Significant advances in our understanding of RA and its management have been made in the past decade, resulting in earlier intervention with biologic DMARDs, particularly in patients with evidence of aggressive, erosive disease. Here, one such biologic therapy, the T-cell co-stimulation modulator abatacept, is discussed, exploring clinical evidence published to date on its use in patients with very early arthritis/early RA who are MTX naïve, and in patients with established RA and an inadequate response to MTX or TNF antagonists. Data from relevant clinical trials are overviewed, discussing the clinical efficacy of abatacept in early disease, the clinical outcomes over long-term treatment in different patient populations and the effects of abatacept on structural damage. Findings from integrated safety analyses of abatacept clinical trial data, representing 10,366 patient-years of exposure are described, and clinically important safety events, including serious infections, malignancies and autoimmune events, are highlighted. It is concluded that abatacept represents an effective treatment option with an established safety profile across different patient populations, including patients with both early and erosive RA and those with established disease. Furthermore, efficacy data from studies in patients with early disease suggest that the risk-benefit profile of abatacept may be more favourable when introduced earlier in the treatment paradigm.

Biological agents, including TNF inhibitors, have revolutionized the treatment of RA in recent years. Certolizumab pegol (CZP) is a novel pegylated anti-TNF approved for the treatment of adult patients with moderately to severely active RA. This article provides an overview of three published clinical trials of CZP in RA in patients with active disease who have shown an inadequate response to DMARDs, including MTX: RA prevention of structural damage (RAPID) 1 and 2, which evaluated the efficacy and safety of CZP added to MTX when dosed every 2 weeks, and efficacy and safety of CZP - 4 weekly dosage in rheumatoid arthritis (FAST4WARD), which evaluated CZP monotherapy when dosed every 4 weeks. In the trials, CZP plus MTX or as monotherapy significantly improved the signs and symptoms of RA and RA disease activity, and CZP plus MTX significantly inhibited the progression of radiographic joint damage as early as Week 16 of the treatment. In addition, CZP treatment significantly improved patient-reported outcome measures, providing significant reductions in pain and fatigue and improvements in physical function as early as Week 1 of treatment; improvements in health-related quality of life were evident at the first assessment at Week 12. CZP treatment improved productivity at work, significantly reducing the number of days of missed work as well as the number of days with reduced productivity, and also increased productivity within the home and improved participation in family, social and leisure activities. CZP was generally well tolerated when used either as monotherapy or added to MTX; most adverse events were mild or moderate. Taken together, the results of these trials suggest that CZP is an effective new option for the treatment of RA.

The Lupus Family Registry and Repository (LFRR) was established with the goal of assembling and distributing materials and data from families with one or more living members diagnosed with SLE, in order to address SLE genetics. In the present article, we describe the problems and solutions of the registry design and biometric data gathering; the protocols implemented to guarantee data quality and protection of participant privacy and consent; and the establishment of a local and international network of collaborators. At the same time, we illustrate how the LFRR has enabled progress in lupus genetics research, answering old scientific questions while laying out new challenges in the elucidation of the biologic mechanisms that underlie disease pathogenesis. Trained staff ascertain SLE cases, unaffected family members and population-based controls, proceeding in compliance with the relevant laws and standards; participant consent and privacy are central to the LFRR's effort. Data, DNA, serum, plasma, peripheral blood and transformed B-cell lines are collected and stored, and subject to strict quality control and safety measures. Coded data and materials derived from the registry are available for approved scientific users. The LFRR has contributed to the discovery of most of the 37 genetic associations now known to contribute to lupus through 104 publications. The LFRR contains 2618 lupus cases from 1954 pedigrees that are being studied by 76 approved users and their collaborators. The registry includes difficult to obtain populations, such as multiplex pedigrees, minority patients and affected males, and constitutes the largest collection of lupus pedigrees in the world. The LFRR is a useful resource for the discovery and characterization of genetic associations in SLE.

RA is the prototypic chronic inflammatory disease, characterized by progressive articular cartilage and bone destruction. The systemic nature of RA is evidenced by the increased risk of atherosclerosis and lymphoproliferative disorders. Components of both the innate and adaptive immune system are implicated in the pathophysiology of the articular and extra-articular manifestations of the disease. A fundamental process in the onset of RA is the breakdown in self-tolerance. Accelerated ageing of immune cells (immunosenescence) appears to be a major mechanism favouring the disruption of tolerance. Telomere erosion, a hallmark of immunosenescence, is present in lymphoid (naïve and memory T cells) and myeloid (granulocytes) cells in RA. The premature ageing process also involves the haematopoietic stem and progenitor cells (CD34(+) HSPC), thus extending the RA immunopathogenesis to include early events in the shaping of the immune system. This review summarizes current concepts of HSPC ageing and its impact on immune regeneration, highlighting the phenotypic and functional similarities between elderly and RA HSPC.

To document the current state of musculoskeletal US (MSUS) training and extent of implementation among rheumatologists in the member countries of EULAR.

ACPA is a highly specific marker for RA. It was recently reported that ACPA can be used to classify RA into two disease subsets, ACPA-positive and ACPA-negative RA. ACPA-positive RA was found to be associated with the HLA-DR shared epitope (SE), but ACPA negative was not. However, the suspicion remained that this result was caused by the ACPA-negative RA subset containing patients with non-RA diseases. We examined whether this is the case even when possible non-RA ACPA-negative RA patients were excluded by selecting only patients with bone erosion.

SSc (scleroderma) is an often fatal disease characterized by widespread tissue fibrosis. Fibroblasts play a key role in SSc-associated fibrosis. This study was designed to determine: (i) whether fibroblasts isolated from skin of patients with SSc have increased lysophosphatidic acid-activated Cl- current (IClLPA) activity vs healthy controls; (ii) whether myofibroblast differentiation is involved in SSc skin fibrosis; and (iii) whether SSc fibroblasts have different proliferation rates vs controls.

To present the usefulness of a centralized system of data collection for the development of an international multicentre registry of SpA.

The paediatric idiopathic inflammatory myopathies (IIMs) are a group of rare chronic inflammatory disorders of childhood, affecting muscle, skin and other organs. There is a severe lack of evidence base for current treatment protocols in juvenile myositis. The rarity of these conditions means that multicentre collaboration is vital to facilitate studies of pathogenesis, treatment and disease outcomes. We have established a national registry and repository for childhood IIM, which aims to improve knowledge, facilitate research and clinical trials, and ultimately to improve outcomes for these patients.

SSc is an autoimmune disease characterized by fibrosis of the skin and internal organs. Although the aetiology remains uncertain, many reports have suggested that IL-6 is involved in SSc pathogenesis. Tocilizumab, an anti-IL-6 receptor antibody, is an anti-arthritis medicine that works through the blockade of IL-6 functions. To examine the effect of tocilizumab on SSc, we administered tocilizumab to two SSc patients.

To evaluate the person-level impact of weight loss on serum urate levels among men with a high cardiovascular risk profile.

To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes.

Human disorders of hereditary and nonhereditary heterotopic ossification are conditions in which osteogenesis occurs outside of the skeleton, within soft tissues of the body. The resulting extraskeletal bone is normal. The aberration lies within the mechanisms that regulate cell-fate determination, directing the inappropriate formation of cartilage or bone, or both, in tissues such as skeletal muscle and adipose tissue. Specific gene mutations have been identified in two rare inherited disorders that are clinically characterized by extensive and progressive extraskeletal bone formation-fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In fibrodysplasia ossificans progressiva, activating mutations in activin receptor type-1, a bone morphogenetic protein type I receptor, induce heterotopic endochondral ossification, which results in the development of a functional bone organ system that includes skeletal-like bone and bone marrow. In progressive osseous heteroplasia, the heterotopic ossification leads to the formation of mainly intramembranous bone tissue in response to inactivating mutations in the GNAS gene. Patients with these diseases variably show malformation of normal skeletal elements, identifying the causative genes and their associated signaling pathways as key mediators of skeletal development in addition to regulating cell-fate decisions by adult stem cells.

NFκB is a family of transcription factors involved in immunity and the normal functioning of many tissues. It has been well studied in osteoclasts, and new data indicate an important role for NFκB in the negative regulation of bone formation. In this article, we discuss how NFκB activation affects osteoblast function and bone formation. In particular, we describe how reduced NFκB activity in osteoblasts results in an increase in bone formation via enhanced c-Jun N-terminal kinase (JNK) activity, which regulates FOSL1 (also known as Fra1) expression. Furthermore, we discuss how estrogen and NFκB crosstalk in osteoblasts acts to oppositely regulate bone formation. Future NFκB-targeting treatments for osteoporosis, rheumatoid arthritis and other inflammatory bone diseases could lead to increased bone formation concurrent with decreased bone resorption.

Currently, there are no prospective studies exploring the prognosis of patients with juvenile primary FM syndrome (JPFS) or their physical, emotional and social outcomes as they enter the early adult years. The primary objective of this study was to assess long-term outcomes of a paediatric sample of clinically referred JPFS patients and their matched healthy controls.

We examined occupational and non-occupational exposures in relation to risk of SLE in a case-control study conducted through the Canadian Network for Improved Outcomes in SLE (CaNIOS).

To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages.

Anti-TNF therapy has significantly improved outcomes for patients with severe RA. In the UK, changing financial restrictions and increasing experience with their use may have resulted in changes to the way physicians use anti-TNF therapies. The aim of this analysis was to examine changes in disease characteristics and response rates among patients starting anti-TNF therapy for RA over an 8-year period.

To estimate the incidence of, and factors associated with, consultation for musculoskeletal foot problems in primary care.