State-of-the-art: rheumatoid arthritis

Abstract

The understanding of the pathogenesis and optimal therapeutics for rheumatoid arthritis (RA) has advanced remarkably over the last decade. This review highlights these key advances, particularly the outcomes of genome-wide scans which have provided an increasingly robust appraisal of the complex genetics that underpin RA. Such observations are placed in pathogenetic context, particularly concerning the breach of tolerance that presages synovitis and the mechanisms that subserve chronicity. The key therapeutic strategies and treatment agents, both conventional and biological, now available to effectively manage the disease are described. Throughout the review, emphasis is placed on unanswered questions and challenges in this exciting field.

Consenso da Sociedade Brasileira de Reumatologia 2011 para o diagnóstico e avaliação inicial da artrite reumatoide

“…However, although useful for characterizing patients with worse prognosis, the high costs of HLA-DRB1 typifying still limit its use in daily practice. 59,60 …”

Pharmacokinetics, Safety, and Tolerability of GLPG0259, a Mitogen-Activated Protein Kinase-Activated Protein Kinase 5 (MAPKAPK5) Inhibitor, Given as Single and Multiple Doses to Healthy Male Subjects

“…A considerable advance in the effective treatment of RA came from the introduction of the biologic therapeutics that neutralize cytokines or their receptors (TNFa and interleukin [IL]-6) or that inhibit cellular activation (B-cell or T-cell activation). [4,5] However, because of the high production costs, inconvenience of parenteral administration, increased risk of infections, and potential immunogenicity of biologics, there is still a need for less expensive and orally administered drugs. [4] Hence, the development of small-molecule inhibitors targeting disease-relevant signal transduction pathways is being pursued by various companies.…”

Rheumatoid Arthritis: Prospects for Stopping the Runaway Train by Reintroduction of Tolerance

“…Twenty five years ago the consequences were devastating, with patients routinely suffering long term damage, loss of function, and increased mortality [2]. Since then the addition of disease modifying rheumatic drugs (DMARDs) and more recently biologic medications such as anti-tumor necrosis factor α (TNFα) to our treatment arsenal has dramatically improved long term outcomes [3,4]. However, these strategies all target downstream consequences of the disease in an attempt to suppress one or more aspects of an over active immune system (Figure 1).…”