ReviewKinase inhibitors: A new tool for the treatment of rheumatoid arthritis

- Kinases are rationale therapeutic targets given their downstream signaling effects.
- The Jak inhibitor tofacitinib was recently approved for RA.
- Syk inhibition with fostamatinib shows promise in clinical studies.
- Targeting PI3Ks, Btk and upstream of p38 MAPK represent future advances.
- Abrogation of homeostatic pathways compromises benefits of some kinase inhibitors.

Despite aggressive immunosuppression with biologics and traditional DMARDs, achieving disease remission remains an unmet goal for most rheumatoid arthritis (RA) patients. In this context, there is a demand for novel treatment strategies, with kinase inhibitors expected to enrich the existing therapeutic armamentarium. In RA some kinases participate in the generation of pathogenic signaling cascades. Pharmacologic inhibition of kinases that mediate pathogenic signal transduction heralds a new era for RA therapeutics. Oral inhibitors of JAKs, Syk, PI3Ks, MAPKs and Btk are under development or in clinical trials in patients with RA. In this review, we discuss the scientific rationale for the use of kinase inhibitors in RA and summarize the experience from clinical trials.