Reviews & Analysis

Novel therapies to reduce the progressive and destructive nature of inflammatory joint disease are always welcome, provided that safety is not compromised. Among the many 2015 studies in the field, we highlight a targetable mechanism of uric-acid-induced inflammation in gouty arthritis and the expected efficacy — but unforeseen safety concerns — of anti-IL-17 antibodies.

Key advances in lupus research in 2015 highlight the contribution of T cells to the pathogenesis of the disease. The findings not only shed light on the regulation and activity of these cells, but also suggest several novel therapeutic targets.

Since glucocorticoids were first used to treat patients with rheumatoid arthritis in 1949, they have become the most common therapy for inflammatory disorders; however, their use is associated with major metabolic adverse events. Here, we review three 2015 reports with clinical and fundamental implications for the use of glucocorticoid therapy in rheumatology.

The treatment and study of systemic sclerosis (SSc) is entering a new era with the reporting and preparation of several randomized controlled trials according to an improved understanding of SSc pathogenesis. Advances in trial designs reported in 2014 should now be built upon with further improvements to patient selection to enable targeting of therapies to specific subgroups of patients with SSc.

Optimizing the management of childhood arthritis requires detailed knowledge of the disease in an individual patient. Advances in 2014 show how in-depth genetic studies and insights into immunopathogenesis could translate into clinical biomarkers and, eventually, individualized therapy.

Even though activation of immunity is associated with bone destruction, new mechanisms have been described in 2014 through which immunology-associated pathways can cooperate to support osteogenesis. These advances support the view of the immune system as a central mechanism which can regulate bone homeostasis, regeneration and destruction.

2014 saw the emergence of a novel rheumatoid arthritis therapy to rival methotrexate, as well as advances in our understanding of mouse T-cell biology and of the cross-talk between the nervous system and the immune system. How will these advances affect the future of rheumatoid arthritis research and therapy?

Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described for the first time in 2014. As well as providing insights into the molecular basis of several rare immunological disorders, the discoveries have implications for their diagnosis and treatment.

Important advances in 2014 foster new perspectives on definitions of early and end-stage disease, and promote a shift in the clinical management of osteoarthritis (OA) through implementing treatment algorithms intended to minimize strain on current health-care models. Collectively, these changes shed new light on developing and optimizing approaches to OA treatment.

Several advances in 2013 have improved our understanding of how epigenetic mechanisms affect autoimmune disorders. Many new insights were made into the regulation of gene expression by DNA methylation in systemic lupus erythematosus. For rheumatoid arthritis, complex interrelationships between DNA methylation and microRNAs in regulating gene expression were described.

With every passing year, research on the pathogenesis of rheumatoid arthritis benefits from discoveries in other scientific fields. Three of the best examples that illustrate the benefit of such interdisciplinary bridges and the effects they have on our understanding of rheumatoid arthritis are presented here.

2013 has witnessed the maturation of imaging science with rheumatology research, in part due to large, public databases. Using imaging in osteoarthritis (OA) as an example, breakthroughs include further elucidation of the relationship between obesity and OA, and identification of the importance of bone and meniscus shape in OA development.

Clinical, basic and translational research in systemic lupus erythematosus are fast-moving fields. 2013 has seen the publication of some potentially landmark papers, which not only explore the potential of novel agents but also glean new insights from past trials.

In 2013, much progress has occurred in gout research. Imaging continues to help elucidate aspects of pathophysiology and now suggests that healing of erosions could occur when urate levels are reduced dramatically. New genetic loci associated with hyperuricaemia have been identified and management strategies for prophylaxis of gout flares continue to evolve.

A number of microRNAs have been implicated in the pathogenesis of various rheumatic diseases, and evidence in support of the therapeutic potential of microRNA-based strategies for these conditions is growing, as demonstrated by several new findings published in 2012.

Tissue engineering and regenerative medicine have advanced rapidly towards the development of therapeutic solutions for musculoskeletal disorders. In 2012, breakthroughs have been made in the guidance of adult stem cell homing, the tissue regenerative activity of stem-cell-derived extracellular matrix has been tested, and novel, mechanically superior biomaterials have been fabricated.

Developments in our knowledge of the aetiology and pathogenesis of rheumatoid arthritis continued apace in 2012, and several important new advances were reported in the therapy of this disease. Culminating in the approval of a new therapy in the USA, the year offered new insights for clinicians and fresh hope for patients.

In 2012, several new concepts emerged that widen our view of the regulation of bone mass in health and disease. Three key studies outline these discoveries, which affect our understanding of the skeletal system, particularly its physiological function and the changes it undergoes during inflammatory disease.

2012 has witnessed new developments in targeted therapies for osteoarthritis, and in ways to identify those patients who might benefit most from their application. Together, these advances could go some way to addressing the urgent need for disease-modifying treatments for this common disease.

Advances in 2012 have helped to solve several established mysteries in spondyloarthritis (SpA)—why T-cell-directed therapies have not delivered the expected efficacy and how the IL-23–IL-17 cytokine axis is linked to the specific pathology of SpA. The opportunity to influence disease progression at inflammatory lesions using anti-TNF agents may be fleeting.