Targeted Therapies - Many Ways to (the Peace of) Rome

Rheumatoid arthritis (RA) is a chronic autoimmune disease that destroys joints and, if not appropriately controlled, severely limits life expectancy and quality of life. Such control can be achieved, even though cure is impossible for the time being. The mainstay of RA therapy are conventional disease-modifying drugs, (DMARDs), such as low dose methotrexate, sulfasalazine, and leflunomide, which should be started not later than 12 weeks after the onset of symptoms. Since these DMARDS need at least 6 weeks to control disease, the time interval is commonly bridged with corticosteroids. TNF blockers at this very early stage may be even more effective, but long-term impact of such therapy will yet have to be established. If, however, conventional DMARDs fail to achieve remission (or at least low disease activity), TNF blockade in combination with methotrexate is indicated and has a high rate of success, which extends to blocking erosions even in patients who still have active disease. At present, there are three TNF blockers (infliximab, etanercept, adalimumab) available, and two will be added shortly (certolizumab pegol, golimumab). If a first TNF blocker is not successful, other TNF blocking agents may still work. Alternatively, depletion of B cells with rituximab or costimulation blockade with abatacept, both in combination with methotrexate, are successful routine for many patients today, and interleukin-6 receptor blockade with tocilizumab will join this group shortly. Enforced peace thus is feasible for the vast majority of RA patients, but better understanding of RA pathophysiology and additional drugs are still needed.