Biomarker discovery for personalized therapy selection in inflammatory bowel diseases: Challenges and promises

Abstract

The past decades witnessed a significant stride in deciphering the pathophysiology of inflammatory bowel disease, which further advanced drug development adding several new biologicals and small molecules to the arsenal of available therapies. Surprisingly, this wealth in therapeutic options did not yield the aspired high durable response rates. In addition, the increase in therapeutic availabilities ignited an increase in research toward biomarkers that could help assign therapies to patients with the highest probability of response. Luckily, major steps have been undertaken in this domain which resulted in the discovery of some interesting biomarkers that are still under validation. However, the pace in which this domain is progressing, the discordance between short-term endpoints in biomarker discovery studies and the ambition of the disease community in modifying disease course, and the uncertainties about the validity of discovered biomarkers highlight the need for a critical appraisal of research conduct in this domain. In this review, we shed light on areas of improvement in biomarker discovery studies that will help optimize the use of available therapies and break the current therapeutic ceiling.

Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

“…First, the discovery of robust PD biomarkers will help avoid the inconvenience and costs of monitoring and dosing adjustments, which would be futile in patients with non-TNF-driven disease. 81 Second, the practicality and benefits of pharmacogenomics in guiding precision dosing still need to be investigated in prospective studies. Third, extensive profiling of infliximab clearance and exposure should be conducted in groups with distinct patient and disease characteristics, such as children, elderly patients, those with extensive disease involvement, longstanding disease, and especially patients with reported lower response rates to infliximab.…”

“…Understanding the relationship between infliximab exposure, PK parameters, and PD biomarkers may facilitate the identification of patients with mechanistic nonresponsiveness, for whom infliximab monitoring and dosing adjustments should be avoided. 81 Although one most recent TC of infliximab sufficed for accurate and precise Bayesian forecasting in a retrospective evaluation, 169 more research is still required to identify optimal sampling regimens resulting in the most accurate Bayesian forecasting. Finally, an SC formulation of infliximab was recently added to the armamentarium for maintenance treatment in patients with chronic inflammatory disease.…”

Advances in Inflammatory Bowel Disease Diagnostics: Machine Learning and Genomic Profiling Reveal Key Biomarkers for Early Detection

“…These datasets Diagnostics 2024, 14, 1182 2 of 26 offer insights for identifying diagnostic biomarkers to distinguish IBD patients from healthy individuals [4]. However, analyzing high-dimensional low-sample size (HDLSS) transcriptomic data remains challenging [5,6]. Machine learning (ML) techniques have emerged as powerful tools for analyzing complex biological datasets and discovering predictive patterns [7][8][9].…”

Clinical value of multi-omics-based biomarker signatures in inflammatory bowel diseases: challenges and opportunities

“…First, an important but often overlooked aspect is the use of concomitant medication. A striking example includes corticosteroids, which may confound biomarker discovery mainly because of their inherently strong anti-inflammatory effects, which may affect disease activity and therapeutic response ( 26 ). Although it remains difficult to pinpoint the exact effects on certain molecules, medication usage may result in inaccurate biomarker evaluation.…”