OBJECTIVES: When rheumatoid arthritis (RA) patients have achieved sustained good 
clinical responses can their disease-modifying anti-rheumatic drugs (DMARDs) be 
reduced or discontinued? This review addresses this question by summarising the 
clinical evidence about DMARD withdrawal. It includes an assessment of 
predictive factors for sustained DMARD-free remissions.
METHODS: We evaluated the evidence for discontinuing DMARDs in stable RA in both 
randomised controlled trials (RCTs) and observational studies.
RESULTS: Six RCTs evaluated DMARD monotherapy withdrawal in 501 RA patients with 
good clinical responses. Flares occurred in 43/248 (17%) patients who continued 
DMARD monotherapy and in 117/253 (46%) patients who discontinued DMARDs. 
Individuals in whom DMARDs were withdrawn were three times more likely to have 
flares. Restarting DMARDs post-flare was usually successful. Four RCTs evaluated 
step-down DMARD combinations in comparison to DMARD monotherapy. Patients 
achieved good clinical responses with combination DMARDs, which were maintained 
after treatment was tapered to DMARD monotherapy. Four observational studies of 
tapering or stopping DMARDs in patients with sustained low disease activity 
states provided supportive evidence for discontinuing DMARDs in some patients. 
Flares during drug-free remissions were predicted by rheumatoid factor and 
anti-citrullinated protein antibody status.
CONCLUSIONS: Drug-free remission is achievable in some RA patients. 
Discontinuation of DMARDs after patients achieve sustained remissions results in 
flares in many patients, which can usually be reversed by restarting DMARDs. 
Step-down DMARD combinations are effective and achieve sustained responses. 
Further research is required to establish predictors of drug-free remission; 
these will identify individuals most likely to benefit or experience disease 
flares after discontinuing DMARDs.