Volume 9 Issue 3, March 2013

The treat-to-target approach has been a major breakthrough in the treatment of rheumatoid arthritis. Although this strategy has been evaluated in many clinical studies, whether a high level of adherence is feasible in real-world clinical practice remains uncertain.

Evolving understanding of the role of helminths in the pathogenesis of autoimmunity has led to the development of novel therapeutic interventions that are showing promise in patients with immune-mediated diseases. Meanwhile, studies in animal models of arthritis suggest that these new products might also be applicable in autoimmune rheumatic disease.

A rational approach to the management of rheumatoid arthritis (RA) begins with understanding the disease, development of which can be influenced by environmental, genetic and epigenetic factors. Genetic and epigenetic data in RA are revealing insights into pathogenesis and revitalizing the shared epitope hypothesis. These advances are discussed in this Review, alongside approaches to integrating the findings of genetic and functional studies.

Undoubtedly, biologic agents have altered the landscape of therapeutic options for patients with rheumatoid arthritis (RA). Nevertheless, the choice can be bewildering, especially as several different molecules and pathways are the targets of approved and developmental therapies in RA. The authors of this Review provide a guide to navigate the current options and to understand how the picture is likely to evolve in the near future.

The presence of anti-drug antibodies (ADA) can result in the loss of response to anti-TNF biologic agents in patients with rheumatoid arthritis. In this article, van Schouwenburg et al. outline the limitations of current assays for ADA detection and discuss how studying the immune responses caused by the different anti-TNF biologic agents could lead to strategies to help reduce or prevent the development of ADA.

Advances in our understanding of immune cell receptors and the development of biologic agents targeting them have revolutionized the treatment of rheumatoid arthritis (RA). Now, inhibitors of kinases integral to the signalling pathways downstream of these receptors have been added to the therapeutic armamentarium. This Review discusses the signalling pathways and small-molecule inhibitors of their component kinases that have already shown, or are predicted to show, promise in the treatment of RA.

Drug development, underpinned by randomized controlled trials, has greatly advanced the the treatment of rheumatoid arthritis (RA). However, modern principles and goals of RA management raise new challenges and call into question the appropriateness of traditional trial designs. This Review discusses these designs and the associated challenges, and outlines opportunities that arise from innovative trial designs.

Late twentieth century progress in DMARD therapy for rheumatoid arthritis (RA) has been complemented in this millennium by the advent of targeted biologic therapy and novel small-molecule drugs. Amid this seeming progress, however, results for individual patients are often disappointing. These five specially commissioned Reviews and one News & Views article, written by key opinion leaders in research and clinical practice, summarize emerging insights into the underlying basis of RA, how best to use existing therapies, new treatment targets and progress in targeting them, and how to gain maximum benefit from the opportunities afforded by clinical trials of new agents.