Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease

Tumor necrosis factor (TNF) α is a major proinflammatory cytokine involved in the immune response in inflammatory bowel disease (IBD). Anti-TNF drugs such as infliximab and adalimumab are used to treat IBD; however, approximately 30% of patients do not respond to treatment. Individual genetic differences could contribute to lack of efficacy. Genetic studies have tried to uncover the factors underlying differences in response, however, knowledge remains limited, and the results obtained should be validated, so that pharmacogenetic information can be applied in clinical practice. In this review, we gather current knowledge in the pharmacogenetics of anti-TNF drugs in patients with IBD. We observed a connection between the major genes described as possible predictors of response to anti-TNF drugs in IBD and the cytokines and molecules involved in the T helper (Th) 17 pathway.     

Validation Study of a New Random-Access Chemiluminescence Immunoassay Analyzer i-TRACK10® to Monitor Infliximab and Adalimumab Serum trough Levels and Anti-Drug Antibodies

Background. Monitoring of biological TNF inhibitors is a very important tool to guide clinical decisions using specialized algorithms, especially in gastroenterology. A new chemiluminescent instrument (i-TRACK^10® from Theradiag) could replace ELISA techniques to calculate the dosage of drugs and anti-drug antibodies. In this bi-centric study, we explored the analytical performances of i-TRACK^10® using manual or automated (DS2^®) ELISA Lisa-Tracker^® assays, and compared the results. Patients and methods. Intra- and inter-run performances were evaluated with i-TRACK^10® in two different laboratories and for two different ranges of values for infliximab, adalimumab, and their respective antibodies. Patients’ samples were used in the labs to compare the results obtained between the new instrument and either the manual Lisa-Tracker^® or the automated DS2. Results. Intra- and inter-run performances were satisfactory, with values between 1.8% and 16.1% (for inter-run imprecision at low/medium values of infliximab). Results were generally comparable between assays. with the lowest value of correlation at 0.59 (anti-adalimumab dosage between i-TRACK^10® and manual ELISA). Most often, values of drugs and anti-drug antibodies were higher with i-TRACK^10® than with manual ELISA assay, and correlation values were better with automated ELISA. Agreements were globally acceptable, and the lowest coefficients of 0.7 was obtained for adalimumab values between i-TRACK^10® and the two ELISA methods, and for anti-adalimumab values between i-TRACK^10® and manual ELISA. The type of assay can potentially induce a change in the class of patients and lead to divergent therapeutic decisions. Conclusions. The new random-access instrument i-TRACK^10® presents many advantages in a routine laboratory: rapidity, the possibility of standardization, usability, and expansion of the measurement range. Despite the relatively good agreement of results, it is preferable to use the same assay in longitudinal follow-up of a patient, because quantitative results were not completely equivalent especially for anti-drug antibodies.