French health insurance databases are organized since 2003 into a huge digital data warehouse, the Système national d’information inter-régime de l’assurance maladie (SNIIR-AM). It covers the entire ...French population (65 million inhabitants). In order to facilitate studies on more frequent conditions, a random sample of 1/97th of national health system beneficiaries has been built since 2005, called the échantillon généraliste des bénéficiaires (EGB). The aim of this article is to describe the main characteristics of the SNIIR-AM and the EGB, to detail their accessibility according to French law, and to present their strengths and limits. It is illustrated with the most recent studies conducted in these databases. These databases include demographic, out-hospital reimbursement (including drug dispensing), medical (costly long-term diseases, occupational diseases, sick-leaves…), and in-hospital data. All these data are prospectively recorded, individualized, made anonymous and linkable. Consequently, the SNIIR-AM is a very useful data source for epidemiological, pharmacoepidemiological and health economics studies, particularly for rare diseases. The EGB is appropriate for long-term research on more frequent diseases.
Les bases de données de l’assurance maladie sont collectées depuis 2003 dans un vaste entrepôt numérique, le Système national d’information inter-régime de l’assurance maladie (SNIIR-AM). La résultante en est une des plus grandes bases médico-administratives au monde, couvrant 65 millions de personnes. Afin de faciliter l’étude de cohortes de patients atteints de maladies plus fréquentes, un échantillon au 1/97e des assurés à l’assurance maladie a été constitué depuis 2005 : l’échantillon généraliste des bénéficiaires (EGB). L’objectif de cette mise au point est de présenter les grandes lignes de l’architecture du SNIIR-AM et de l’EGB, leurs modalités d’accès, leurs intérêts et leurs limites. Leur potentiel en recherche médicale est illustré par les publications les plus récentes. Ces bases de données contiennent des données démographiques, les données de remboursements des prestations ambulatoires (dont les délivrances de médicaments), les données médicales des régimes de l’assurance maladie (affections de longue durée, maladies professionnelles, arrêts de travail…) et les données hospitalières issues du programme de médicalisation des systèmes d’information. Toutes ces données sont individuelles, prospectivement recueillies, anonymisées et chaînables. Tout cela fait du SNIIR-AM une source de données très intéressante pour la recherche épidémiologique, pharmacoépidémiologique et en économie de la santé, particulièrement pour les maladies rares. L’EGB est particulièrement utile à l’étude des maladies plus fréquentes et sur le long terme.
Abstract Objective To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). Methods We performed a multicenter study of ...main characteristics and outcomes of anti-TNF alpha treatments mainly infliximab (62%), and adalimumab (30%) in 124 BD patients 48% of men; median age of 33.5 (28–40) years. Results Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 0.12–0.89; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 7–36 months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. Conclusion Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).
Summary
Background
Inhibitors of dipeptidyl peptidase (DPP)‐IV have been suspected in the onset of bullous pemphigoid for several years now. However, comparative studies assessing the link between ...DPP‐IV inhibitor exposure and bullous pemphigoid have not yet been performed.
Objectives
To detect, from the French Pharmacovigilance Database (FPVD), a signal of risk of bullous pemphigoid during DPP‐IV inhibitor exposure by comparative study.
Methods
All spontaneous reports of DPP‐IV inhibitor‐related bullous pemphigoid recorded in the FPVD between April 2008 and August 2014 were described. We conducted disproportionality analyses (case–noncase method) to assess the link between DPP‐IV inhibitors and bullous pemphigoid, calculating reporting odds ratios (RORs). We also compared DPP‐IV inhibitor‐induced bullous pemphigoid reports rated per million defined daily doses dispensed during the study period.
Results
Among 217 331 spontaneous adverse drug reaction reports registered in the FPVD, 1297 involved DPP‐IV inhibitors. Among these observations, 42 were bullous pemphigoid (vildagliptin, n = 31; sitagliptin, n = 10; saxagliptin, n = 1). The ROR for pooled DPP‐IV inhibitors was 67·5 95% confidence interval (CI) 47·1–96·9. Disproportionality was also observed for each DPP‐IV inhibitor: vildagliptin (ROR 225·3, 95% CI 148·9–340·9), sitagliptin (ROR 17·0, 95% CI 8·9–32·5) and saxagliptin (ROR 16·5, 95% CI 2·3–119·1). Analyses adjusted on dispensing data led to similar results.
Conclusions
These data confirm a strong signal for an increased risk of bullous pemphigoid during DPP‐IV inhibitor exposure. This adverse drug reaction is observed for each DPP‐IV inhibitor, suggesting a class effect. The signal was higher with vildagliptin than with the other DPP‐IV inhibitors.
What's already known about this topic?
Implication of dipeptidyl peptidase (DPP)‐IV inhibitors in bullous pemphigoid occurrence has been suggested in several case reports.
What does this study add?
There is a significant signal for an increased risk of bullous pemphigoid during DPP‐IV inhibitor exposure.
This signal is outlined for each DPP‐IV inhibitor, suggesting a class effect.
The signal of risk of bullous pemphigoid is higher with vildagliptin than with other DPP‐IV inhibitors.
New insights into immune thrombocytopenia (ITP) epidemiology in adult patients highlight three main outcomes of morbidity and mortality: bleeding, infection and thrombosis. This review depicts ...current evidence about incidence and risk factors of bleeding, infection and thrombosis as well as predictors of chronicity, and shows how this assessment impacts the choice of ITP second-line treatment at the individual-level basis.
Essentials
Risk factors of bleeding in adult immune thrombocytopenia are not known.
This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset.
Platelet count ...thresholds associated with bleeding were < 20 × 109 L−1 and < 10 × 109 L−1.
Exposure to anticoagulants was a major risk factor of severe bleeding.
Summary
Background
The aim of this cross‐sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds.
Methods
We selected all newly diagnosed ITP adults included in the Cytopénies Auto‐immunes Registre Midi‐PyrénéEN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models.
Results
Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 109 L−1. In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 109 L−1 versus ≥ 20 × 109 L−1, odds ratio OR 48.2, 95% confidence interval CI 20.0–116.3; between 10 × 109 L−1 and 19 × 109 L−1 versus ≥ 20 × 109 L−1, OR 5.2, 95% CI 2.3–11.6), female sex (OR 2.6, 95% CI 1.3–5.0), and exposure to non‐steroidal anti‐inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1–20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3–14.1).
Conclusions
Platelet counts of < 20 × 109 L−1 and < 10 × 109 L−1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding.
Propensity scores have been proposed in the early 1980s, and are increasingly used in epidemiology since the 2000s. They are is used to minimize the selection bias in observational studies, leading ...to a comparability between the exposure groups close to that observed in randomized trials. However, they have important limitations. Besides, new statistical techniques to improve the propensity score performances are more and more complex, while the build and the use of propensity score require a strict methodology to avoid bias, imprecision and non-reproducibility. This overview, designed for clinicians, is aimed at describing the advantages, techniques of use and limitations of propensity scores. A reading grid is provided in order to help interpreting studies using propensity scores.
Essentials
The risk factors for infection in immune thrombocytopenia are not well known.
We conducted a national pharmacoepidemiological study.
Pulmonary disease, corticosteroids and rituximab were ...the main risk factors for infections.
Pneumococcal and influenza vaccines were protective against infections.
Summary
Introduction
Risk factors for infection and protective effect of vaccines in immune thrombocytopenia (ITP) patients in the era of rituximab therapy are unknown.
Objectives
To assess the risk factors for serious and non‐serious infections (respectively, SIs and NSIs) in non‐splenectomized adults treated for persistent or chronic primary ITP, including the effect of pneumococcal and influenza vaccines.
Patients/Methods
The population was the 2009–2012 FAITH cohort (n = 1805), which is the cohort of all incident (newly diagnosed) primary ITP adults treated > 3 months in France built into the national health insurance database (SNIIRAM). SIs were hospitalizations with any infection as the primary diagnosis code. NSIs were identified using out‐of‐hospital antibiotic dispensing. Cox models were performed.
Results
Incidence rates were 6.3/100 patient‐years (95% confidence interval CI, 5.4–7.4) for SIs (lower respiratory tract in 42.8% of the cases) and 100.5/100 patient‐years (95% CI, 95.0–106.3) for NSIs. In multivariate analyses, increasing age and chronic pulmonary disease were associated with both SI and NSI occurrence. The hazard ratios (HRs) for corticosteroids and rituximab were, respectively, 3.83 (95% CI, 2.76–5.31) and 2.60 (95% CI, 1.67–4.03) for SIs and 2.46 (95% CI, 2.19–2.76) and 1.49 (95% CI, 1.28–1.74) for NSIs. Pneumococcal vaccine showed a protective effect for both SIs and NSIs (0.38 95% CI, 0.20–0.73 and 0.52 95% CI, 0.43–0.65, respectively), as did influenza vaccine (0.42 95% CI, 0.27–0.64 and 0.49 95% CI, 0.41–0.59, respectively).
Conclusions
Chronic pulmonary disease, corticosteroids and rituximab are the main risk factors for infections, whereas pneumococcal and influenza vaccines are protective against SIs and NSIs.
New insights into immune thrombocytopenia (ITP) epidemiology in adult patients highlight three main outcomes of morbidity and mortality: bleeding, infection and thrombosis. This review depicts ...current evidence about incidence and risk factors of bleeding, infection and thrombosis as well as predictors of chronicity, and shows how this assessment impacts the choice of ITP second-line treatment at the individual-level basis.
Les avancées récentes en épidémiologie du purpura thrombopénique immunologique (PTI) de l'adulte ont identifié trois risques de morbidité principaux : le saignement, l'infection et la thrombose. Cette mise au point décrit les données de la littérature sur l'incidence et les facteurs de risque de ces trois risques ainsi que les facteurs prédictifs de passage à la chronicité, et montre en quoi l'évaluation de ces éléments chez un patient donné impacte le choix du traitement de seconde ligne.
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