Predicting and overcoming non-response to biologic therapies in immune-mediated diseases

Biologic therapies have reshaped the treatment of immune-mediated diseases across rheumatology, gastroenterology, dermatology, and respiratory medicine. TNF inhibitors, IL-17 and IL-23 antagonists, B-cell depleting agents, type 2 cytokine-targeted biologics for severe asthma, and small-molecule JAK inhibitors have delivered meaningful gains in disease control and patient quality of life. Yet a substantial proportion of patients fail to benefit. Primary non-response is reported in 20-40% of patients depending on the indication, and secondary loss of response over time affects many initial responders. The mechanisms are heterogeneous and include immunogenicity, pharmacokinetic variability, pathway redundancy, host genetic background, and underlying disease endotype. Despite a growing armamentarium, the ability to predict who will respond, and to rescue or reroute non-responders, remains a major unmet clinical need with direct consequences for patient outcomes and healthcare costs.This Research Topic aims to advance the understanding of why some patients fail to respond to biologic therapies in immune-mediated diseases, and what can be done to predict and overcome non-response. We welcome contributions across disease areas including inflammatory bowel disease, rheumatoid arthritis and other inflammatory arthropathies, psoriasis, severe asthma, atopic dermatitis, systemic lupus erythematosus, and connective tissue diseases. By bringing together perspectives from multiple specialties, this collection seeks to accelerate the translation of mechanistic insight into clinically actionable tools for personalized biologic selection.Original research, reviews, mini-reviews, and clinical or methodological perspectives are welcome. Themes and topics of interest include:• Biomarkers predicting primary and secondary non-response to specific biologic classes (TNF inhibitors, IL-17/23 antagonists, JAK inhibitors, anti-IL-5/IL-4Rα/IgE, anti-CD20, anti-BAFF, and others)• Immunogenicity and the clinical impact of anti-drug antibodies• Therapeutic drug monitoring and pharmacokinetic-driven treatment optimization• Mechanisms of pathway redundancy and immune escape in chronic immune-mediated disease• Switching strategies between biologic classes and within-class sequencing• Combination biologic and biologic-plus-small-molecule approaches• Endotype-driven patient stratification and precision medicine frameworks• Machine learning and multi-omics integration for response prediction• Cross-disease comparisons of response determinants• Health economic and real-world evidence on non-response and treatment switchingDr. James Schofield is the founder and CEO of TopMD Precision Medicine Ltd. The other Topic Editors declare no conflicting interests with this Research Topic. Topic editors: James Schofield, Ratko Djukanovic Source: https://www.frontiersin.org/research-topics/82565/predicting-and-overcoming-non-response-to-biologic-therapies-in-immune-mediated-diseases