Method for predicting the response to tnf inhibitors

Rheumatoid arthritis (RA) is the most prevalent chronic autoimmune inflammatory rheumatism. Its pathophysiology is largely dependent on TNF. Severe RA as well as several other inflammatory and autoimmune diseases are treated with TNF inhibitors (TNFi). However, to date only 30-50% achieve low disease activity or remission with this treatment regimen and some patients experience secondary non-response or relapse. Herein, the inventors evaluated by RT-qPCR the mRNA expression of CD36, which was already described to be regulated by TNFi5, some specific NRF2 target genes (FBX030, GABARA, LBR, MAFG, OSGIN1, HMOX1), which play a role in the anti-oxidative stress response or anti-inflammatory pathway, and the expression of CSMD1, an anti-inflammatory gene that we observed as up-regulated by all TNFi. Interestingly, they observed 2 different subsets of healthy donors: (i) donors in which TNFi stimulation increased mRNA of target genes in macrophages and (ii) conversely donors with no significant upregulation in transcription of these target genes. Then they classified donors two different status, “activators” or “non-activators” of tmTNF reverse signaling after TNFi stimulation, which correlates to clinically responder and non-responders to TNFi. Thus, based on all these observations, they developed an in vitro method for predicting the response to TNF inhibitors in patient in need thereof.

Keywords: Treatment Response Prediction, Rhumatoid Arthritis, TNFinhibitor treatments, CD36
Patent Application number: EP20 306 247.6 on 20/10/2020
PCT/EP2021/078973 on 19/10/2021

You might also be interested in