Effectiveness and toxicity considerations in outcome directed therapy in rheumatoid arthritis.

New paradigms of disease modifying antirheumatic drug based treatment strategies for rheumatoid arthritis (RA) raise new questions of sequencing of medications and employment of combination therapy. A broader view of chronic illness indicates that nonbiologic and self-management factors influence disease course and necessitate inclusion of patient oriented outcome measures such as disability and pain. I discuss these and related issues, present a broad model of disease progression in RA, introduce the concept of the "therapeutic segment," describe the dependence of clinical results on immediately prior therapy, and suggest a new research approach into the merits of combination therapy. Effectiveness is not necessarily increased by addition of a 2nd drug, nor is toxicity necessarily increased by combination therapy.