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Prey S.,Bordeaux University Hospital Center | Prey S.,University of Bordeaux 1 | Prey S.,French Institute of Health and Medical Research | Ezzedine K.,Bordeaux University Hospital Center | And 32 more authors.
British Journal of Dermatology | Year: 2012

Background Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-β signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes. Objectives We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis. Methods We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention. Results Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30-71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. -0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups. Conclusions This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements. © 2012 The Authors. BJD © 2012 British Association of Dermatologists. Source


Neel A.,Nantes University Hospital Center | Henry B.,Nantes University Hospital Center | Barbarot S.,Nantes University Hospital Center | Masseau A.,Nantes University Hospital Center | And 37 more authors.
Autoimmunity Reviews | Year: 2014

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9. years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5. years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36. months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6. mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown. © 2014 Elsevier B.V. Source


Deram A.,University of Lille Nord de France | Genin M.,University of Lille Nord de France | Noel C.,Service de Nephrologie | Cuny D.,University of Lille Nord de France | And 85 more authors.
PLoS ONE | Year: 2014

Background: Strong geographic variations in the incidence of end-stage renal disease (ESRD) are observed in developed countries. The reasons for these variations are unknown. They may reflect regional inequalities in the populations sociodemographic characteristics, related diseases, or medical practice patterns. In France, at the district level, the highest incidence rates have been found in the Nord-Pas-de-Calais region. This area, with a high population density and homogeneous healthcare provision, represents a geographic situation which is quite suitable for the study, over small areas, of spatial disparities in the incidence of ESRD, together with their correlation with a deprivation index and other risk factors.Methods: The Renal Epidemiology and Information Network is a national registry, which lists all ESRD patients in France. All cases included in the Nord-Pas-de-Calais registry between 2005 and 2011 were extracted. Adjusted and smoothed standardized incidence ratio (SIR) was calculated for each of the 170 cantons, thanks to a hierarchical Bayesian model. The correlation between ESRD incidence and deprivation was assessed using the quintiles of Townsend index. Relative risk (RR) and credible intervals (CI) were estimated for each quintile.Results: Significant spatial disparities in ESRD incidence were found within the Nord-Pas-de-Calais region. The sex- and ageadjusted, smoothed SIRs varied from 0.66 to 1.64. Although no correlation is found with diabetic or vascular nephropathy, the smoothed SIRs are correlated with the Townsend index (RR: 1.18, 95% CI [1.00-1.34] for Q2; 1.28, 95% CI [1.11-1.47] for Q3; 1.30, 95% CI [1.14-1.51] for Q4; 1.44, 95% CI [1.32-1.74] for Q5).Conclusion: For the first time at this aggregation level in France, this study reveals significant geographic differences in ESRD incidence. Unlike the time of renal replacement care, deprivation is certainly a determinant in this phenomenon. This association is probably independent of the patients financial ability to gain access to healthcare. © 2014 Occelli et al. Source

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