Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy

Clinicians do not often employ washout periods before prescribing a change in therapy for rheumatoid arthritis (RA). As a result, the observed effectiveness or lack of effectiveness of a new drug actually represents the effectiveness of that drug had the patient been taking placebo minus the residual effectiveness of the old drug.

We studied new starts of selected disease modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA from 8 ARAMIS data bank centers, broken into subgroups on the basis of immediately prior therapy. Therefore, we examined the hypothesis that the chances of a treatment being observed effective depend upon the immediately preceding treatment. Using intent-to-treat analysis, we analyzed the effects upon Health Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months after the new drug start.

Methotrexate reduced disability significantly except after intramuscular gold or hydroxychloroquine and it reduced pain significantly after all prior therapies. Hydroxychloroquine reduced disability significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but disability increased after intramuscular gold; pain was decreased only after NSAID only. Prednisone had no consistent effect upon disability but was consistently associated with decreased pain. Greatest effectiveness was always seen with a new drug start after NSAID only treatment versus after DMARD treatment.

The effectiveness of a newly started RA treatment after 9 months may be substantially influenced by immediately prior treatment. This finding provides an additional reason for concern about direct extrapolation of clinical trial data into clinical practice.