How and when should combination therapy be used? The role of an anchor drug.

Most patients with rheumatoid arthritis do not achieve a complete response to monotherapy; some achieve a sub-optimal response and others become resistant to therapy and escape from control after an initial good response. It is essential to recognize those with an incomplete response early and to introduce combination therapy promptly so as to induce remission and minimize joint damage and disability. The main concern about combination therapy has been the risk of additive or synergistic toxicity. The aim is therefore to choose drugs that are the least toxic and that also have a rapid and sustained action. Sulphasalazine (SASP) possesses these properties; it has a mild toxicity profile and good long-term tolerability. Most adverse events occur during the first few months of therapy and accumulative toxicity on stable maintenance doses is rare. It also has a rapid onset of action and sustained efficacy. On these grounds we recommend that SASP is used in combination therapy as the 'anchor drug' to which other drug(s) can be added sequentially. This sequential regimen allows those patients who respond to monotherapy to be identified, and gives flexibility of dose control so that the drugs can be tailored to the individual patient. Combination therapy may have real advantages in inducing remission and preventing resistance to therapy. it also has the potential for long-term disease modification.