The Giants (biologicals) against the Pigmies (small molecules), pros and cons of two different approaches to the disease modifying treatment in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that, if untreated, can lead to disability and reduce the life expectancy of affected patients. Over the last two decades the improvement of knowledge of the pathogenetic mechanisms leading to the development of the disease has profoundly changed the treatment strategies of RA through the development of biotechnological drugs (bDMARDs) directed towards specific pro-inflammatory targets involved in the RA network. To date, the therapeutic armamentarium for RA includes ten bDMARDs able to produce the depletion B-cells, the blockade of three different pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-6 and interleukin-1), or the inhibition of T-cell co-stimulation. The introduction of these new compounds has dramatically improved outcomes in the short and long term, although still a significant proportion of patients are unable to reach or maintain the treatment target over time. The identification of the fundamental role of Janus kinases in the process of transduction of the inflammatory signal within the immune cells has recently provided the opportunity to use the new pharmacological class of small molecules for the therapy of RA, further increasing the number of treatment options. In this review the PROS and CONS of these two drug classes will be discussed, trying to provide the evidence currently available to make the right choice based on the analysis of the efficacy and safety profile of the different drugs on the market and close to marketing.