A new assay accurately measures how arthritis patients respond to treatment with the arthritis drug adalimumab, a finding that highlights potential strategies for predicting the drug's effectiveness in patients. Rheumatoid arthritis (RA), a chronic disease characterized by painful joint inflammation, affects 54.4 million adults in the U.S and is a leading cause of disability worldwide. The disease can be treated with drugs that inhibit tumor necrosis factor (TNF), a protein involved in inflammation. However, treatment responses vary between patients, and efforts to understand how TNF promotes RA have been complicated by the difficulty of accurately measuring TNF concentrations in patients undergoing TNF inhibition. Here, Lea Berkhout et al. created a "drug-tolerant" assay that quantifies TNF concentrations during TNF inhibition with adalimumab, a commonly prescribed TNF inhibitor. The authors then analyzed samples from 193 RA patients who were treated with adalimumab and found the amounts of TNF circulating in the blood increased 50-fold during the first six months of treatment before reaching a stable concentration. A similar effect was observed in 30 volunteers who received one dose of adalimumab, indicating circulating TNF concentrations were not associated with disease activity during treatment. Furthermore, lower concentrations of TNF after the fourth week of treatment were associated with more antibodies against the drug and a lower chance of remission after 52 weeks. The authors say that early TNF concentrations could be used as a predictor of future patient responses, but call for further studies with longer follow-up periods.
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Journal
Science Translational Medicine