Reviews & Analysis

Emerging science characterizes lupus as a systemic spectrum disorder, rather than as multiple single-organ diseases. So is it time to capitalize on this progress and begin evaluating treatment options on the basis of physiologic mechanisms instead of organ involvement?

Compliance with reporting clinical trial results varies across research fields and types of sponsors. In rheumatology, most industry-funded trials of biologic agents are currently reported promptly. Optimizing clinical research will nevertheless require steps beyond deposition of summary results, including making raw data and protocols available, and assuring independence of the research agenda.

In a phase II–III trial, a novel antibody targeting IL-6 receptor α (IL-6Rα), sarilumab, conferred clinical, functional and structural benefits in rheumatoid arthritis. These results, though, seem quite similar to those for tocilizumab, the existing anti-IL-6Rα antibody, as well as for other agents currently in development that target this same pathway.

As patents expire for biologic reference products (innovators), biosimilar agents are joining the treatment landscape in rheumatology. Release of an ACR position statement on biosimilars prompts US rheumatologists to focus on issues relating to the clinical use of these agents and can also be helpful for rheumatologists in other regions where biosimilar agent regulatory processes are not yet fully implemented.

Considerable progress has been made in understanding the pathologic processes and pathophysiology of Kawasaki disease. This article also discusses genetic susceptibility to Kawasaki disease and describes current approaches to treatment of the acute stage of the disease.

Fibromyalgia symptoms include nonrestorative sleep and fatigue, and patients with fibromyalgia have showed reduced short-wave sleep and abnormal α-rhythms, which are suggestive of poor-quality sleep. Conversely, sleep deprivation in healthy individuals can cause symptoms of fibromyalgia and is a risk factor for developing chronic widespread pain. In this Review, Choy describes pain pathways that have been associated with sleep deprivation, and explores the hypothesis that sleep dysfunction is a pathogenic stimulus of fibromyalgia.

New technologies to identify loci associated with diseases are enabling classification of diseases according to genetic 'architectures'. In this Review, the authors show that patients with seronegative and seropositive rheumatic diseases have distinct genetic signatures, enabling an alternative classification to serology and providing hope for personalizing medicine.

This article reviews what is known about the role of the IL 23–IL 17 immune pathway at different stages in the development and progression of chronic immune-mediated inflammatory diseases, in particular rheumatoid arthritis and spondyloarthritis. The author draws on findings from disease-specific animal models and humanex vivostudies as well as data from clinical trials of therapies targeting the IL 23–IL 17 axis.

Is the risk of hospitalization and death due to serious infections on the rise in patients with systemic lupus erythematosus (SLE)? A population-based study provides insights into these trends and highlights the need for safe, effective treatment strategies in SLE.

Treatment optimization studies have paved the way for success of new therapies in paediatric oncology. The majority of children with cancer are treated within treatment optimization study protocols (TOSPs), but this is not the case for children with common rheumatic diseases such as juvenile idiopathic arthritis. In this Opinion article, Niehues suggests the recruitment of children with rheumatic diseases into TOSPs, making use of rheumatology research networks already established, would secure standardized treatments and outcome measures and could improve patient care considerably.

This article discusses the many heritable and nonheritable factors contributing to primary osteoporosis, focusing on osteogenesis imperfecta, juvenile osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of osteoporosis, but could also lead to the discovery of new therapeutic targets.

The most common form of eye inflammation associated with juvenile idiopathic arthritis (JIA) is chronic anterior uveitis, which, if inadequately treated, can lead to ocular complications, including blindness. Sen and colleagues discuss the epidemiology, immunopathogenesis and management of JIA-associated uveitis, and describe the potential for biomarkers to improve its treatment.

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.

Observational studies are increasingly used to evaluate the safety and effectiveness of drugs for rheumatoid arthritis, but these studies are limited by inherent biases, including confounding by indication. This Perspectives article describes how these methodological limitations could be overcome by using the active-comparator design and the new-user design.

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.

Anti-citrullinated protein antibodies are a distinctive feature of a subset of patients with rheumatoid arthritis (RA). A new report investigates how lung inflammation in patients with chronic obstructive pulmonary disease affects protein citrullination, providing an additional piece of information on the potential link between airway inflammation and RA.

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.