Reviews & Analysis

The effect of biological therapies on cancer risk in JIA is controversial owing to confounding factors such as the use of concomitant immunosuppressants. A study has shed new light on this association, but questions still remain on the effect of the disease itself and biological therapies on cancer risk.

Tissue engineering to repair diseased or injured cartilage could be revolutionized by the development of a novel cell-homing strategy that overcomes several barriers inherent in the use of existing techniques.

The link between glucocorticoid use and bone loss, with increased fracture risk, necessitates care in prescribing these potent anti-inflammatory drugs. What impact will new ACR recommendations—incorporating new clinical trial data and modern methodology for guideline development—have on ensuring that patients receive proper management to reduce the negative impact of glucocorticoids on bone health?

Macrophages have important roles in the induction and resolution of inflammation, but the intracellular pathways from inflammatory signals to pain response remain unclear. A recent study demonstrates that the P2X4 receptor mediates inflammatory pain by inducing formation of the potent lipid mediator prostaglandin E₂.

Genome-wide association studies of human diseases have uncovered large numbers of common genetic variants with small effect sizes; however, rare genetic variants with large effect sizes might have greater relevance with respect to disease heritability. The identification and characterization of rare variants—such as those recently discovered in SIAE—is, therefore, likely to be a major endeavor in the field in the coming years.

Digital ulcers in patients with systemic sclerosis (SSc) can cause considerable disability; however, clinical trials addressing the treatment and prevention of digital ulcers in SSc are rare. A study has evaluated the potential benefit of the endothelin receptor antagonist bosentan in the treatment of SSc-related digital ulcers.

A meta-epidemiological study has revealed that the inclusion of small studies in meta-analyses of osteoarthritis interventions could lead to an overestimation of the benefit of these interventions. Does this mean meta-analyses should be restricted to trials with large sample sizes?

Clinical trials demonstrate that intensive treatment of early rheumatoid arthritis with a combination of DMARDs improves short-term outcomes. An extension study from a pivotal trial has now shown that such intensive early therapy can achieve a reduction in the rate of erosive progression over a period of 11 years.

Therapeutic strategies are in development that aim to use T_REG cells in autoimmune diseases. The feasibility of such an approach is challenged, however, by recent findings suggesting that the chronic phase of autoimmune inflammation might not be controlled by these cells. What impact could this study have on the development of T_REG cell-based therapies for human diseases?

Bacterial infection is known to trigger a number of autoimmune disorders, an observation that indicates a potentially important role for antibiotics in treating these diseases. Indeed, results from an experimental model of autoimmune arthritis in mice suggest that antibiotics can prevent the onset of disease.

Immunosuppression has been associated with viral reactivation in patients with chronic viral infections. A prospective study has concluded that it is safe to use anti-tumor-necrosis-factor agents in patients with chronic hepatitis B virus infection receiving antiviral prophylaxis. Is there sufficient evidence to back up this conclusion?

Strategies to reduce the immunogenicity that occurs following treatment with most biologic agents are a growing subject of investigation. A novel approach to induce tolerance to a therapeutic monoclonal antibody, alemtuzumab, has yielded promising results.

Patients over the age of 50 have an increased risk of mortality following hip fracture, which is dependent on factors such as health and post-fracture comorbidities. Findings from a meta-analysis highlight the need to improve fracture management through systematic approaches that will also reduce mortality.

Although the benefits of exercise for individuals with fibromyalgia are well known, it can be difficult for individuals to begin or maintain an exercise regimen. A recent trial examined whether defining “exercise” as increases in regular home-based physical activities might improve exercise compliance.

A key component of Paget disease of bone is a localized increase in osteoclastic activity, which might be attributable, in part, to mutations in the sequestosome 1 gene. A study has identified three new genes that regulate osteoclasts and are implicated in Paget disease; however, the clinical utility of these findings remains questionable.

Both etanercept and ustekinumab have been shown to be strikingly effective in patients with psoriasis. A phase III trial comparing these two biologic agents for the treatment of moderate-to-severe psoriasis found that ustekinumab was superior to high-dose etanercept over a 12-week period; however, several questions remain to be addressed.

Studies of mouse models of lupus provided the rationale for targeting BAFF in the treatment of patients with systemic lupus erythematosus, and could also help explain why individuals might differ in their response to this therapeutic approach.

Treatment guidelines are an increasingly prominent topic of discussion in medicine. Can rheumatologists avoid the 'fatal flaw' inherent in attempts to standardize treatment decision-making—in which overly strict adherence to guidelines might be pursued at the expense of optimizing individual patients' outcomes?

A systematic review of randomized controlled trials reveals some differences in the effects and indications of the three pharmalogical treatments for fibromyalgia. What can prescribing physicians glean from the results?

Tapering or even discontinuation of drug therapy for rheumatoid arthritis is a desirable goal, given patient preferences in addition to safety and financial concerns, but the implications of this approach are far from clear. A multicenter study conducted in Japan has explored whether stopping treatment with a tumor necrosis factor inhibitor is a viable option once a state of low disease activity has been attained.