Among pharmacological treatments known to reduce disease activity in RA, disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and leflunomide, or biologic treatments, such as anti-TNF (infliximab, adalimumab, etanercept, golimumab and certolizumab), anti-IL-6 (tocilizumab), CTLA4 immunoglobulin (abatacept) and anti-CD20 (rituximab), have improved pain and mood disorders as well as fatigue, although the overall effect size of biotherapies on fatigue was small (effect size = 0.45; 95 % confidence interval 0.31 to 0.58) [4, 45, 46]. The gene discussed is CTLA4; the disease is rheumatoid arthritis.