Kinase inhibitors: the next generation of therapies in the treatment of rheumatoid arthritis.
Rheumatoid arthritis (RA) can be the source of significant pain and functional limitation. The past 20 years have seen a transition in treatment goals away from mere pain management toward disease modification through the suppression of autoimmunity. Disease-modifying anti-rheumatic drugs, such as methotrexate and biologic agents, impair disease progression and joint destruction. However, despite these achievements, a substantial subset of RA patients does not respond to or cannot tolerate current treatments for RA. Scientific insight into the cellular pathways of inflammation has revealed new therapeutic targets for the treatment of autoimmune diseases like RA. Attention has focused on pathways mediated by Janus kinase (JAK), mitogen-activated protein kinase (MAPK), and spleen tyrosine kinase (Syk). This review article summarizes the evidence supporting the use of various kinase inhibitors, including the newly approved JAK inhibitor tofacitinib, in the treatment of RA.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Lindsey A
LA
MacFarlane
Derrick J
DJ
Todd
D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D011494:Protein Kinases; D053612:Janus Kinases
kinase inhibitors; rheumatoid arthritis; tofacitinib; treatment