Review Articles in 2007

A suitable infrastructure and adherence to regulatory requirements are required to establish a successful clinical trial unit. Once in place, studies must be acquired, contracts negotiated and patients recruited before the clinical investigation can begin. These aspects, which, if successfully carried out, will improve the chances of obtaining future studies, are discussed in this article.

The changing prevalence of the risk factors for gout, which include genetic factors, excess alcohol consumption, purine-rich diet, the metabolic syndrome, diuretic use, and osteoarthritis, are influencing the prevalence and clinical presentation of this common crystal deposition disorder. In addition, as is discussed in this Review, suboptimum management is contributing to the rise in the prevalence of clinically significant symptomatic chronic gout.

Numerous antiangiogenesis drugs have been developed for the treatment of patients with malignancies. These agents, which include vascular-endothelial-growth-factor inhibitors, microtubule disrupters and fumagillin analogues, might also represent new therapeutic options for patients with proliferative synovitis, as is discussed in this Review.

The knee is generally seen as the easiest joint to inject or aspirate; however, a 'dry tap' can occur, when fluid seems to be present but the initial attempt to aspirate it fails. This Primer Review outlines why such difficulties occur when performing arthrocentesis of the knee and suggests ways in which an operator might adjust their technique to deal with this situation.

A widely used alternative to biologic therapy for treating rheumatoid arthritis is treatment using disease-modifying antirheumatic drugs (DMARDs). Methotrexate and sulfasalazine are the most commonly prescribed DMARDs, each of which can be used on its own, or in combination with other DMARDs, in a step-up, step-down, or parallel approach, as is outlined in this Review.

Damage-associated molecular pattern molecules, such as heat shock proteins and S100 proteins, represent tissue danger signals, which mediate inflammatory responses after being released from activated or necrotic cells. These danger signals, and their receptors, could be targets for novel approaches in the treatment of rheumatic diseases, as discussed in this article.

Subgroup analyses are often included in clinical trial papers, but there are numerous pitfalls associated with this approach. Specific guidelines as to how to perform and interpret subgroup analyses should be followed to ensure that appropriate conclusions are drawn and correct clinical decisions are made.

Most pregnant women with rheumatoid arthritis suffer a disease flare within 3 months of delivery of their baby. At present, due to the lack of data on the effects of antirheumatic drugs on the infant, patients feel they have to choose between postpartum disease control and lactation. These issues, and the need for further studies in this area, are highlighted in this Review.

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.

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.

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.

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.

No detailed guidelines exist for treating pain in children with rheumatic diseases. In this Review, the authors discuss the multifactorial nature of pain in these children and advise that pain treatment should be interdisciplinary and consist of nonpharmacologic as well as pharmacologic interventions.