juillerat, Pascal; Mottet, Christian; Ben‐Horin, Shomron; Michetti, Pierre

doi:10.1159/000506898

Cited by 59 publications

(50 citation statements)

References 87 publications

(105 reference statements)

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“… 24 , 30 Considering the lack of standardized strategies for ATI management, IFX therapies are sometimes merely IFX trough level guided. 1 , 10 – 14 Notably, IFX levels and related indices did not predict LOR in our study. Regarding the S ATI group comparisons, this surprising observation may, on the one side, be caused by limiting the analyzed data to the time window T 0–3 .…”

Section: Discussioncontrasting

confidence: 74%

See 1 more Smart Citation

Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Grasmeier

Langmann

et al. 2021

Therap Adv Gastroenterol

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Background: Antibodies to infliximab (ATI) in serum are associated with secondary loss of response (LOR) to infliximab (IFX) therapy in patients with inflammatory bowel disease (IBD). However, feasible ATI-related predictors of therapy success are lacking and knowledge about individual ATI dynamics is limited. Therefore, this study analyzed whether ATI dynamics are able to predict LOR to IFX therapy and compared their predictive power with known predictors of LOR to IFX. Methods: This was a retrospective study of patients with Crohn’s disease (CD) or ulcerative colitis (UC) on IFX maintenance therapy and proactive IFX and immunogenicity monitoring in an outpatient clinic in Germany. Slopes of ATI ( SATI) and IFX levels (dynamic parameters) and medians of ATI, IFX, C-reactive protein, and fecal calprotectin (static parameters) were calculated over a defined period of time after ATI emergence. Dynamic and static parameters were analyzed for associations with end points infliximab discontinuation due to secondary LOR and total IFX discontinuation. Results: In all, 500 visits from 38 IBD patients (28 CD, 10 UC) with a median IFX maintenance duration of 68.2 weeks were evaluated. Grouping by SATI (ATI-N = ATI nondetectable, ATI- ↓ = negative SATI, ATI- ↑ = positive SATI) yielded significant differences for outcomes LOR ( p = 0.004) and total IFX discontinuation ( p = 0.01). Patients in the ATI-↓ group survived significantly longer LOR-free compared with the ATI-↑ group ( p = 0.02). Cox regression confirmed SATI to be a significant risk factor for LOR ( p = 0.002). An SATI cut-off of approximately 2.0 AU mL−1 week−1 was determined to predict LOR with 83.3% sensitivity and 93.8% specificity. Conclusion: The ATI slope-based index SATI is a new feasible diagnostic predictor of LOR in IBD patients. SATI may facilitate quick therapeutic decisions after ATI emerge.

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Section: Discussioncontrasting

confidence: 74%

“…TNF antagonists are considered as disease-modifying drugs and constitute powerful tools to achieve clinical and endoscopic remission. 1 After initial approval, TNF antagonists were indicated as penultimate measure before surgery within the step-care approach. Nowadays, the use of TNF antagonists has shifted toward early intervention.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Grasmeier

Langmann

et al. 2021

Therap Adv Gastroenterol

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“…Several trials have demonstrated the efficacy of infliximab in induction and maintenance of remission of CD and UC in patients and subsequently further trials showed adalimumab has a similar therapeutic benefit in inducing and maintaining remission of disease leading to their use for UC and CD in clinical practice. Golimumab has since been shown to have efficacy in UC and certolizumab in CD; the latter is approved for CD in US but not in EU [65] , [66] .…”

Section: Role Of Tnf-alpha Inhibitors In Inflammatory Bowel Diseasementioning

confidence: 99%

Therapeutic use of specific tumour necrosis factor inhibitors in inflammatory diseases including COVID-19

Patel¹,

Wadhwa²

2021

Biomedicine & Pharmacotherapy

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Coronavirus disease 2019 (COVID-19) has caused significant devastation globally. Despite the development of several vaccines, with uncertainty around global uptake and vaccine efficacy, the need for effective therapeutic agents remains. Increased levels of cytokines including tumour necrosis factor are significant in the pathogenesis of COVID-19 and associated with poor outcomes including ventilator requirement and mortality. Repurposing tumour necrosis factor blocker therapy used in conditions such as rheumatoid arthritis and inflammatory bowel disease seems promising, with early feasibility data showing a reduction in circulation of pro-inflammatory cytokines and encouraging the evaluation of such interventions in preventing disease progression and clinical deterioration in patients with COVID-19. Here, we examine the biological activities of tumour necrosis factor inhibitors indicative of their potential in COVID-19 and briefly outline the randomised control trials assessing their benefit-risk profile in COVID-19 therapy.

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“…Interestingly, DSSregulated genes of Th17 cells in cluster 0 were highly enriched in TNF and NFB signaling pathways. TNF antagonists have been the mainstay in the treatment of inflammatory bowel diseases (IBD) for over 20 years (Vulliemoz et al, 2020), and the NFB pathway is known to be activated in inflamed colonic tissue from IBD patients (Atreya et al, 2008;Liu et al, 2017). It would be interesting for future studies to explore whether Th17 cells subset in cluster 0 is targeted by anti-TNF therapies in human IBD.…”

Section: Discussionmentioning

confidence: 99%

RORγt serine 182 tightly regulates T cell heterogeneity to maintain mucosal homeostasis and restrict tissue inflammation

Patel

Chen

et al. 2021

Preprint

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Unresolved inflammation causes tissue damage and contributes to autoimmune conditions. However, the molecules and mechanisms controlling T cell mediated inflammation remain to be fully elucidated. Here, we report an unexpected role of the RAR-Related Orphan Receptor-gamma protein (RORγt) in resolving tissue inflammation. Single-cell RNA-seq (scRNA-seq) revealed that an evolutionarily conserved serine 182 residue on ROR&γt (RORγtS182) is critical for restricting IL-1β-mediated Th17 activities and promoting anti-inflammatory cytokine IL-10 production in RORγt+ Treg cells in inflamed tissues. Phospho-null RORγtS182A knock-in mice experienced delayed recovery and succumbed to exacerbated diseases after dextran sulfate sodium (DSS) induced colitis and experimental autoimmune encephalomyelitis (EAE) challenge. Together, these results highlight the essential role of ROR&γtS182 in resolving T cell mediated tissue inflammation, providing a potential therapeutic target to combat autoimmune diseases.

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TNF-Alpha Blockers in Inflammatory Bowel Diseases: Practical Recommendations and a User’s Guide: An Update

Abstract: a on behalf of the Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology

Cited by 59 publications

References 87 publications

Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Therapeutic use of specific tumour necrosis factor inhibitors in inflammatory diseases including COVID-19

RORγt serine 182 tightly regulates T cell heterogeneity to maintain mucosal homeostasis and restrict tissue inflammation

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