**5. Genetic Predictors of Response to Rheumatoid Arthritis Drug Therapy**

#### *5.1. Therapy of RA with the Use of Antirheumatic Drugs*

RA treatment aims to achieve clinical remission and minimal disease activity. The classes of drugs used in RA therapy are known under the common name disease-modifying antirheumatic drugs (DMARDs). Synthetic DMARDs are divided into conventional synthetic DMARDs (csDMARD, for example, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, and others) and targeted synthetic DMARDs (tsDMARD, for example, baricitinib, tofacitinib, upadacitinib). Biological DMARDs (bDMARDs) comprise the second group of drugs. bDMARDs may be subdivided into distinct classes depending on their targets: TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL6 inhibitors (sarilumab, tocilizumab), inhibitor of B-cells harboring CD20 (rituximab), and costimulating factors (abatacept). According to the recommendations of The European League Against Rheumatism (EULAR), updated in 2019, some basic rules should be followed in the treatment of RA. DMARD treatment should be started immediately after a diagnosis of RA. The first line of therapy uses methotrexate, which is the most widely used csDMARD. Methotrexate can be effective both in mono mode and in combination with other csDMARDs, tsDMARDs, and bDMARDs. If the patient has methotrexate intolerance, then leflunomide or sulfasalazine may be used instead. Glucocorticoids are prescribed only to a small number of patients for a short period in the first line of therapy. If during the first three months of treatment with methotrexate, there is no improvement, and clinical remission is not achieved after six months, then the second line of RA therapy should be used. In the absence of unfavourable prognosis factors (high levels of ACPAs, rheumatoid factor, high activity of the disease according to clinical scales and early damage to joints, ineffective use of two csDMARDs), another csDMARD is added to methotrexate. Another possible option is to replace methotrexate with another csDMARD. In the presence of unfavourable prognostic factors, bDMARDs or JAK inhibitors may be used instead of methotrexate. If after some time (for example, three months), it is not possible to achieve an improvement in the condition and clinical remission, then another bDMARD is prescribed as a third-line drug. If remission is achieved as a result of using any of the described lines of therapy, the dose of DMARD is reduced and the optimal period of visits to the rheumatologist is established to control the activity of the disease [65]. Similar recommendations for the treatment of RA were previously published by the American College of Rheumatology (ACR) [66]. It should be noted that maybe in the future, the characteristics of the patient's genome would determine the sensitivity and resistance to various DMARDs.
