Biomarkers for prediction of TNFalpha blockers response in rheumatoid arthritis.
Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that plays pivotal roles in regulating the inflammatory response in rheumatoid arthritis (RA). Intensive studies on TNFalpha-driven inflammation processes have led to the development of TNFalpha blockers for RA treatment. However, response to these therapies is heterogeneous with roughly two-thirds of patient response and one-third non-response. Given the destructive nature of RA, the risk of adverse effects, and considerable costs for TNFalpha blocker therapy, there is a strong need to identify predictors of response prior to start the TNFalpha blocker therapy. Here we review several studies focused on predicting the response to TNFalpha blockers. Demographic, clinical, radiological, blood, genetic or synovial tissue biomarkers were studied to find some predictive biomarkers of TNFalpha blocker response. Unfortunately, results from these studies are heterogeneous. Discrepancy between these studies can be explained in part to the heterogeneity between the studies. As difference in the response criteria used, the delay of efficacy for the primary endpoint, and the genetic background of each population were all observed. Nevertheless, a high local and systemic level of TNFalpha prior to TNFalpha blocker therapy seems to be associated with a good clinical response. However, to validate these results, additional studies using independent and large cohorts are needed.
Marotte
Hubert
H
Clinical Immunology Unit, Departments of Immunology and Rheumatology, Edouard Herriot Hospital, 69437 Lyon cedex 03, France. hubert.marotte@laposte.net
Miossec
Pierre
P
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D011237:Predictive Value of Tests; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept