Response to MTX-based therapy can be determined after 3 to 6 months according to changes in disease activity score 28 (DAS28) and insufficient responders require step-up treatment with biologic disease modifying anti rheumatic drugs (bDMARDs; e.g., TNF-alpha inhibitors, IL-6 inhibitors [6]) or targeted synthetic DMARDs (tsDMARDs, e.g., Janus-kinase inhibitors [7,8]) as described in the EULAR recommendations for the management of RA [2]. The gene discussed is TNF; the disease is rheumatoid arthritis.