Molecular signature-assisted drug selection helps in improving therapeutic response in RA

A recent study published in the Expert Opinion on Biological Therapy has highlighted that RA treatment selection based on molecular signature response classifier (MSRC) test helps in in improving the therapeutic outcomes in real-world settings.

The interim analysis carried out by Strand et al. gathered the data of RA patients who received the blood-based MSRC test. The study endpoints considered were the absolute changes in clinical disease activity index (CDAI) scores from baseline at 12 weeks (n = 470) and 24 weeks (n = 274). Predicted TNFi non-responders who received a biologic or targeted synthetic DMARDS with an alternative mechanism of action demonstrated 1.8-fold significant improvements in CDAI scores as opposed to those treated with a TNFi (12 weeks: 12.2 vs 8.0; P 0.083; 24 weeks: 14.2 vs 7.8; P 0.009).  Upon treating likely TNFi non-responders with a non-TNFi therapy, 43.2% relative improvement in attaining a lower CDAI disease activity (38.9% vs 55.7%) was observed.

The MSRC test kit comprises of two PAXgene Blood RNA Tubes for gene expression analysis and one serum separator tube for anti-CCP testing. The blood-based MSRC helps in treatment initiation, switching, or dose escalation of TNFi therapy.  It also assists in considering alternative b/tsDMARD treatment upon detection of a molecular signature of non-response to TNFi. The test has been clinically validated to predict non-response based on various response outcome criteria such as ACR50, DAS28-CRP and CDAI.

According to Sam Asgarian, chief medical officer of Scipher Medicine and co-author of the current study, “Blood tests that reveal a person’s unique molecular disease signature and match it to the most effective existing therapy are clinically valuable and make a significant impact on patient treatment outcomes.”

 Reference: Strand V, Zhang L, Arnaud A, Connolly-Strong E, Asgarian S, Withers JB. Improvement in clinical disease activity index when treatment selection is informed by the tumor necrosis factor-ɑ inhibitor molecular signature response classifier: analysis from the study to accelerate information of molecular signatures in rheumatoid arthritis. Expert Opin Biol Ther. 2022;22(6):801-807.