Flare during drug withdrawal as a method to support efficacy in rheumatoid arthritis: amiprilose hydrochloride as an example in a double blind, randomized study.

OBJECTIVE

To evaluate the use of a randomized, double blind, drug withdrawal design as a means to test the efficacy of longterm therapy with antirheumatic drugs.

METHODS

We evaluated 286 patients with rheumatoid arthritis (RA) treated with amiprilose hydrochloride for 1-3 years, with response, with or without other antirheumatic therapy, in a double blind, 12 week withdrawal study that compared patients randomized to continue amiprilose therapy vs patients randomized to placebo. The primary efficacy variable was preventing a predefined degree of clinical reactivation, or flare; the statistical tests of success were a difference in the proportion of flares and in the mean time to flare.

RESULTS

Thirty percent of patients taking amiprilose and 43% of placebo patients experienced flare (p = 0.026). Patients taking amiprilose had a longer flare-free interval compared to placebo patients (p = 0.027), with the time to reactivation or flare becoming statistically different 73 days after withdrawal.

CONCLUSION

Placebo controlled withdrawal designs are useful as evidence to support the longterm effectiveness of therapy in a proportion of patients with RA.