PubMed | Hospital Universitario La Paz, Mauriziano Hospital, Rheumatology Center, Santa Maria della Misericordia Hospital and 20 more.
Type: Review | Journal: Clinical reviews in allergy & immunology | Year: 2016
Anti-Jo-1 is the most frequently detectable antibody in the antisynthetase syndrome (ASSD), an autoimmune disease characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). Recently, we organized an international collaborative group called American and European NEtwork of Antisynthetase Syndrome (AENEAS) for the study of this rare and fascinating disease. The group collected and published one of the largest series of ASSD patients ever described and with one of the longer follow-up ever reported. The number of participating centers is steadily increasing, as well as the available cohort. In the first paper, we showed that arthritis, myositis, and ILD may be frequently the only feature at disease onset, raising problems to reach a correct diagnosis of this syndrome. Nevertheless, we first observed that the ex novo appearance of further manifestations is common during the follow-up, strengthening the importance of a correct diagnosis. In our cohort, the 24% of the 243 patients up to now collected had isolated arthritis as a presenting feature. These patients represent the most intriguing group in terms of differential diagnosis and clinical time course. Furthermore, data on this aspect are scanty, the reason that lead us to evaluate these aspects in our cohort of patients, reviewing also available literature. In fact, the most relevant aspect is that ASSD is rarely suspected in this setting of patients, in particular in case of poliarticular involvement, positive rheumatoid factor (RF), or anti-cyclic citrullinated peptide antibodies (ACPA) or evidence of joint erosions at plain radiographs. These findings were not rare in our cohort, and they have been also described in other series. Furthermore, manifestations such as Raynauds phenomenon, mechanics hands, and fever that may lead to the suspect of ASSD are observed only in a third of cases. If we consider the high rate of clinical picture progression in these patients, we feel that ASSD should be carefully considered in all patients presenting with isolated arthritis, even in those with erosive, RF, and ACPA-positive arthritis.
Maheu E.,St Antoine Hospital |
Cadet C.,Rheumatology Center |
Marty M.,Henri Mondor Hospital |
Moyse D.,DM Consultant |
And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2014
Objective: To assess the ability of avocado-soybean unsaponifiable- Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). Methods: Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of 'progressors' (JSW loss≥0.5 mm) between groups. Results: 399 patients were randomised (345 kept in the FAS), aged 62 (35-84) years, 54% women, mean body mass index 27 (SD 4) kg/m2, mean symptom duration 4 (SD 5) years, 0-100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (-0.638 mm vs -0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. Conclusions: 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment. Trial registration number on ClinicalTrial.gov NCT01062737.
Johnson S.R.,University of Toronto |
Naden R.P.,Auckland City Hospital |
Fransen J.,Radboud University Nijmegen |
Van Den Hoogen F.,Rheumatology Center |
And 26 more authors.
Journal of Clinical Epidemiology | Year: 2014
Objectives Classification criteria for systemic sclerosis (SSc) are being developed. The objectives were to develop an instrument for collating case data and evaluate its sensibility; use forced-choice methods to reduce and weight criteria; and explore agreement among experts on the probability that cases were classified as SSc. Study Design and Setting A standardized instrument was tested for sensibility. The instrument was applied to 20 cases covering a range of probabilities that each had SSc. Experts rank ordered cases from highest to lowest probability; reduced and weighted the criteria using forced-choice methods; and reranked the cases. Consistency in rankings was evaluated using intraclass correlation coefficients (ICCs). Results Experts endorsed clarity (83%), comprehensibility (100%), face and content validity (100%). Criteria were weighted (points): finger skin thickening (14-22), fingertip lesions (9-21), friction rubs (21), finger flexion contractures (16), pulmonary fibrosis (14), SSc-related antibodies (15), Raynaud phenomenon (13), calcinosis (12), pulmonary hypertension (11), renal crisis (11), telangiectasia (10), abnormal nailfold capillaries (10), esophageal dilation (7), and puffy fingers (5). The ICC across experts was 0.73 [95% confidence interval (CI): 0.58, 0.86] and improved to 0.80 (95% CI: 0.68, 0.90). Conclusions Using a sensible instrument and forced-choice methods, the number of criteria were reduced by 39% (range, 23-14) and weighted. Our methods reflect the rigors of measurement science and serve as a template for developing classification criteria. © 2014 Published by Elsevier.
Genovese M.C.,Stanford University |
Bojin S.,County Hospital |
Biagini I.M.,County Hospital |
Mociran E.,County Hospital |
And 4 more authors.
Arthritis and Rheumatism | Year: 2013
Objective Tabalumab, a fully human IgG4 monoclonal antibody, neutralizes soluble and membrane-bound BAFF. The aim of this study was to examine the tolerability and efficacy of tabalumab in patients with active rheumatoid arthritis receiving methotrexate. Methods In this randomized, double-blind, placebo-controlled, parallel, multiple-dose study, patients who were naive to biologic therapy received infusions of tabalumab (30, 60, or 160 mg) or placebo at weeks 0, 3, and 6 in combination with methotrexate and were evaluated for 24 weeks. The primary efficacy end point was the percentage of patients meeting American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. Results At week 16, the percentages of patients achieving an ACR20 response in the 30-mg (57.6%), 60-mg (67.6%), and 160-mg (51.5%) groups were significantly greater than the percentage of patients achieving an ACR20 response in the placebo group (29.4%; P < 0.05). There were initial transient increases from baseline in the frequency of CD20+ and IgD+/CD27- B cells, followed by reductions, although B cells were not completely depleted. Also, the frequency of IgD-/CD27+ B cells increased in all tabalumab groups compared with the placebo group and returned toward baseline levels by the end of the study. The incidence of adverse events was similar across all treatment groups; no deaths occurred. Serum IgM levels decreased significantly in all tabalumab groups combined compared with the placebo group. There were no significant decreases in serum IgG or IgA levels in the tabalumab groups compared with the placebo group. Conclusion Tabalumab treatment significantly reduces the signs and symptoms of rheumatoid arthritis and has a safety profile similar to that seen with placebo treatment. Copyright © 2013 by the American College of Rheumatology.
Gamazon E.R.,University of Chicago |
Gamazon E.R.,Vanderbilt University |
Wheeler H.E.,University of Chicago |
Shah K.P.,University of Chicago |
And 9 more authors.
Nature Genetics | Year: 2015
Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual's genetic profile and correlates 'imputed' gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys the benefits of gene-based approaches such as reduced multiple-testing burden and a principled approach to the design of follow-up experiments. Our results demonstrate that PrediXcan can detect known and new genes associated with disease traits and provide insights into the mechanism of these associations. © 2015 Nature America, Inc. All rights reserved.
PubMed | Rheumatology Center, Vanderbilt University and University of Chicago
Type: Journal Article | Journal: Nature genetics | Year: 2015
Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individuals genetic profile and correlates imputed gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys the benefits of gene-based approaches such as reduced multiple-testing burden and a principled approach to the design of follow-up experiments. Our results demonstrate that PrediXcan can detect known and new genes associated with disease traits and provide insights into the mechanism of these associations.
Gromnica-Ihle E.,Rheumatology |
Kruger K.,Rheumatology Center
Clinical and Experimental Rheumatology | Year: 2010
Methotrexate (MTX) is one of the most commonly used drugs in the treatment of inflammatory rheumatic diseases. Unfortunately, MTX is an FDA Pregnancy Category X medication, which means it is contraindicated during pregnancy. The following review of the literature, with international guidelines, gives in addition an overview of current scientific knowledge on the topic. MTX is a teratogenic substance. It accesses the placenta and, for the dosage of 5 to 25mg per week normally used in rheumatic diseases, can lead to both habitual abortions and anomalies in the neonate. Folic acid antagonism of MTX is the reason. In the rheumatologic setting, small case reports are available for the usage of MTX of 101 pregnant women at the time of conception or during pregnancy, mostly during the first trimester. Individual casuistry also exists. An abortion rate of 23% was found to result from these case reports. The anomaly rate for neonates was >5%. Only a few pregnancies with neonatal anomalies are described with the child's father taking MTX at the time of conception. MTX is taken up (in small amounts) by the mother's milk, and breast feeding under MTX therapy, therefore, is also contraindicated. Detailed and exact information on female patients taking MTX during the reproduction phase, but also for the father-to-be of the child if treated with MTX, with reference to the required contraception until at least three months before a planned conception and stopping of MTX at least at that time, is essential. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2010.
Eijsbouts A.M.M.,Rheumatology Center |
Kempers M.J.E.,Radboud University Nijmegen |
van den Hoogen F.H.J.,Rheumatology Center |
Laan R.F.J.M.,Radboud University Nijmegen |
And 4 more authors.
Clinical and Experimental Rheumatology | Year: 2011
Objective: To study the effects of antirheumatic drugs on hypothalamic-pituitary-adrenal (HPA) axis activity in patients with rheumatoid arthritis (RA). Methods: Twenty patients with recent-onset active RA were studied before antirheumatic treatment, after 2 weeks of naproxen, and after 5 1/2 months of additional treatment with sulphasalazine or methotrexate. The results before treatment were compared with those obtained in 20 age and sex-matched healthy controls (HC). Activity of the HPA-axis was assessed under basal conditions and during insulin tolerance tests (ITT). The ex-vivo production of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α) and IL-6 in whole blood samples was measured with and without stimulation by LPS. Results At baseline, plasma ACTH and cortisol levels were not different between patients with RA and HC. The unstimulated production of IL-6 was significantly higher in RA patients than in HC. After 2 weeks of treatment with naproxen, urinary cortisol excretion decreased significantly (p=0.03), and the area under the curve for plasma cortisol during the ITT was significantly lower (p=0.015). The LPS stimulated production of IL-1β was significantly lower compared with baseline. After 6 months, basal plasma, salivary and urinary cortisol levels, and plasma cortisol and ACTH levels during the ITT, were all unchanged in comparison to the pre-treatment period. The unstimulated ex-vivo production of IL-1β was significantly lower than before treatment. Conclusion: Our results suggest that the non-steroidal anti-inflammatory drug naproxen suppresses the HPA-axis in the first weeks of treatment. After 6 months, this suppressive effect is no longer present, suggesting the existence of adaptive mechanisms. © Clinical and Experimental Rheumatology 2011.