New drugs beyond biologics in rheumatoid arthritis: the kinase inhibitors

• Published in: Rheumatology (Oxford, England) Vol. 50; no. 9; pp. 1542 - 1550
• Main Authors: BONILLA-HERNAN, M. Gema, MIRANDA-CARUS, M. Eugenia, MARTIN-MOLA, Emilio
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2011
• Subjects: Animals; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Biological and medical sciences; Cytokines - metabolism; Diseases of the osteoarticular system; Humans; Inflammatory joint diseases; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Janus Kinases - antagonists & inhibitors; Medical sciences; Mitogen-Activated Protein Kinase 14 - antagonists & inhibitors; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Syk Kinase; Immunopathology; fostamatinib; Enzyme; Transferases; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Signalling; tofacitinib; Chronic; Treatment; kinases; Kinase; Rheumatoid arthritis; Small molecule
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ker192

Orally available small molecule compounds have recently been developed for the treatment of RA, and inhibitors of signalling cascades, specifically inhibitors of kinases, have reached advanced stages of clinical development. The p38 mitogen-activated protein kinase blockers have shown poor clinical response despite encouraging preclinical data. In contrast, inhibitors of the non-receptor tyrosine kinases, spleen tyrosine kinase and janus kinase 3, have demonstrated a significant clinical efficacy together with an acceptable safety profile. We herein present a review on published preclinical and clinical data on these new drugs.