Defining the Path Forward for Biomarkers to Address Unmet Needs in Inflammatory Bowel Diseases

Abstract

Despite major advances in the inflammatory bowel diseases field, biomarkers to enable personalized and effective management are inadequate. Disease course and treatment response are highly variable, with some patients experiencing mild disease progression, whereas other patients experience severe or complicated disease. Periodic endoscopy is performed to assess disease activity; as a result, it takes months to ascertain whether a treatment is having a positive impact on disease progression. Minimally invasive biomarkers for prognosis of disease course, prediction of treatment response, monitoring of disease activity, and accurate diagnosis based on improved disease phenotyping and classification could improve outcomes and accelerate the development of novel therapeutics. Rapidly developing technologies have great potential in this regard; however, the discovery, validation, and qualification of biomarkers will require partnerships including academia, industry, funders, and regulators. The Crohn's & Colitis Foundation launched the IBD Biomarker Summit to bring together key stakeholders to identify and prioritize critical unmet needs; prioritize promising technologies and consortium approaches to address these needs; and propose harmonization approaches to improve comparability of data across studies. Here, we summarize the outcomes of the 2018 and 2019 meetings, including consensus-based unmet needs in the clinical and drug development context. We highlight ongoing consortium efforts and promising technologies with the potential to address these needs in the near term. Finally, we summarize actionable recommendations for harmonization, including data collection tools for improved consistency in disease phenotyping; standardization of informed consenting; and development of guidelines for sample management and assay validation. Taken together, these outcomes demonstrate that there is an exceptional alignment of priorities across stakeholders for a coordinated effort to address unmet needs of patients with inflammatory bowel diseases through biomarker science.

Keywords: biomarker; harmonization; precision medicine; prognosis; treatment response.

FIGURE 1.

Biomarkers required to address unmet clinical needs in IBD. Prognostic biomarkers are needed to predict, early in the disease or at diagnosis, a quiescent or aggressive disease course characterized by continuous relapse, need for drug escalation, and development of penetrating and stricturing complications (left panel). Predictive biomarkers are required to identify, before treatment initiation, those patients likely to respond or not to drug treatment (center panel). Monitoring biomarkers are also needed to facilitate frequent and minimally invasive monitoring of patient response to treatment during drug trials and in clinical practice (right panel).

FIGURE 2.

Harmonization needs and approaches for IBD biomarker discovery and qualification. Unification of research procedures that facilitate comparisons across studies remains an outstanding challenge to advance IBD biomarker science. Three main approaches are proposed that, if implemented, could have a transformative impact on this field. First, general adoption of the IBD SmartForm would unify clinical parameters and measurements used in the clinic to phenotype patients (left panel). Second, implementation of a standard informed consent template would facilitate broad use of data, samples, and recontacting of subjects (middle panel). Third, generalized use of a biomarker readiness checklist that includes unified procedures, criteria, and measurements for sample collection, storage, and assay development would enhance data comparability and reproducibility (right panel).

FIGURE 3.

Path forward to IBD biomarker discovery and qualification. The end goal of the IBD biomarker field will be to enable precision medicine in clinical practice and effective clinical trials. This will be possible throughout a concerted effort among different stakeholders who will establish effective collaborations for biomarker discovery, validation, and qualification. These coalitions will utilize harmonized processes and data from real-world longitudinal cohorts, which will be critical for the identification of biomarkers with reproducible, generalizable, and enhanced performance in diverse IBD patient populations. Given the variety of biomarker needs in IBD, the implementation of diversified technological and analytical platforms, including machine learning, will be essential not only to identify novel biomarkers but also to define a gold-standard measurement that can be used as a comparator benchmark for novel biomarkers.