Predictors of Immunogenicity and Loss of Response to ANTI-TNFα Therapy in Crohn Disease—A Systematic Review

Background: As the use of anti-tumor necrosis factor-α (TNFα) therapies in Crohn disease (CD) is spread, the loss-of-response (LOR) to it is increasingly encountered. Discovering a pathological pathway and biomarkers that can predict LOR would assist in the management of patients with CD. In this article, we provide a comprehensive systematic review of studies assessing predictors of immunogenicity and loss-of-response to anti-TNFα drugs in patients with CD. Data sources: We performed a systematic review of PubMed to identify citations pertaining to predictors of immunogenicity and loss-of-response to anti-TNFα drugs in patients with CD through April 27, 2024, using a predefined string of keywords. Data extraction and quality assessment were performed independently by 2 reviewers. Results: A total of 18 eligible studies were included in the review. Four major groups of studies were identified: genetic factors, factors linked with colonic inflammation, serum and anthropological markers, and prevention of LOR. Promising predictors of LOR to infliximab or adalimumab include the carriage of HLA-DQA1*05, visceral adiposity, intestinal abundant presence of CD96, IL-17, and IL-23. Substantial heterogeneity was observed, and none of the markers had undergone formal validation. Specific limitations to acceptance of these factors included failure to use a standardized definition of LOR to anti-TNFα treatment, lack of specificity, and insufficient relevance to the pathogenesis of LOR. Conclusions: This review underlines the lack of well-defined studies and controlled trials investigating predictors of LOR to anti-TNFα therapies in CD. A research priority is the development of reliable and accurate biomarkers that can shed light on the pathogenesis of the implied LOR. These biomarkers, along with genetic factors, have the potential to enhance clinical management by aiding in patient stratification and monitoring.