Can we discontinue synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis?

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 Individuals in whom DMARDs were withdrawn were three times more likely to have flares.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.