Guillaume Moulis - Academia.edu (original) (raw)

Papers by Guillaume Moulis

American journal of hematology, Jan 27, 2017

The clinical epidemiology of immune thrombocytopenia (ITP) is not well known in adults. This stud... more The clinical epidemiology of immune thrombocytopenia (ITP) is not well known in adults. This study was aimed at assessing the clinical epidemiology of incident ITP adults, the factors associated with chronicity and exposure to treatments. This study was conducted in the CARMEN registry, a multicentric prospective cohort aimed at including all newly diagnosed ITP adults in the French Midi-Pyrénées region, South of France (3 million inhabitants) from June 2013. Descriptive analyses and multivariate logistic regression models were conducted. Out of 121 newly diagnosed ITP until December 2014, 113 patients were followed in the region and gave informed consent. Median age was 65 years. Half of the patients were female, 20.3% had a secondary ITP, 50.4% had a Charlson's score ≥1, median platelet count was 17 x10(9) /L; 50.9% had bleeding symptoms, including 2 severe gastro-intestinal tract and 1 intracranial bleedings; 21.4% had another autoimmune disease and 20.3% experienced an infec...

Pharmacoepidemiology and Drug Safety, 2016

The identification of infections in electronic health databases is a key issue for pharmacoepidem... more The identification of infections in electronic health databases is a key issue for pharmacoepidemiology research. The aim of this study was to assess the positive predictive values (PPVs) of hospitalizations for infection in the Système National d'Information Inter-régimes de l'Assurance Maladie, that is the electronic database recording in-and-out hospital data for the entire French population (66 million inhabitants). The source of data was the database of hospitalizations (Programme de Médicalisation des Systèmes d'Informations) of Toulouse University hospital, South of France (2880 beds). Among all hospital stays between September and December 2014, we randomly selected 100 stays with an International Classification of Diseases, 10th revision code of infection as primary diagnosis and 100 as related diagnosis. Medical charts were reviewed to assess the PPV of infection codes, as well as the PPV of correct coding of infection type among the true positive cases. The PPVs of codes of infection as reason for hospitalization were 0.97, 95% confidence interval (CI) [0.93-1.00] for primary diagnosis codes and 0.70, 95% CI [0.61-0.71] for related diagnosis codes. Among the true positive cases, the PPVs of correct coding of the type of infection were, respectively, 0.98, 95% CI [0.95-1.00] and 0.93, 95% CI [0.88-0.98]. Hospitalizations for infection codes have very good PPVs in the Programme de Médicalisation des Systèmes d'Informations. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacoepidemiology and drug safety, Jan 15, 2017

The risk of venous thromboembolic event (VTE) in multiple myeloma is particularly increased. Curr... more The risk of venous thromboembolic event (VTE) in multiple myeloma is particularly increased. Current guidelines recommend systematic VTE prophylaxis with vitamin K antagonists (VKA) or low weight molecular heparin (LWMH) or unfractionated heparin (UFH) in high-risk patients, based on treatment received [e.g. use of IMiDs (thalidomide, lenalidomide and pomalidomide), alkylating agents or erythropoietin] and individual risk factors (e.g. history of VTE). The aim of this study was to describe strategy of VTE prophylaxis and prescribing of other antithrombotic agents during the first 6 months of multiple myeloma therapy, with stratification on IMiD-based regimens and drug and disease-related risk factors. A retrospective cohort study of French beneficiaries from the health insurance database (SNIIRAM, Système National d'Information Inter-Régime de l'Assurance Maladie) was designed in the Midi-Pyrénées area (South West France). Patients starting a treatment for multiple myeloma i...

Rheumatology, 2016

Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biolo... more Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment. We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement. A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of &amp;amp;amp;amp;amp;amp;amp;lt;60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m(2) at baseline, P &amp;amp;amp;amp;amp;amp;amp;lt; 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study. Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.

American journal of hematology, Jan 16, 2016

$Research paper thumbnail of Characteristics, outcome and response to therapy of multirefractory chronic immune thrombocytopenia$

Blood, Jan 27, 2016

Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to ... more Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. We included, in this multicenter study, 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim and eltrombopag. As compared with an historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (OR 4.84, 95% CI [1.31-17.86], p=.018) and monoclonal gammopathy of undetermined significance (OR 5.94, 95% CI [1.08-32.48], p=.04). The median duration of ITP before being recognized as multirefractory was 78 months (range 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range 6-15). At the end of follow-up (median 84 months [range 12-455]), only 1/14 patients achieved response with immunosuppressa...

In this study, we aimed to provide an updated overview of drug data contained in the French healt... more In this study, we aimed to provide an updated overview of drug data contained in the French health insurance database (SNIIRAM) and its associated national representative sample (EGB). This paper identified most common problems concerning drug data: (i) change in level of coverage of drugs of interest (drug no more eligible for reimbursement, or no more prescription-only), (ii) break in patient eligibility (in connection with change of healthcare plan or patients’ identifier), and (iii) technical and regulatory issues. We provide a brief checklist to enable a structured identification of these issues. The impact of gap in drug data availability on study validity will depend on the research question, drug, setting and population of interest. The French health insurance database and associated sample are valuable resources for pharmacoepidemiological research. There is a need to pursue further methodological and validation studies to promote accurate and transparent use of French health insurance databases for pharmacoepidemiology.

Data Revues 02488663 V30ss4 S0248866309008959, Nov 30, 2009

Clinical and Experimental Rheumatology, Jan 14, 2014

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis. Osseous involvement is the m... more Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis. Osseous involvement is the most frequent feature with bilateral and symmetric osteosclerotic changes in long bone diaphyseal and metaphyseal regions, classically sparing epiphyses. 99mTc scintigraphy shows bilateral and symmetrical metaphysal and diaphyseal increased uptake in almost all the patients, even asymptomatic. Other classical features on CT-scan, very evocative of Erdheim-Chester disease, must be recognised: e.g. 'coated' aorta, 'hairy kidney' patterns. New imaging techniques such as MRI have led to a better description of cardiac and central nervous system involvements. Pachymeningitis and right atrium wall infiltration are new evocative images of this disease. Fluorodeoxyglucose Positron Emission Tomography in the diagnosis or prognosis assessment is still discussed. The objective of this review is to discuss the place of each imaging technique in Erdheim-Chester disease in 2013.

European Journal of Internal Medicine, 2016

PLOS ONE, 2016

To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurre... more To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

Data Revues 02488663 Unassign S0248866313006243, Oct 9, 2013

ABSTRACT Meta-analysis is aimed at assessing an exhaustive, unbiased, reproducible, quantified an... more ABSTRACT Meta-analysis is aimed at assessing an exhaustive, unbiased, reproducible, quantified and accurate synthesis of a research problem. It is sustained by a systematic review of the literature and has statistical particularities. Sources of error and bias are numerous. In this paper, we describe them following the methodology steps of a well-conducted meta-analysis. Causes of divergent conclusions of meta-analyses are described and illustrated with the example of cancer risk assessment in TNF inhibitor-treated rheumatoid arthritis patients. Eventually, this article provides key-points to help readers to detect sources of error and bias in meta-analyses.

Fundamental & Clinical Pharmacology, 2015

We aimed at detecting a signal of an increased risk of cancer in patients treated with TNF-inhibi... more We aimed at detecting a signal of an increased risk of cancer in patients treated with TNF-inhibitor (TNFi) and non-biologic immunosuppressant (NBIS), compared with NBIS alone for auto-immune diseases. Secondly, we aimed at comparing this risk between the different TNFis. We conducted a disproportionality analysis (case/non-case study) from the French National PharmacoVigilance Database. We selected all the reports of serious adverse drug reactions from 2000 to 2010 in patients treated with NBIS for labeled indications of TNFi. Cases were all the reports of cancer that occurred after a minimal three-month exposure to NBIS. Non-cases were all the other reports. We searched for exposure to TNFi and calculated Reporting Odds Ratios (ROR), stratified by condition and type of cancer and adjusted by age, gender, history of cancer, type of NBIS and year of reporting. Out of the 1,918 reports included in the study population, 217 were cases (135 solid and 82 blood cancers). A safety signal was found in rheumatoid arthritis (RA) (ROR: 5.43, 95%CI[3.52-8.38]) particularly for non-melanoma skin cancer (NMSC) (20.17[2.49-163.36]), and in psoriasis/psoriatic arthritis (3.45[1.09-10.92]). No signal was found in Inflammatory Bowel Diseases (IBD) and ankylosing spondylitis, whatever the type of cancer. There was no difference between TNFis. This study puts the argument of an increased risk of cancer (particularly NMSC) in rheumatoid arthritis patients exposed to TNFi and NBIS compared with NBIS alone but not in IBD and ankylosing spondylitis patients. No signal was detected for melanoma potentially related to the lack of power. The signal seems similar whatever the TNFi. This article is protected by copyright. All rights reserved.

Autoimmunity Reviews, 2015

Immune thrombocytopenia (ITP) is an autoimmune disorder leading to bleeding [1]. However, a highe... more Immune thrombocytopenia (ITP) is an autoimmune disorder leading to bleeding [1]. However, a higher risk of thrombosis has been demonstrated in these patients [2-7]. Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β2GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40-10.99]; it was 2.14, 95% CI [1.11-4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-β2GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies.

Le tocilizumab, anticorps monoclonal humanisé inhibiteur de l'interleukine-6, a reçu en 2009 une ... more Le tocilizumab, anticorps monoclonal humanisé inhibiteur de l'interleukine-6, a reçu en 2009 une autorisation de mise sur le marché pour le traitement de la polyarthrite rhumatoïde (PR) en échec des traitements de fond classiques (méthotrexate, léflunomide, etc.) et/ou des anti-TNF-␣, en association avec le méthotrexate. Il est commercialisé sous le nom de RoActemra ® . Le médicament est prescrit par voie intraveineuse tous les mois. Dans la PR, le tocilizumab a démontré une efficacité en termes de réduction de l'activité de la maladie et de destruction articulaire. Il n'a cependant pas été comparé directement aux anti-TNF-␣ ni aux autres médicaments se positionnant dans la même indication (rituximab, abatacept). Dans les études pré-commercialisation, les évènements indésirables graves sont dominés par les infections (de 3 à 5,7 % patients-années) et les neutropénies sévères (jusqu'à 6,3 %). Une cytolyse hépatique est survenue dans moins de 5 % des cas et une élévation du LDL-cholestérol dans environ 15 %. Il n'y a actuellement pas de signal concernant un sur-risque carcinologique mais ceci devra être confirmé par le suivi de pharmacovigilance. L'IL-6 a des effets pléïotropiques, et son rôle est essentiel dans nombre d'autres maladies dysimmunitaires ou inflammatoires. L'utilisation du tocilizumab pourrait ainsi être étendue dans les prochaines années à d'autres pathologies (arthrite chronique juvénile, maladie de Castelman, lupus systémique, maladie de Still, etc.).

Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim o... more Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n°4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time-window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61–3.83). The dose-effect relation showed that the risk existed from averaged daily doses ≥5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17–3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses.

European Journal of Internal Medicine, 2015

Drug Safety, 2015

Eltrombopag and romiplostim are thrombopoietin receptor agonists (TPO-RAs) marketed for immune th... more Eltrombopag and romiplostim are thrombopoietin receptor agonists (TPO-RAs) marketed for immune thrombocytopenia (ITP). Thrombotic events have been reported with both drugs. This study was aimed at assessing whether there is a signal for differential risks of thrombosis between these two TPO-RAs. We carried out a disproportionality analysis in the World Health Organization global individual case safety report (ICSR) database (VigiBase(®)). We selected all ICSRs with exposure to a TPO-RA between January 2011 and December 2014. We searched for exposures to eltrombopag or romiplostim in thrombosis reports as compared with other ICSRs, and we calculated adjusted reporting odds ratios (aRORs). We identified 5850 ICSRs, including 764 cases of thrombosis. In multivariate analyses, there was a signal for an increased risk of thrombosis (venous or arterial; aROR 1.72, 95 % confidence interval [CI] 1.47-2.02), venous thrombosis (aROR 1.88, 95 % CI 1.53-2.31), arterial thrombosis (aROR 1.54, 95 % CI 1.18-2.00), ischaemic stroke (aROR 1.65, 95 % CI 1.13-2.42) and myocardial infarction (aROR 1.50, 95 % CI 1.05-2.13) with eltrombopag as compared with romiplostim. Restriction to ICSRs reported by physicians led to similar results. However, worldwide dispensing data for romiplostim and eltrombopag were not accessible, so the rates of thrombosis with both drugs were not normalized by the daily defined doses and the generalizability of the results is limited. This study suggests the presence of a signal for an increased risk of thrombosis with eltrombopag compared with romiplostim. These results must be confirmed and quantified by large aetiological pharmacoepidemiological studies.