Can rheumatoid arthritis ever cease to exist: a review of various therapeutic modalities to maintain drug-free remission?

Therapies for rheumatoid arthritis (RA) were mostly aimed at reducing the pain, stiffness and further progression of joint destruction. However, with the advent of biologic agents that act against specific inflammatory cytokines contributing to RA pathogenesis (treat-to-target strategy), the degree of remission achieved has been remarkably impressive. In particular, inhibition of tumor necrosis factor a (TNF alpha), interleukins-1 and -6 and receptor-activator of nuclear kappa B ligand by neutralizing antibodies in early diagnosed RA patients has resulted in lowering of disease activity to levels that enable them to function as in the pre-disease stage. There are other biologic approaches such as depletion of B cells and blocking T-cell co-stimulators that have been included successfully in RA therapy under the class of disease-modifying anti-rheumatic drugs (DMARD). Given the excellent clinical outcomes of biologic DMARDs when initiated early in RA, discontinuation or dose tapering is practised. Because biologic DMARDs are expensive and also known to make users vulnerable to viral infections, dose reduction and drug holiday are reasonable steps when sustained good clinical response has been achieved. Majority clinical studies have been done with TNF inhibitors and data suggest that sustained remission of RA is achieved in several multi-centric studies carried out worldwide. However, high flare rate and reappearance of disease has been reported in several cases. This review critically discusses response predictors of biologic DMARDs, the case for treatment relaxation, strategizing drug tapering considering patient eligibility and timing in light of available clinical practice guidelines of RA.