Testing for a unique genetic signature through a blood test can predict nonresponse to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis, suggests a new observational study published in the journal Rheumatology and Therapy.

The molecular signature response classifier (MSRC) test was assessed in the multicenter, prospective, observational NETWORK-004 study in 391 patients who were therapy-naïve and 113 patients who were given TNF inhibitors. The primary outcome measure was the improvement seen at 6 months, according to American College of Rheumatology (ACR) response criteria (ACR50).

Results showed that the test could identify patients who were unlikely to respond well to treatment with TNF inhibitors.

Forty-five percent of the treatment naïve patients showed the molecular signature of non-response with the area under the curve (AUC) of 0.64. These patients had less probability of responding adequately to TNF inhibitors at 6 months, as per ACR 50. The AUC was up to 0.83 in patients who had been treated with TNF inhibitors with odds ratios of 3.3–26.6 by ACR.

The molecular signature test includes 23-features: 19 biomarkers (RNA transcripts) and 4 clinical features (body mass index, gender, patient global assessment and anticyclic citrullinated protein [anti-CCP] serostatus).

Patients who score high on the MSRC test will not respond well to TNF inhibitors in all probability and hence are also less likely to achieve disease remission. If the score is low, chances of adequate response also increase.

Treatment-naïve patients who showed a molecular signature of non-response were 3 to 9 times less likely to have an adequate response to TNF inhibitors. Conversely, in patients who had been on TNF inhibitors, a molecular signature of non-response was associated with 26 times less chances of response to treatment.

Although the predictive ability was much less than 100%, this test has the potential to be practice changing as a guide to rheumatologists in selection of treatment for rheumatoid arthritis patients. Patients who do not have this signature can be prescribed TNF inhibitors with better chances of achieving disease remission.

Reference: Cohen S, et al. A molecular signature response classifier to predict inadequate response to tumor necrosis factor-α inhibitors: The NETWORK-004 prospective observational study. Rheumatol Ther. 2021;8(3):1159-1176.

Prof Dr S. Ramakrishnan,

(Emeritus Prof.) The Tamil Nadu Dr. M.G.R. Medical University; 

Senior Consultant Rheumatologist, Apollo Hospitals Chennai