Reviews & Analysis

The next challenge in rheumatoid arthritis (RA) therapy is the maintenance of disease remission with a minimal-treatment regimen. In this Review the authors propose that this goal could be achieved by restoring a state of immune tolerance and discuss antigen-independent and antigen-specific approaches for the induction of tolerance in the treatment of RA.

The establishment of new benchmarks for treatment outcomes promises to drive great advances in rheumatoid arthritis therapy, but data on 'real life' experience with biologic therapy demonstrate that geographic location influences the stage of disease at which these agents are initiated.

Seemingly contrasting genetic backgrounds in anti-citrullinated-protein antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) support the notion that these are in fact two distinct disease subsets, with different underlying pathogenesis, that might need tailored treatment strategies.

Autoimmune-like syndromes (AILS), such as lupus-like syndrome and inflammatory neuropathies, are occasionally seen in patients treated with tumor necrosis factor (TNF) antagonists, although the pathogenetic mechanisms underlying these syndromes are not well understood. In this article, the author suggests that infections might trigger, amplify or mimic AILS in patients receiving anti-TNF therapy.

OA is not a disease in short supply of phenotypic definitions. Indeed, numerous classification options complicate the design of genetic studies seeking associations within the obscuring array of heterogeneity. New recommendations offer some progress toward clarifying OA definitions, but much-needed guidelines are wanting.

In this Review, the authors describe the marked differences in clinical presentation, prognosis, disease assessment and treatment options that exist between pediatric and adult-onset systemic lupus erythematosus, which highlight our need to find new ways of improving disease control in affected children.

The use of genetically modified animal models has helped to identify the crucial factors involved in the differentiation and function of osteoclasts. This Review discusses the main observations in osteoclast biology derived from animal models, and outlines the osteoclast-targeted therapies that have developed from these studies.

Despite greatly advancing the therapy of rheumatoid arthritis, the clinical use of biologic agents leaves unanswered a number of important questions. As discussed in this Review, ongoing efforts to improve our understanding of these issues should aim to establish the optimum use of biologic therapy, with the ultimate goal of achieving the best possible therapeutic outcomes in an individual patient.

The potential of epigenetics to explain the complex links between environmental triggers and genetic susceptibility is captivating researchers in many diseases. As this article describes, considerable evidence suggests that aberrant epigenetic modifications contribute to pathogenesis of these diseases, and drugs that can reverse such changes are a tantalizing prospect for future therapy.

A substantial proportion of patients with rheumatoid arthritis do not respond to tumor necrosis factor blocking therapy. Results of a large genome-wide association study demonstrate evidence of novel genetic factors that determine response to treatment, which could provide a basis for individualizing therapy.

In patients with active rheumatoid arthritis despite therapy with DMARDs, treatment with a spleen tyrosine kinase inhibitor has achieved similar response rates to those achieved in clinical trials of other drugs, including biologic agents. Where might these agents fit in the current armamentarium against this disease?

Several new recommendations for the vaccination of adults with autoimmune inflammatory diseases could represent an important step forward in the prevention of infections in these high-risk patients.

In 2010, important research into the systemic autoinflammatory diseases has confirmed and extended the role of IL-1 inhibition in hereditary autoinflammatory disorders, demonstrated a novel treatment for a dangerous complication, and expanded the spectrum of systemic autoinflammatory diseases while further implicating autoinflammation in the complications of the metabolic syndrome.

Important advances have been made in gout therapeutics in 2010. In addition to the development of novel biologic agents, progress has been made in the safe prescribing of colchicine. However, colchicine also became the subject of considerable controversy in the USA when one brand of this drug was granted exclusivity.

Novel findings shed light on the role of tumor necrosis factor in ankylosis and inflammation, pointing to new indications for blockade of this cytokine in treating spondyloarthritis. At the same time, the identification of other potential targets for therapy could expand the treatment options for this family of inflammatory disorders.

From evidence pointing to a possible etiologic role for microbes to the development of new strategies and agents to treat early and established disease, 2010 has seen the publication of several interesting findings in the field of rheumatoid arthritis.

How can we optimize the management of osteoarthritis? Recent studies into the efficacy and mechanisms of interventions that target nociceptive mechanisms, lower-extremity musculature and ligament integrity reflect the progress being made in this field.

In several areas of investigation, the results of a bumper year in osteoporosis research are set to stoke rather than settle debate. From the origins of bone health to the use of established and experimental therapies, the new findings will be discussed into 2011 and beyond.

The adduction moment generated during walking is associated with the development and progression of knee osteoarthritis. Nonsurgical biomechanical approaches aim to reduce the knee adduction moment. In this Review the authors discuss various such strategies, including footwear interventions and gait modification approaches as well as the use of valgus knee braces.

The disparity in the occurrence of rheumatoid arthritis (RA) between men and women is well documented, but the reasons for this difference remain poorly understood. In this article, the authors discuss the factors that might explain the sexual dimorphism of RA, including genetic, endocrine and behavioral differences, and how improving our understanding of the influence of these factors might lead to the development of novel treatments for patients with this disease.