Reviews & Analysis

In this Review, Thomas Aigner and colleagues discuss the pivotal role of chondrocytes in osteoarthritis. The article focuses on changes in the anabolic, catabolic, phenotypic and proliferative behavior of chondrocytes that affect the maintenance of the extracellular matrix, the primary target of osteoarthritic cartilage degradation.

The effects of biologic agents on the liver are both a cause for concern with regards to potential toxicity and an opportunity to discover new therapeutic opportunities, as is discussed in this Viewpoint.

Thalidomide was widely disparaged following recognition of its teratogenicity; however, its immunomodulatory activities have become increasingly apparent. At present, thalidomide is approved by the FDA only for use in the treatment of multiple myeloma and erythema nodosum leprosum. In this Viewpoint, Dr Lehman discusses reports in the literature which indicate that thalidomide is effective for a wide variety of immune-mediated conditions.

The main emphasis of research in osteoarthritis has been the delineation of the mechanism of articular cartilage degradation. In this Viewpoint, Dr Bailey and colleagues discuss the importance of bone in osteoarthritis, the focus of which has been neglected to date.

Our improved understanding of the intercellular and intracellular pathways involved in the pathophysiology of rheumatoid arthritis has enabled novel targets for biologic agents to be identified. The most promising of these targets, which include cytokines, adipokines and microparticles, are discussed in this Review.

A complex interplay of factors is thought to lead to adult-onset Still's disease, a rare systemic inflammatory disease. As discussed in this article, increased levels of several proinflammatory cytokines are thought to be important in the pathogenesis of this disease, and targeted treatments, such as biologic agents, are likely to increase in popularity.

Clinical and radiographic changes are currently used to diagnose osteoarthritis, but these changes occur late in the course of disease, and show poor sensitivity for monitoring progression. The use of biological markers of joint metabolism might improve prediction of disease progression, as outlined in this Review.

Glucosamine is indicated for the treatment of osteoarthritis, but questions surround its efficacy and long-term safety. In this article, Professor Wollheim discusses the results of recent trials, and provides his opinion on when glucosamine could be used.

The synovium is the primary target of disease in various forms of arthritis. In this Viewpoint, the authors discuss the possibilities of making a diagnosis based on clinical examination, routine laboratory tests, radiographic examination of the synovium, or by synovial fluid analysis or biopsy.

The proper interpretation of the results of clinical trials is essential and is influenced by four key elements of the trial design: the primary endpoint, the test statistic, the target treatment effect and the study power. These four factors, and their impact on interpreting the results of clinical trials, are outlined in this article.

Use of contraceptives by women with rheumatic diseases, especially those with systemic lupus erythematosus, has long been thought to carry risks. This Review describes current contraceptive options, their general risks and benefits, and specific safety issues relevant to patients with rheumatic diseases.

Immunoglobulin-based therapies, including monoclonal antibodies and intravenous immunoglobulin, are effective therapeutic approaches for patients with rheumatic diseases who do not respond to conventional anti-inflammatory drugs. Several such therapies have been approved for clinical use; the mechanisms of action of these therapies are discussed in this Review.

Polymyositis and dermatomyositis are two subsets of myositis, also known as idiopathic inflammatory myopathies. Characterized by weakness, decreased endurance and increased inflammation of muscles, the disease onset and progression of these myopathies varies from patient to patient, as do the histopathologic characteristics, so advances in diagnostic and outcome tools are invaluable for clinical research and clinical practice.

There has been much speculation on the potential use of kinase inhibitors, such as imatinib mesylate, for the treatment of autoimmune rheumatic diseases. Imatinib inhibits a select set of tyrosine kinases at submicromolar concentrations. In this Viewpoint, the authors discuss how imatinib could provide a potent therapeutic option for a variety of autoimmune and inflammatory diseases, for which current therapies are insufficient.

Physician–investigators carrying out clinical research have moral, ethical and legal responsibilities. A variety of official documentation must be in place before a trial commences, and good clinical practice must be followed throughout. A suitable infrastructure, in terms of equipment, staff and space, is also required. These issues are outlined in this article.

Etanercept, adalimumab and infliximab all specifically antagonize tumor necrosis factor (TNF), but with differential clinical efficacy. Differences in their pharmacology and mechanisms of action, and disease heterogeneity, might account for this therapeutic disparity, as might reverse signaling by transmembrane TNF in response to anti-TNF antibodies, all of which are reviewed here.

Scleritis, a chronic inflammation that involves the outermost coat and skeleton of the eye, often occurs in patients with immune-mediated systemic inflammatory conditions, such as rheumatoid arthritis. In this Review, the authors discuss the clinical presentation, etiology, pathogenesis and treatment of this often extremely painful condition.