Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF

Viazis, Nikos; Giakoumis, Marios; Bamias, Giorgos; Goukos, Dimitris; Koukouratos, Theodoros; Katopodi, Konstantina; Triantos, Christos; Tsolias, Chrisostomos; Theocharis, Georgios; Daikos, George L.; Ladas, Spyros D.; Karamanolis, Dimitrios G.; Mantzaris, Gerasimos

doi:10.1016/j.dld.2016.10.008

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…In a study with UC patients, mucosal healing upon initiated anti-TNF therapy was associated with lower pre-treatment mucosal expression of transcription factor Th1-Tbet and higher expression of Th17-Rorc ( 124 ) in primary responders. Furthermore, GATA3 expressing lamina propria CD4+ T lymphocytes were increased in anti-TNF endoscopic primary non-responders compared to responders in CD patients ( 120 ).…”

Section: Tissue Markersmentioning

confidence: 99%

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

2020

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The advent of anti-TNF agents as the first approved targeted therapy in the treatment of inflammatory bowel disease (IBD) patients has made a major impact on our existing therapeutic algorithms. They have not only been approved for induction and maintenance treatment in IBD patients, but have also enabled us to define and achieve novel therapeutic outcomes, such as combination of clinical symptom control and endoscopic remission, as well as mucosal healing. Nevertheless, approximately one third of treated patients do not respond to initiated anti-TNF therapy and these treatments are associated with sometimes severe systemic side-effects. There is therefore the currently unmet clinical need do establish predictive markers of response to identify the subgroup of IBD patients, that have a heightened probability of response. There have so far been approaches from different fields of IBD research, to descry markers that would empower us to apply TNF-inhibitors in a more rational manner. These markers encompass findings from disease-related and clinical factors, pharmacokinetics, biochemical markers, blood and stool derived parameters, pharmacogenomics, microbial species, metabolic compounds, and mucosal factors. Furthermore, changes in the intestinal immune cell composition in response to therapeutic pressure of anti-TNF treatment have recently been implicated in the process of molecular resistance to these drugs. Insights into factors that determine resistance to anti-TNF therapy give reasonable hope, that a more targeted approach can then be utilized in these non-responders. Here, IL-23 could be identified as one of the key factors determining resistance to TNF-inhibitors. Growing insights into the molecular mechanism of action of TNF-inhibitors might also enable us to derive critical molecular markers that not only mediate the clinical effects of anti-TNF therapy, but which level of expression might also correlate with its therapeutic efficacy. In this narrative review, we present an overview of currently identified possible predictive markers for successful anti-TNF therapy and discuss identified molecular pathways that drive resistance to these substances. We will also point out the necessity and difficulty of developing and validating a diagnostic marker concerning clinically relevant outcome parameters, before they can finally enter daily clinical practice and enable a more personalized therapeutic approach.

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Section: Tissue Markersmentioning

confidence: 99%

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

2020

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“…A total of 10 638 citations were identified from the electronic and manual search. After removing duplicates (n = 767) and non‐applicable references (n = 9620), 251 citations were screened, of which 92 met the inclusion criteria (Figure ) . Baseline characteristics of the included manuscripts, study quality and studies reporting negative results are provided in Table S1, S2 and S3 respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Baseline characteristics of the included manuscripts, study quality and studies reporting negative results are provided in Table S1, S2 and S3 respectively. Data from several included studies are only presented in tables . Figures and provide an overview of different predictive molecular markers grouped by underlying biological mechanism.…”

Section: Resultsmentioning

confidence: 99%

Systematic review: predictive biomarkers of therapeutic response in inflammatory bowel disease—personalised medicine in its infancy

Stevens

Matheeuwsen

Lönnkvist

et al. 2018

Aliment Pharmacol Ther

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Summary Background Inflammatory bowel disease (IBD) is characterised by substantial heterogeneity in treatment response. With an expanding number of therapeutic agents, identifying optimal treatment at the patient level remains a major challenge. Aim To systematically review the available literature on predictive biomarkers of therapeutic response in IBD. Methods An electronic literature search was performed on 30 January 2018 using MEDLINE, EMBASE and the Cochrane Library. Retrospective, prospective, uncontrolled and controlled studies reporting on biomarkers predicting therapeutic response in paediatric and adult IBD populations were eligible for inclusion. The methodological quality of the included studies was assessed using the QUIPS tool. Due to anticipated heterogeneity and limited data, a qualitative, rather than quantitative, assessment was planned. Results Of the 10 638 citations identified, 92 articles met the inclusion criteria. Several potential DNA, mRNA and protein markers were evaluated as predictive biomarkers. Most studies focused on predicting response to anti‐TNF agents. Substantial between‐study heterogeneity was identified with respect to both the biomarkers studied and the definition of response. None of the included studies received a low risk of bias rating for all six domains. Currently, none of the biomarkers is sufficiently predictive for clinical use. Conclusions The search for predictive biomarkers is still in its infancy and current evidence is limited. Future research efforts should take into account the high patient heterogeneity within prospective trials with objective response assessment. Predictive models will most likely comprise a combination of several molecular markers from integrated omics‐levels and clinical characteristics.

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“…Several studies have evaluated the effectiveness of combining IFX with IM in patients with moderate-to-severe UC ( 7 , 8 ). However, the effectiveness of combining ADA with IM is unclear ( 9 - 13 ). A retrospective analysis of large cohort by Chen et al demonstrated that combination therapy using IM can increase the persistence of biologic treatments including ADA ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of the Concomitant Use of Immunomodulator and a Lower Week 8 Partial Mayo Score on the Persistence of Adalimumab in Refractory Ulcerative Colitis

Kumei

Sakurai

So³

et al. 2021

Intern. Med.

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Objective Real-world data of adalimumab (ADA) in the treatment of ulcerative colitis (UC) are scarce. We aimed to study the ADA response rates and predictors of response in UC treatment. Methods This observational, prospective and multi-center study assessed the clinical outcome of refractory UC patients treated with ADA who previously had an inadequate response to either conventional therapies or other anti-TNF antibodies or tacrolimus. The primary endpoint was the proportion of UC patients achieving a clinical response and remission at 8 and 52 weeks. We also evaluated the parameters which were associated with a clinical response at 8 and 52 weeks. Results A total of 35 patients were enrolled from 11 centers. The clinical responses at 8 and 52 weeks were 60.0% and 51.4%, respectively. The clinical remission rates at 8 and 52 weeks were 45.7% and 48.6%, respectively. Positive predictors for week 52 response were combination of ADA with immunomodulator (IM) (OR: 27.229; 95% CI; 1.897-390.76; p=0.015) and a week 8 lower partial Mayo score (OR: 0.406; 95% CI; 0.204-0.809; p=0.010). A receiver operation characteristic curve analysis revealed the optimal week 8 partial Mayo score to be 2.5, therefore a partial Mayo score of ! 2 was a positive predictor for the continuation of ADA. No malignancy or death occurred during this study. Conclusion ADA was effective for inducing and maintaining both a clinical response and remission in patients with refractory UC. It remains possible that the concomitant use of IM and a week 8 partial Mayo score of ! 2 may predict the long-term response of ADA.

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Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF

Cited by 8 publications

References 35 publications

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

Systematic review: predictive biomarkers of therapeutic response in inflammatory bowel disease—personalised medicine in its infancy

Impact of the Concomitant Use of Immunomodulator and a Lower Week 8 Partial Mayo Score on the Persistence of Adalimumab in Refractory Ulcerative Colitis

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