Rheumatoid arthritis is getting less frequent—results of a nationwide population-based cohort study

Objectives: The objectives of this study were to examine changes in incidence and prevalence of RA between 1990 and 2014, and to explore if there is any geographic variation in incidence and prevalence of RA in the UK Methods: Design Prospective cohort study Setting Primary care Participants People contributing acceptable data to Clinical Practice Research Datalink (CPRD) between 01/01/1990 and 31/12/2014 were included. Read codes were used to identify RA cases ≥18 years in age. Outcomes Prevalence and incidence rates for each year standardised to the 2014 population. Region specific incidence and prevalence of RA for the year 2014 standardized to the overall population. Results: The incidence and prevalence of RA was 3.81 per 10,000 person-years and 0.67% respectively in 2014. The annual incidence of RA reduced by -1.6%(-0.8% to - 2.5%) between 1990 and 2014, with significant joinpoints at 1994 and 2002. The prevalence of RA increased by 3.7%(3.2% to 4.1%)/year from 1990 to 2005; and reduced by -1.1%(-2.0% to -0.2%)/year between 2005 and 2014. There were significant differences in the occurrence of RA throughout different regions of the UK, with highest incidence in East Midlands, Yorkshire and Humber; and highest prevalence in North East, and Yorkshire and Humber. Conclusion: The incidence of RA is decreasing, with a reduction in prevalence in recent years. There is significant geographic variation in occurrence of RA in UK. Further research is required to identify the reasons underlying this phenomenon so that public-health interventions can be designed to further reduce the incidence of RA

Glycoprotein YKL-40 : A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial

Objective YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission. Methods Ninety-nine patients with early DMARD-naive RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay. Results At the baseline, plasma YKL-40 concentration was 57 +/- 37 ( mean +/- SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-alpha antagonist infliximab was added on the combination treatment. Conclusions High YKL-40 levels were found to be associated with disease activity in early DMARD-naive RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.Peer reviewe

Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial

ObjectiveYKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission.MethodsNinety-nine patients with early DMARD-naive RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay.ResultsAt the baseline, plasma YKL-40 concentration was 57 +/- 37 ( mean +/- SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-alpha antagonist infliximab was added on the combination treatment.ConclusionsHigh YKL-40 levels were found to be associated with disease activity in early DMARD-naive RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission

Clinical Characteristics and Outcomes of Juvenile and Adult Dermatomyositis

Dermatomyositis (DM) is an idiopathic inflammatory myopathy with bimodal onset age distribution. The age of onset is between 5-18 yr in juvenile DM and 45-64 yr in adult DM. DM has a distinct clinical manifestation characterized by proximal muscle weakness, skin rash, extramuscular manifestations (joint contracture, dysphagia, cardiac disturbances, pulmonary symptoms, subcutaneous calcifications), and associated disorders (connective tissue disease, systemic autoimmune diseases, malignancy). The pathogenesis of juvenile and adult DM is presumably similar but there are important differences in some of the clinical manifestations, associated disorders, and outcomes. In this study, we investigated the clinical characteristics and outcomes of 16 patients with juvenile DM and 48 with adult DM. This study recognizes distinctive characteristics of juvenile DM such as higher frequency of neck muscle involvement, subcutaneous calcifications, and better outcomes

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD