Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

Targeting IL12/23 in ulcerative colitis: update on the role of ustekinumab

“…Drug-specific validated markers to predict the response to therapy are impressively absent: a multiparametric predictive model incorporating genetic, clinical, immunological, microbiological, and pharmacokinetic markers seems the most promising tool, but its feasibility in clinical practice is still inadequate. 73 To date, the choice among different MoA – with the notable exception of pharmacokinetic failures to anti-TNF-α therapy 74 – is empirical and guided by physicians’ personal experience and confidence, hospital facilities and setting, pharmacoeconomic considerations, and patient’s preference. Ustekinumab could potentially exhibit several advantages over other competitors in UC (anti-TNF-α drugs, vedolizumab, and tofacitinib), including a favorable profile of safety, effectiveness on certain extraintestinal manifestations, and a convenient administration mode (q12w or q8w subcutaneous injection).…”

Predictive approaches in inflammatory bowel disease

“…1 IBDs are multifacets and multi-omics diseases. 2 Different features contribute to responsiveness to treatments and would need to be carefully considered in parametric predictive models. The immune system presents some plasticity, and one clinical phenotype can activate different inflammatory pathways and respond differently to therapies.…”

“…Current data suggest that CD is a multiple entity—inflammation is not homogeneous along the colon—and that interleukins pathways and mechanisms of action of potential treatments implicate several tissue layers. 1 , 2 , 3 …”

Coriolus Versicolor Downregulates TLR4/NF-κB Signaling Cascade in Dinitrobenzenesulfonic Acid-Treated Mice: A Possible Mechanism for the Anti-Colitis Effect

“…There is currently no cure for ulcerative colitis or Crohn’s disease. Most existing treatments aim to relieve symptoms and prevent them from returning and include specific diets, lifestyle changes, medications (sulfasalazine; corticosteroids; immunosuppressive agents; and several biologics, for example anti-TNF-α antibodies) and, in the most serious cases, surgery [ 11 , 12 , 13 , 14 ].…”