SYSTEMATIC REVIEW
Systematic review: predictive biomarkers of therapeutic response in inflammatory bowel disease—personalised medicine in its infancy
Toer W. Stevens,
Mijntje Matheeuwsen,
Maria H. Lönnkvist,
Claire E. Parker,
Manon E. Wildenberg,
Krisztina B. Gecse,
Geert R. D’Haens,
Toer W. Stevens
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMijntje Matheeuwsen
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMaria H. Lönnkvist
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorClaire E. Parker
Robarts Clinical Trials Inc, London, ON, Canada
Search for more papers by this authorManon E. Wildenberg
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Amsterdam, The Netherlands
Search for more papers by this authorKrisztina B. Gecse
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Geert R. D’Haens
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Correspondence
Prof. Dr. Geert R. D’Haens, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Email: [email protected]
Search for more papers by this authorToer W. Stevens,
Mijntje Matheeuwsen,
Maria H. Lönnkvist,
Claire E. Parker,
Manon E. Wildenberg,
Krisztina B. Gecse,
Geert R. D’Haens,
Toer W. Stevens
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMijntje Matheeuwsen
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMaria H. Lönnkvist
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorClaire E. Parker
Robarts Clinical Trials Inc, London, ON, Canada
Search for more papers by this authorManon E. Wildenberg
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Amsterdam, The Netherlands
Search for more papers by this authorKrisztina B. Gecse
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Geert R. D’Haens
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Correspondence
Prof. Dr. Geert R. D’Haens, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Email: [email protected]
Search for more papers by this authorThe Handling Editor for this article was Professor Jonathan Rhodes, and this uncommissioned review was accepted for publication after full peer-review.
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.
Supporting Information
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