The molecular signature response classifier (MSRC) is a blood-based precision medicine test that predicts non-responders to tumor necrosis factor-ɑ inhibitors (TNFi) in rheumatoid arthritis (RA) so that patients with a molecular signature of non-response to TNFi can be directed to a treatment with an alternative mechanism of action. This study evaluated decision choice and treatment outcomes resulting from MSRC-informed treatment selection within a real-world cohort. Therapy selection by

more »

... rs was informed by MSRC results for 73.5% (277/377) of patients. When MSRC results were not incorporated into decision-making, 62.0% (62/100) of providers reported deviating from test recommendations due to insurance-related restrictions. The 24-week ACR50 responses in patients prescribed a therapy in alignment with MSRC results were 39.6%. Patients with a molecular signature of non-response had significantly improved responses to non-TNFi therapies compared with TNFi therapies (ACR50 34.8% vs 10.3%, p-value=0.05). This indicates that predicted non-responders to TNFi therapies are not non-responders to other classes of RA targeted therapy. Significant changes were also observed for CDAI, ACR20, ACR70, and for responses at 12-weeks. Adoption of the MSRC into patient care could fundamentally shift treatment paradigms in RA, resulting in substantial improvements in real-world treatment outcomes.