REVIEW Kinase inhibitors: A new tool for the treatment of rheumatoid arthritis Soumya D. Chakravarty a , b , Poulikos I. Poulikakos c , d , Lionel B. Ivashkiv a , b , e , Jane E. Salmon f , George D. Kalliolias a , b , g , ⁎ a Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA b Department of Medicine, Hospital for Special Surgery, New York, NY 10021, USA c Department of Oncological Sciences, The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA d Department of Dermatology, The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA e Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA f Division of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY 10021, USA g Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA Received 7 January 2013; accepted with revision 1 April 2013 Available online 17 April 2013 KEYWORDS Kinase inhibitors; Rheumatoid arthritis Abstract 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. © 2013 Elsevier Inc. All rights reserved. Contents 1. Introduction .......................................................... 67 2. History and pharmacology of kinase inhibitors ....................................... 67 ⁎ Corresponding author at: Hospital for Special Surgery, Research Building 4th floor, 535E 70th Street, New York, NY 10021, USA. Fax: + 1 212 774 2560. E-mail address: kallioliasg@hss.edu (G.D. Kalliolias). 1521-6616/$ - see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clim.2013.04.007 available at www.sciencedirect.com Clinical Immunology www.elsevier.com/locate/yclim Clinical Immunology (2013) 148, 66–78