Review Articles in 2015

Cardiovascular disease and rheumatoid arthritis (RA) share genetic and environmental risk factors, as well as pathological processes. This article outlines the mechanisms that might contribute to the prevalence and characteristic phenotype of atherosclerosis in RA, with an emphasis on inflammation.

Circadian rhythms are well established as having an important role in human biology. In this Review, circadian biology is presented in reference to the regulation of rheumatoid arthritis and the potential for chronotherapeutic intervention.

Autoimmune congenital heart block is more likely to occur in the babies of women with rheumatic diseases, particularly women seropositive for anti-Ro or anti-La autoantibodies. Here, the authors provide advice for the management of these women and their babies in juxtaposition to a systematic assessment of the epidemiology and classification of the disease.

Several molecular pathways and cellular effector functions have been described for the pathology of rheumatoid arthritis, but fundamental questions remain about the basic organization of disease-driving immune responses. In this Review, Benson and colleagues describe how intact tissue imagingin vivohas facilitated studies of the dynamic nature of cellular immune responses, and how these findings can be translated to new therapeutics.

In the field of musculoskeletal tissue replacement, scaffold-based tissue engineering is evolving rapidly, in preclinical studies as well as clinical applications. In this article, the authors discuss the core concepts of this approach and provide an overview of the use of scaffolds in engineering various musculoskeletal tissue types.

Gene therapy can produce nascent therapeutic proteins in specific sitesin vivo, a powerful tool that could revolutionize treatment for many diseases. However, this potential has not yet been translated into restoration of the musculoskeletal system in patients with rheumatic diseases. Here, the technology, barriers to translation, and clinical trials are reviewed.

Despite the successes of biologic therapies in rheumatoid arthritis (RA), not all patients respond to available drugs, and systemic toxicity of some drugs often lead to therapy discontinuation. New developments in polymer–drug conjugates and nanoparticle technology can improve drug efficacy in patients with RA by targeting therapeutic agents to inflamed tissues and extending the half-life of drugs. In this Review, Ferrari and colleagues describe new techniques being explored to improve accumulation of therapeutic agents in the inflamed synovium—a new strategy to boost drug efficacy at disease sites without affecting healthy tissues.

Tendon disorders are common and are a major cause of musculoskeletal pain, but the development of effective therapies requires detailed knowledge of the biology of this mechanosensitive musculoskeletal tissue. As well as providing an overview of tendon physiology and pathology, this article reviews the mechanical and biological factors that contribute to tendon development, homeostasis and repair, drawing on evidence from experimental models and developmental biology.

After outlining the rationale for injecting viable cells into the degenerating intervertebral disc (IVD), Sakai and Andersson provide an overview of basic and preclinical studies as well as ongoing clinical trials of cell therapies for IVD degeneration. Consideration is also given to various barriers to the development of these therapies and possible solutions to overcome such obstacles.

Targeted therapies and novel strategies to optimize their use enable many patients with RA to achieve a state of low disease activity or even remission, which can be maintained even after tapering or withdrawal of biologic DMARDs. In this article, Smolen and Aletaha review current concepts of RA treatment and the clinical evidence for their effectiveness, in the context of relevant issues such as factors influencing response to therapy, the 'window of opportunity' hypothesis and definitions of treatment targets.

The treatment of juvenile idiopathic arthritis (JIA) has improved markedly in past years, but sustained remission off-medication is still rare. In this Review, Hinze et al. discuss existing treatment approaches and guidelines, with a focus on targeted and patient-centred therapies developed to optimize management strategies for patients with JIA.