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Novel targeted therapies: the future of rheumatoid arthritis? Mavrilumab and tabalumab as examples

Rheumatoid arthritis (RA) control and outcome has greatly improved with the efficacy of biologic disease-modifying antirheumatic drugs (DMARDs)1 combined with early effective management and treatment targeting remission or low disease activity.2 ,3

However, although biologic therapy-blocking key molecules involved in the pathogenesis of RA has greatly improved RA management, some needs are still unmet. About 30% of patients with RA show inadequate response to the first biologic therapy,4–8 which is usually a tumour necrosis factor (TNF) blocker, currently considered with methotrexate (MTX) as the ‘gold standard’ in RA therapy.1 After failure of at least one TNF inhibitor, the response rate of biological agents is 20–40% after adjustment for the placebo response.9 In addition, the response may decrease over time in some patients. Finally, only a few patients achieve remission or low disease activity, the rate being lower for established than early RA.2

Since the remarkable but partial success of TNF inhibitors, tremendous efforts have been made to offer additional treatment options for RA patients. Thus, several biologics drugs with other modes of action have been developed, which block cytokines other than TNF or cells involved in the pathogenesis of RA.10 This has led to the licensing of biological DMARDs inhibiting interleukin 1 (IL-1) (anakinra), IL-6 receptor (tocilizumab), B cells (rituximab) and T-cell costimulation (abatacept).1 ,3 The availability of this variety of biological drugs has offered additional strategies for rheumatologists in daily practice, but refractory patients remain, and many still have active disease and progressive disability. Another ‘fashionable’ and more recent strategy has been to try to identify biomarkers that could identify subpopulations of patients with better response to a specific drug.11 However, biomarkers, so far, have failed to predict the clinical response to any biological or synthetic DMARD at …