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In the PRECISION trial involving patients with arthritis, moderate doses of a selective cyclooxygenase 2 inhibitor were not associated with increased cardiovascular events compared with submaximal doses of nonselective NSAIDs. The balance between pain relief and cardiovascular risk with NSAIDs should be further investigated in patients with chronic inflammatory rheumatic diseases.

Glucocorticoids are the mainstay of treatment for patients with polymyalgia rheumatica (PMR) and often produce substantial clinical improvements, but treatment can be complicated by relapse, adverse effects of therapies, and concomitant conditions. New recommendations aim to guide clinicians and improve the management of this disorder.

Insulin resistance is closely associated with an increased risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Anti-TNF therapy reduces insulin resistance and improves insulin sensitivity in patients with severe RA. New findings have shown, however, that the efficacy of these agents in this regard is impaired by obesity.

Early diagnosis is critical to reduce the risk of visual impairment in patients with giant cell arteritis. A report on the guidelines for the management of this disease offers practical recommendations; however, further efforts that incorporate collaborative multicenter studies might be needed to reach agreement among clinicians.

New data highlight the contribution of IL-6 to vascular calcification in chronic inflammation. Given that increased vascular calcification and accelerated atherosclerosis occur in patients with chronic inflammatory diseases, new therapies that block the IL-6 pathway might reduce the risk of cardiovascular events in these patients.

Rheumatoid arthritis (RA) and metabolic syndrome share several pathologic characteristics, such as changes in body composition, lipid levels and insulin sensitivity, that may increase cardiovascular mortality. Here, Kerekes and co-authors discuss associations between these components in RA and metabolic syndrome and propose that optimal therapeutic control of RA might attenuate adverse effects of metabolic syndrome in patients with RA.

Rheumatoid diseases such as rheumatoid arthritis are associated with accelerated atherosclerosis, increased cardiovascular morbidity and mortality. The early signs of cardiovascular disease therefore need to be recognized in these patients so that effective cardiovascular protection can be introduced. In this Review the authors discuss validated techniques that are currently available to determine subclinical atherosclerosis in patients with rheumatic conditions.

Ankylosing spondylitis is a common, highly inheritable inflammatory arthritis with poorly understood biology. Here Brown, Cortes and colleagues use fine mapping of the major histocompatibility complex and identify novel associations, and identify other HLA alleles that like HLA-B27 interact with ERAP1 variants to influence disease risk.

Leptin is involved in regulating bone mass, basal metabolism and insulin secretion, among other processes. This Review explores the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and inflammatory rheumatic diseases.

Sjögren’s syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.

Timothy Radstake and Maureen Mayes and colleagues report results of a genome-wide association study of systemic sclerosis. They identify a new susceptibility locus at CD247.

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

Jane Worthington and colleagues use a high-density genotyping chip to identify new susceptibility loci for rheumatoid arthritis and examine genetic overlap with other autoimmune diseases. Their results increase the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry and refine the location of many previously identified association signals to single genes.

Matthew Brown and colleagues identify multiple susceptibility variants for ankylosing spondylitis through an association study based on high-density genotyping of immune-related loci. Their findings implicate numerous biological pathways in the pathogenesis of this disease and highlight shared risk factors with other autoimmune diseases.

A genome-wide association study meta-analysis of more than 100,000 subjects of European and Asian ancestries reveals 42 new risk loci for rheumatoid arthritis, with follow-up studies identifying 98 biological candidate genes that are either already being targeted by drugs or could be in the future.

In this Review, the authors discuss the immunometabolic alterations involved in the pathogenesis of intervertebral disc degeneration, including the role of adipokines in impaired metabolism in intervertebral disc cells, and discuss opportunities for future research and development of new therapies.

WISP-2, a recently identified adipokine, plays a role in modulating the turnover of extracellular matrix in the cartilage, and its downregulation may detrimentally alter the inflammatory environment in osteoarthritic cartilage. The authors also show the participation of Wnt/β-catenin signaling pathway in these processes. Thus, targeting WISP-2 might represent a potential therapeutical approach for degenerative and/or inflammatory diseases of musculoskeletal system, such as osteoarthritis.

In this article the authors demonstrate that monomeric C reactive protein (mCRP) increases NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 expression in chondrocytes. mCRP exerts a sustained catabolic effect on chondrocytes, increasing the expression of inflammatory mediators and proteolytic enzymes, which can promote cartilage extracellular matrix breakdown and osteoarthritis development and progression.