Laboratoire DImmunologie et DImmunomonitoring

Saint-Étienne, France

Laboratoire DImmunologie et DImmunomonitoring

Saint-Étienne, France
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Moreau A.C.,Laboratoire DImmunologie et DImmunomonitoring | Paul S.,Laboratoire DImmunologie et DImmunomonitoring | Del Tedesco E.,Service de Gastrologie Enterologie Hepatologie | Rinaudo-Gaujous M.,Laboratoire DImmunologie et DImmunomonitoring | And 4 more authors.
Inflammatory Bowel Diseases | Year: 2014

Background: A previous meta-analysis suggested that 6-thioguanine nucleotides levels are associated with clinical remission in inflammatory bowel disease. It was criticized because of the relatively small number of patients included in this meta-analysis and heterogeneity between studies. Recent studies provided conflicting results, and the source of those discrepancies has yet to be explored. Methods: A comprehensive, computerized literature search was conducted in Medline, ISI Web of Science, and EMBASE until December 31, 2012. A combined odd ratio with its 95% confidence interval was calculated using a fixed effects model based on the Mantel-Haenszel method. Between-study heterogeneity was assessed using Cochran's Q statistic. Results: Seventeen studies enrolling 2049 patients with inflammatory bowel disease were analyzed. A significant heterogeneity was found in the overall analysis (P = 0.005). As heterogeneity among studies could be explained by differences in metabolite assay methods, an analysis including only studies using the reference method by Lennard et al (N = 10) was performed, and the pooled odds ratio for clinical remission among patients with 6-thioguanine nucleotides levels over a cut-off value between 230 and 260 pmol/8.10 8 RBC was 3.15 (95% confidence interval, 2.41-4.11). Conclusions: This meta-analysis clearly establishes an association between 6-thioguanine nucleotides levels and clinical remission rates in patients with inflammatory bowel disease and explains the heterogeneity of results among selected studies. The lack of standardization in 6-thioguanine nucleotides assays is responsible for recent contradictory results. Whether therapeutic drug monitoring of thiopurines should be systematically used in clinical practice in inflammatory bowel disease to improve disease outcomes will require further investigation. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.


Rinaudo-Gaujous M.,Laboratoire dImmunologie et dImmunomonitoring | Paul S.,Laboratoire dImmunologie et dImmunomonitoring | Tedesco E.D.,Service de Gastrologie Enterologie Hepatologie | Genin C.,Laboratoire dImmunologie et dImmunomonitoring | And 2 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013

Background: A biosimilar is a copy version of an approved original biological medicine whose data protection has expired. Aim: To provide an overview of the development of biosimilars worldwide. Methods: Literature review of manufacturing processes of biosimilars, differences and similarities between biosimilars and the reference product, approval pathways for biosimilars, challenges in clinical trial study design and available data from clinical trials. Results: Biosimilars have the same amino acid sequence and highly similar glycosylation patterns that overlap with the originator product. Both efficacy and toxicity are difficult to predict due to subtle molecular changes that might have profound effects on clinical efficacy, safety and immunogenicity. Their main advantage is related to cost savings. Direct evidence of safety and benefit from clinical trials, post-marketing pharmacoviligance and unequivocal identification of the product as a biosimilar are requirements before approval. Non-inferiority or equivalence trials are required by regulatory agencies. Over the past years, several biosimilars have been approved such as erythropoietin or growth factors. Recently, two monoclonal antibodies, Remsima and Inflectra, have been shown to be equivalent to infliximab (INX) in safety and efficacy in rheumatologic conditions. Interchangeability, automatic substitution and switching are key issues when treating patients with biosimilars in clinical practice. Conclusions: Biosimilars represent a new generation of drugs in liver and gastrointestinal diseases. On June 27, 2013, Hospira's Inflectra (INX) was the first biosimilar monoclonal antibody to receive positive opinion from European Medicines Agency's Committee for Medicinal Products for Human Use for rheumatoid arthritis, inflammatory bowel disease and plaque psoriasis. © 2013 John Wiley & Sons Ltd.


Paul S.,Laboratoire dImmunologie et dImmunomonitoring | Del Tedesco E.,Service de Gastrologie Enterologie Hepatologie | Marotte H.,Service de Rhumatologie | Rinaudo-Gaujous M.,Laboratoire dImmunologie et dImmunomonitoring | And 5 more authors.
Inflammatory Bowel Diseases | Year: 2013

Background: Data on the value of therapeutic drug monitoring of infliximab (IFX) to predict mucosal healing (MH) in inflammatory bowel diseases (IBD) are scarce. Methods: All consecutive patients with IBD receiving ongoing IFX (5 mg/kg) treatment and developing secondary failure to IFX were enrolled in a prospective study between June 2010 and May 2011. IFX trough levels, antibodies to IFX concentrations, C-reactive protein levels, and fecal calprotectin were measured before IFX optimization and at week 8. A proctosigmoidoscopy was performed on the day of first IFX optimization and at week 8 in all patients with ulcerative colitis (UC). MH was defined by fecal calprotectin <250 μg/g stools in Crohn's disease (CD) and by an endoscopic Mayo score of 0 or 1 in UC. Results: This study included 52 patients with IBD: 34 patients with CD (mean Crohn's Disease Activity Index, 300; mean C-reactive protein, 28 ± 10 mg/L; mean fecal calprotectin, 705 ± 300 mg/g) and 18 patients with UC (mean Simple Clinical Colitis Activity Index, 7; mean Mayo endoscopic score, 3). After IFX dose intensification, half of CD and UC patients achieved MH. Increase in IFX trough levels (called "delta IFX" in micrograms per milliliter) was associated with MH in both CD and UC (P = 0.001). A delta IFX >0.5 μg/mL was associated with MH (sensitivity [se], 0.88; specificity [sp], 0.77; P = 0.0001, area under the receiver operating characteristic curve, 0.89). On multivariate analysis, the only factor associated with MH after IFX optimization was a delta IFX >0.5 μg/mL (likelihood ratio = 2.02; 95% confidence interval, 1.01-4.08; P = 0.048) in patients with IBD. Conclusions: Therapeutic drug monitoring of IFX strongly predicts the likelihood of achieving MH following IFX dose intensification in both CD and UC. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.


Paul S.,Laboratoire dImmunologie et dImmunomonitoring | Moreau A.C.,Laboratoire dImmunologie et dImmunomonitoring | Del Tedesco E.,Service de Gastrologie Enterologie Hepatologie | Rinaudo M.,Laboratoire dImmunologie et dImmunomonitoring | And 4 more authors.
Inflammatory Bowel Diseases | Year: 2014

Background: The aim of this meta-analysis was to explore the magnitude of the association between pharmacokinetics of adalimumab and clinical response in patients with inflammatory bowel disease. Methods: A literature search was performed up to December 2013. MEDLINE, EMBASE, Cochrane, and meeting abstracts were reviewed. Studies were included if they analyzed the association of trough levels of adalimumab (TRA) or antibodies against adalimumab (AAA) with clinical response in adult or pediatric inflammatory bowel disease. A Mantel-Haenszel pooled risk estimate provided a measure of the association. Results: Fourteen studies enrolling 1941 patients with inflammatory bowel disease were included in the systematic review. Thirteen studies analyzed clinical outcomes according to TRA. In only 1 study, there was no correlation between high TRA and clinical response. Six of the 7 studies reported a negative correlation between AAA and clinical outcomes. Six studies enrolling 536 patients (Crohn's disease [CD] only) met the meta-analysis inclusion criteria. The pooled odds ratio (OR) for loss of clinical response to adalimumab in patients with CD (N = 4) with positive AAAs was 10.15 (95% confidence interval [CI]: 3.90-26.40, P < 0.0001). Patients with CD with TRA over a predefined cutoff were more likely to be in clinical remission with an OR of 2.6 (95% CI: 1.79-3.77, P < 0.0001). The association was stronger if the analysis was limited to the adult population (N = 3, OR: 7.05, 95% CI: 3.58-13.9, P < 0.0001). Conclusions: The presence of AAA is associated with a higher risk of loss of clinical response to adalimumab, whereas high TRA is associated with greater clinical response rates in CD. More data are needed in ulcerative colitis. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.


Launay O.,University of Paris Descartes | Launay O.,French Institute of Health and Medical Research | Paul S.,REseau national dInvestigation clinique en VACcinologie | Paul S.,Laboratoire dimmunologie et dimmunomonitoring | And 18 more authors.
Vaccine | Year: 2013

Background: CXCR4 is a chemokine receptor with multiple effects on the immune system, upregulated in patients with SLE, and correlated with disease severity. Objective: This study has investigated whether the levels of CXCR4 expressed on leucocyte subsets in lupus patients are correlated with the efficacy and the safety of the influenza vaccine. Methods: Twenty-seven patients were vaccinated and vaccine immunogenicity and tolerance were evaluated. CXCR4 was assayed on leucocyte subsets and correlated with clinical and immunological signs of diseases activity. Results: A significant increase in the titres of antibodies to the three viral strains was observed along with trends towards an increased vaccine efficacy in patients with quiescent disease vs patients with active disease. Recent flu vaccine history and, to a lesser extent, immunosuppressive treatment may influence vaccine immunogenicity. Influenza immunization was not associated with clinical side-effects or clinical lupus flare but with an increase in rheumatoid factor levels. Our study also confirms the correlation of CXCR4 expression with biological autoimmunity as shown by the correlation between the percentage of CXCR4-positive T cells and the ANA titres at D0, and the reverse correlation between CXCR4 expression and vaccine immunogenicity as demonstrated by the higher percentage of CXCR4-positive T cells at D0 and D30 in non-responders vs responders. Conclusion: Altogether, our study confirms the efficacy and the safety of flu vaccine in SLE patients, highlights the role of CXCR4 as a surrogate marker for autoimmunity in lupus and shows that CXCR4 expression on T cells is predictive of vaccine efficacy in SLE patients. © 2013 The Authors.

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