Trajectories of Controller Therapy Use Before and After Asthma-Related Hospitalization in Children and Adults: Population-Based Retrospective Cohort Study.

BACKGROUND: Inappropriate use of inhaled corticosteroids (ICSs) for asthma impairs control and may cause exacerbation, including asthma-related hospitalization (ARH). In prospective studies, ICS use peaked around ARH, but information on routine care use is limited. Since ARH is a major outcome, controller therapy use in routine care before and after ARH should be documented. OBJECTIVE: This study aimed to distinguish ICS use typologies (trajectories) before and after ARH, and assess their relationships with sociodemographic, disease, and health care characteristics. METHODS: A retrospective cohort study was performed using a 1% random sample of the French claims database. All patients hospitalized for asthma between January 01, 2013, and December 31, 2015, were classified as either children (aged 1-10 years) or teens/adults (aged ≥11 years). Health care resource use was assessed between 24 and 12 months before ARH. ICS use was computed with the Continuous Measures of Medication Acquisition-7 (CMA7) for the 4 quarters before and after ARH. Initially, the overall impact of hospitalization on the CMA7 value was studied using a segmented regression analysis in both children and teens/adults. Then, group-based trajectory modeling differentiated the groups with similar ICS use. We tested different models having 2 to 5 distinct trajectory groups before selecting the most appropriate trajectory form. We finally selected the model with the lowest Bayesian Information Criterion, the highest proportion of patients in each group, and the maximum estimated probability of assignment to a specific group. RESULTS: Overall, 863 patients were included in the final study cohort, of which 447 (51.8%) were children and 416 (48.2%) were teens/adults. In children, the average CMA7 value was 12.6% at the start of the observation period, and there was no significant quarter-to-quarter change in the value (P=.14) before hospitalization. Immediately after hospitalization, the average CMA7 value rose by 34.9% (P=.001), before a significant decrease (P=.01) of 7.0% per quarter. In teens/adults, the average CMA7 value was 31.0% at the start, and there was no significant quarter-to-quarter change in the value (P=.08) before hospitalization. Immediately after hospitalization, the average CMA7 value rose by 26.9% (P=.002), before a significant decrease (P=.01) of 7.0% per quarter. We identified 3 and 5 trajectories before ARH in children and adults, respectively, and 5 after ARH for both groups. Trajectories were related to sociodemographic characteristics (particularly, markers of social deprivation) and to potentially inappropriate health care, such as medical management and choice of therapy. CONCLUSIONS: Although ARH had an overall positive impact on ICS use trajectories, the effect was often transient, and patient behaviors were heterogeneous. Along with overall trends, distinct trajectories were identified, which were related to specific patients and health care characteristics. Our data reinforce the evidence that inappropriate use of ICS paves the way for ARH.

Healthcare resource use and associated costs in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis.

BACKGROUND: Real-world data regarding health-care resource use (HCRU) and costs of idiopathic pulmonary fibrosis (IPF) are scarce. In France, at the time of the study, pirfenidone and nintedanib were reimbursed for documented IPF only, with similar reimbursement criteria with regard to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in a multidisciplinary setting. The objective of this study was to evaluate costs related to HCRU in patients newly treated with pirfenidone or nintedanib in 2015-2016, in France, using the exhaustive claims data of the French National Health System. METHODS: Patients aged <50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. HCRU-related costs up to 31 December 2017 were compared using generalized linear models adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period. RESULTS: During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical visits prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with higher costs for medications (1.2; 95% CI, 1.1-1.3) and medical visits (1.3; 95% CI, 1.2-1.4), as well as a higher global cost (1.1; 95% CI, 1.0-1.2). The costs of medical procedures, hospitalizations and indirect HCRU did not statistically differ between the two cohorts. CONCLUSIONS: This observational study identified potential differences in HCRU-related costs under newly prescribed antifibrotic drugs, deserving further explorations.

Comparative non-persistence in the first year of treatment with oral anticoagulants in patients with atrial fibrillation: A French comprehensive nationwide study.

BACKGROUND: Direct oral anticoagulants (DOACs) were developed as an alternative to vitamin K antagonists (VKAs) and are commonly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Unlike VKAs, DOACs do not require Internal Normalized Ratio (INR) monitoring, but regular intake is as important for effective anticoagulation. OBJECTIVES: This study examined treatment persistence among patients receiving oral anticoagulants (OACs) for NVAF. METHODS: Within the French healthcare claims database (SNDS), we assessed and compared the rates of non-persistence (≥ 30-day treatment gap) among patients with NVAF initiating an OAC between January 2014 and December 2016. The time-to-event of non-persistence was computed and plotted using a cumulative incidence function accounting for the competing risk of mortality. After adjusting on confounding factors, the risk for non-persistence was compared between apixaban and each other OACs using a Cox proportional hazard model, or Fine and Gray models. RESULTS: In a cohort of 321,501 OAC-naive patients with NVAF, the cumulative incidence of non-persistence at 12 months considering competing risk was 44.3%, 31.0%, 41.3% and 46.8% for VKAs, apixaban, rivaroxaban and dabigatran, respectively. Median therapy duration before non-persistence ranged between 70 and 121 days. Non-persistence was lower with apixaban compared with VKAs (HR=0.63, 95%CI=[0.62-0.64]), rivaroxaban (HR=0.71, 95%CI=[0.70-0.73]), and dabigatran (HR=0.60, 95%CI=[0.59-0.62]). CONCLUSIONS: In this nationwide observational study, non-persistence rates of oral anticoagulant treatment were high in patients treated for NVAF. Apixaban-treated patients seem to experience lowest discontinuation rates 12 months after treatment initiation compared to patients treated with any other OAC.

Differences in severe exacerbations rates and healthcare utilisation in COPD populations in the UK and France.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in Europe; however, it is important to understand how clinical practice patterns differ between countries and how this might relate to disease outcomes, to identify ways of improving local disease management. We aimed to describe and compare the management of patients with COPD in the UK and France between 2008 and 2017. METHODS: We used data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics in the UK and the Echantillon Généraliste des Bénéficiaire in France to identify patients with COPD each year between 2008 and 2017. We compared patient characteristics, all-cause mortality and COPD exacerbations each year between 2008 and 2017 for patients in the UK and France separately. Health care utilisation and COPD exacerbations in 2017 were compared between France and the UK using t-tests and χ2 tests. RESULTS: Patients with COPD were similar in gender and comorbidities in both countries. Incidence of COPD exacerbations remained stable in the UK and France between 2007 and 2017. In 2017, the proportion of all-cause and COPD-related hospitalisations was greater in the UK than in France (43.9% vs 32.8% and 8.3% vs 4.9%, respectively; p<0.001) as was the proportion of patients visiting accident and emergency (A&E) (39.8% vs 16.2%, respectively; p<0.001). In addition, the mean length of stay in hospital for COPD-related causes was shorter in the UK than in France (6.2 days (SD 8.4) vs 10.5 days (SD 9.1), respectively; p<0.001). DISCUSSION: Overall, UK patients were more likely to go to A&E, be hospitalised for COPD-related causes and stay in hospital for fewer days after being admitted for COPD-related reasons compared with patients in France, illustrating a difference in health-seeking behaviours and access to healthcare.

Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis.

BACKGROUND: Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion. RESEARCH QUESTION: The data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015-2016. STUDY DESIGN AND METHODS: Patients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period. RESULTS: During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3-2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0-1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6-0.9). INTERPRETATION: This observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

Mortality and Respiratory-Related Hospitalizations in Idiopathic Pulmonary Fibrosis Not Treated With Antifibrotics.

Background: Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. The claims data from the French National Health System (SNDS) were used to describe outcomes in patients diagnosed with IPF in 2015-2016 but who did not receive antifibrotic therapies. Method: Patients aged <50 years were excluded, as were patients with pulmonary fibrosis other than IPF, patients who had previously received a lung transplant, and those who had received antifibrotic therapies at any time between 2010 and 2016. Patients were followed-up until their last health record, lung transplantation, initiation of antifibrotic therapies, death, or the end of the study period (31 December 2017), whichever occurred first. Results: A total of 5,360 patients (43.2%) not treated with antifibrotic therapies were included. The mean age was 75.5 years, and 57.9% were males. In the year before inclusion, 47.3% of patients had a Charlson score ≥5. During follow-up, 41.2% of patients died. The unadjusted incidence rate was 29.9 per 100 person-years (95%CI = [28.7-31.2]), and the cumulative incidence of death at 3 years was 50.2% (95% CI = [48.3-52.1%]). In the study population, 35.3% of patients experienced an acute respiratory-related hospitalization. The unadjusted incidence rate was 32.1 per 100 person-years (95%CI = [30.6-33.5]) and the cumulative incidence of the event at 3 years was 41.5% (95% CI = [39.7-43.2%]). Interpretation: This observational study showed that, if untreated with antifibrotics, IPF is associated with a 50% all-cause mortality at 3 years. These figures can serve as a historical control of the natural course of the disease.

10-Year Comparative Follow-up of Familial versus Multifactorial Chylomicronemia Syndromes.

CONTEXT: The relative incidence of acute pancreatitis, ischemic cardiovascular disease, and diabetes in hyperchylomicronemic patients exhibiting familial chylomicronemia syndrome (FCS) or multifactorial chylomicronemia syndrome (MCS) is unknown. OBJECTIVE: The objective was to study the occurrence of these events in FCS and MCS patients compared with the general population. METHODS: Twenty-nine FCS and 124 MCS patients, with genetic diagnosis, in 4 lipid clinics were matched with 413 controls. Individual hospital data linked to the national claims database were collected between 2006 and 2016. The occurrence of complications was retrospectively assessed before follow-up and during a median follow-up time of 9.8 years, for 1500 patient years of follow-up. RESULTS: Patients with FCS were younger than those with MCS (34.3 ±â€…13.6 vs 45.2 ±â€…12.6 years, P < 0.01). During the study period, 58.6% of the FCS patients versus 19.4% of the MCS patients had at least 1 episode of acute hypertriglyceridemic pancreatitis (AHP) (hazard ratio [HR] = 3.6; P < 0.01). Conversely, the ischemic risk was lower in FCS than in MCS (HR = 0.3; P = 0.05). The risk of venous thrombosis was similar in both groups. The incidence of diabetes was high in both groups compared with matched controls (odds ratio [OR] = 22.8; P < 0.01 in FCS and OR = 30.3; P < 0.01 in MCS). CONCLUSION: The incidence of AHP was much higher in FCS than in MCS patients, whereas the incidence of ischemic cardiovascular events was found to be increased in MCS versus FCS patients and a representative matched control group. Differences in both triglyceride-rich lipoproteins metabolism and comorbidities in MCS versus FCS drive the occurrence of different patterns of complications.

Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study.

BACKGROUND AND PURPOSE: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. METHODS: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. RESULTS: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. CONCLUSIONS: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

Characteristics and management of giant cell arteritis in France: a study based on national health insurance claims data.

OBJECTIVE: Few data are available on the epidemiology and management of GCA in real life. We aimed to address this situation by using health insurance claims data for France. METHODS: This retrospective study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1% representative sample of the French national health insurance system. The EGB contains anonymous data on long-term disease status, hospitalizations and reimbursement claims for 752 717 people. Data were collected between 2007 and 2015. The index date was defined as the date of the first occurrence of a GCA code. Demographics, comorbidities, diagnostic tests and therapies were analysed. Annual incidence rates were calculated, and incident and overall GCA cases were studied. RESULTS: We identified 241 patients with GCA. The annual incidence was 7-10/100 000 people ⩾50 years old. Among the 117 patients with incident GCA, 74.4% were females, with mean age 77.6 years and mean follow-up 2.2 years. After the index date, 51.3% underwent temporal artery biopsy and 29.1% high-resolution Doppler ultrasonography. Among the whole cohort, 84.3% used only glucocorticoids. The most-prescribed glucocorticoid-sparing agent was methotrexate (12.0%). CONCLUSION: The incidence of GCA in France is 7-10/100 000 people ⩾ 50 years old. Adjunct agents, mainly methotrexate, are given to only a few patients. The use of temporal artery biopsy in only half of the patients might reflect a shift toward the use of imaging techniques to diagnose GCA.

Dual versus triple therapy in patients hospitalized for COPD in France: a claims data study.

Purposes: Following a hospitalization for COPD, dual and triple therapies were compared in terms of persistence and relations with outcomes (exacerbations, health care resource use and costs). Methods: This was a historical observational database study. All patients aged ≥45 hospitalized for COPD between 2007 and 2015 were identified in a 1/97th random sample of French claims data. Patients receiving dual therapy within 60 days after hospitalization were compared to patients receiving triple therapy, after propensity score matching on disease severity. Results: Of the 3,089 patients hospitalized for COPD, 1,538 (49.8%) received either dual or triple therapy in the 2 months following inclusion, and 1,500 (48.6%) had at least 30 days of follow-up available; 846 (27.4%) received dual therapy, and 654 (21.2%) received triple therapy. After matching, the number of exacerbations was 2.4 per year in the dual vs 2.3 in the triple group (p=0.45). Among newly treated patients (n=206), persistence at 12 months was similar in the dual and triple groups (48% vs 41%, respectively, p=0.37). As compared to patients on dual therapy, more patients on triple therapy received oral corticosteroids (49.1 vs 40.4%, p=0.003) or were hospitalized for any reason (67% vs 55.8%, p=0.0001) or for COPD (35.3 vs 25.1%, p=0.0002) during follow-up. Cost of care was higher for patients on triple than for those on dual therapy (€11,877.1 vs €9,825.1, p=0.01). Conclusion: Following hospitalizations for COPD, patients on dual and triple therapy experienced recurrent exacerbations, limited adherence to therapies and high cost of care. Patients on triple therapy appeared more severe than those on dual therapy, as reflected by exacerbations and health care resource use.

Epidemiology, treatment patterns and outcomes in patients with coronary or lower extremity artery disease in France.

BACKGROUND: There is a dearth of updated epidemiological data on the prevalence and annual incidence of coronary artery disease (CAD) and lower extremity artery disease (LEAD) in Western countries. AIMS: To describe the incidence and prevalence of CAD and LEAD, associated medication patterns and long-term outcomes in France. METHODS: This was a retrospective cohort study using French claims data from a representative sample of the French general population. Any hospitalization or long-term disease status for CAD or LEAD between January 2010 and December 2016 was collected to identify incident cases. RESULTS: Of the 763,338patients screened in the study period, 8559 incident cases of CAD and 4399 of LEAD were identified, with an overall mean follow-up of 2.9±2.0years. The incidence of CAD, LEAD and CAD or LEAD remained stable over the years, and in 2016 were at 33.5 per 10,000person-years, 15.1per 10,000person-years and 42.5 per 10,000person-years, respectively. The prevalence of CAD increased from 3.1% in 2010 to 4.2% in 2016, and LEAD from 1.6% to 2.4%. Most patients received guideline-recommended medication with antithrombotic drugs and lipid-lowering drugs following the index event. However, most of the medications initiated were subsequently discontinued during follow-up. Incident CAD or LEAD was associated with considerable morbidity-particularly an incidence of all-cause hospitalization of 7976.9 per 10,000person-years-and all-cause mortality, with an incidence of 542.8 per 10,000person-years. CONCLUSION: In recent years, the prevalence of CAD or LEAD has increased progressively, resulting in considerable morbidity and mortality.

Changes in Persistent Asthma Care and Outcomes From 2006 to 2016 in France.

BACKGROUND: Changes in asthma care need to be documented at arrival of biotherapies. OBJECTIVES: To characterize changes in asthma care and outcomes in patients with persistent asthma. METHODS: Repeated transversal analyses were conducted on a historical cohort using the French national claims data over 10 years. Patients aged 18 to 40 years with either 1 or more (any-use population) or 4 or more (high-use population) yearly dispensings of controller therapy were selected. Clinical and demographic features were characterized, and comparisons were made between 2006 and 2016 to assess temporal changes in asthma therapy, health care resource utilization, and outcomes. RESULTS: In 2016, prevalent use of controller therapy was 5.2% (any-use population) and 0.8% (high-use population) of the population aged 18 to 40 years. In the any-use population, the use of long-acting ß2-agonists in monotherapy, and inhaled corticosteroids decreased (1.7% and 40.3% in 2016, respectively), whereas the use of fixed-dose combinations increased (56.4%). In both populations, visits to respiratory or hospital physicians and pulmonary function testing increased with time, in parallel to a decreasing number of general practitioner visits; in addition, oral corticosteroid use and incidence of emergency room visits increased. However, asthma hospitalizations and mortality remained low in both populations. CONCLUSIONS: Changes in persistent asthma care included replacement of inhaled corticosteroids by fixed-dose combinations, decreased use of long-acting ß2-agonists as a monotherapy, and increased involvement of secondary care physicians. In parallel, despite low figures for hospital admissions and mortality, overall use of oral corticosteroids and incidence of emergency room visits have increased over the last decade.

Asthma exacerbations and socio-economic status in French adults with persistent asthma: A prospective cohort study.

INTRODUCTION: Adults disadvantaged by poor socio-economic status (SES) are more severely affected by asthma compared to those with better SES. We aimed to determine whether the frequency of asthma exacerbations (AEx), as well as aspects related to AEx management, differed based on SES in patients treated with daily treatments. METHODS: This study, part of the prospective observational cohort ASTRO-LAB, included French adult patients with persistent asthma. Patients were considered as low SES if they benefited from publicly funded special health insurance and/or were perceived as low SES by their general practitioner. AEx was defined as at least one of the following: asthma-related oral corticosteroid course, medical contact, hospitalization, and death. We examined associations between SES and AEx frequency, perceived triggering factors and type of medical contact after AEx. RESULTS: In our sample of 255 patients, 11.40% were considered as low SES. Patients with low SES did not report significantly more AEx than medium/high SES patients during one-year follow-up (0.79 versus 0.55, p = 0.38). The type of medical contact during AEx differed significantly between the two groups (p = 0.03): patients with medium/high SES consulted their general practitioner more frequently (OR = 2.23, 95% CI = 0.91-5.50, p = 0.08) and were less likely to visit an emergency department or be hospitalized (OR = 0.27, 95% CI = 0.09-0.84, p = 0.02). CONCLUSIONS: AEx frequency did not differ significantly between low and medium/high SES patients, but differences were found in the management of AEx. Studies are needed to better understand the relation between precariousness and management of asthma.