Journal Article

Pathogenetic insights from the treatment of rheumatoid arthritis

Schett, Georg, McInnes, Iain B

2017

Overview

Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage, functional loss, and comorbidity. The development of effective biologics and small-molecule kinase inhibitors in the past two decades has substantially improved clinical outcomes. Just as understanding of pathogenesis has led in large part to the development of drugs, so have mode-of-action studies of these specific immune-targeted agents revealed which immune pathways drive articular inflammation and related comorbidities. Cytokine inhibitors have definitively proven a critical role for tumour necrosis factor α and interleukin 6 in disease pathogenesis and possibly also for granulocyte–macrophage colony-stimulating factor. More recently, clinical trials with Janus kinase (JAK) inhibitors have shown that cytokine receptors that signal through the JAK/STAT signalling pathway are important for disease, informing the pathogenetic function of additional cytokines (such as the interferons). Finally, successful use of costimulatory blockade and B-cell depletion in the clinic has revealed that the adaptive immune response and the downstream events initiated by these cells participate directly in synovial inflammation. Taken together, it becomes apparent that understanding the effects of specific immune interventions can elucidate definitive molecular or cellular nodes that are essential to maintain complex inflammatory networks that subserve diseases like rheumatoid arthritis.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adaptive immunity / Arthritis / Arthritis, Rheumatoid - drug therapy / Arthritis, Rheumatoid - immunology / Arthritis, Rheumatoid - pathology / Arthritis, Rheumatoid - physiopathology / Autoimmune diseases / Biological effects / Cellular communication / Clinical trials / Colony-stimulating factor / Cytokine receptors / Cytokines / Damage / Depletion / Drug development / Drug therapy / Drugs / Functional anatomy / Granulocyte-macrophage colony-stimulating factor / Humans / Immune response / Immune system / Immunosuppressive agents / Immunotherapy - methods / Inhibitor drugs / Inhibitors / Interferon / Interleukin 6 / Internal Medicine / Janus kinase / Janus Kinases - antagonists & inhibitors / Janus Kinases - metabolism / Lymphocytes B / Macrophages / Medical research / Pathogenesis / Receptors / Rheumatoid arthritis / Signal Transduction / Signaling / Tumor necrosis factor / Tumors