In chronic rheumatoid arthritis (RA), disease modifying drugs are used in an attempt to suppress the progressive damage to tissues and joints that is associated with active disease. Their success in achieving this goal is variable; responses vary from complete suppression of all signs and symptoms of RA to continued active disease, with progressive disability, despite prolonged therapy. Because disease activity almost always recurs after the therapy is stopped, early interruption of an effective therapy for any reason will make its benefit insignificant in a lifelong disease such as RA. Similarly, short-term sequential use of multiple disease modifying therapies is unlikely to be beneficial. The immediate problems with these therapies are substantial. In general, fewer than 50% of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months or longer to achieve maximum effects, those patients who are unable to continue the drug receive little benefit from it. Inevitable delayed side-effects, such as those associated with chronic corticosteroid therapy, may make the benefit/risk ratio unacceptable. Potential late lethal adverse effects, such as malignancy, weight the benefit/risk ratio to varying extents for individual patients, depending on the relative probability that the adverse effect will occur during the remainder of the patient's anticipated life span, and are of greater importance in younger patients. In that minority of patients who achieve remission or near remission and are able to tolerate a disease modifying treatment for many years, it is of truly significant benefit. We are still searching for a therapy that will reliably achieve this goal for most patients with RA.
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