JAK Inhibitors: What Is New?

Three Janus kinase (JAK) inhibitors are approved for rheumatoid arthritis (RA) with a fourth awaiting approval. Multiple clinical trial results with these molecules have recently been reported. These were the first small molecule oral targeted synthetic DMARDs (tsDMARDs) to be approved for RA.

Preclinical studies have suggested differential affinity for JAK isoform inhibition but it is not presently clear that there is any difference in efficacy in the clinic with these therapies. Preliminary data has suggested that filgotinib may have a modestly different safety profile but lacking direct comparisons, this will be difficult to confirm. Long-term safety studies have suggested similar safety signals to biologics although a possible signal for VTE/PE risk has been noted with tofacitinib and baricitinib. Having an oral small molecule such as the JAK inhibitors with similar or better efficacy than biologics has been a major advance in RA treatment.