Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

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.

Impact of persistence with tumour necrosis factor inhibitors on healthcare resource utilization and costs in chronic inflammatory joint diseases.

AIM: To assess persistence with subcutaneous (SC) tumour necrosis factor (TNF) inhibitors as well as the impact of persistence on healthcare resource utilization (HCRU) and costs in patients with chronic inflammatory joint diseases. METHODS: In this cohort study using population-based French claims data (from 2011 to 2014), we measured persistence with SC TNF inhibitors within 12 months (M0-12) following treatment initiation in treatment-naïve and treatment-experienced users (divided into three cohorts: rheumatoid arthritis [RA], ankylosing spondylitis [AS] and psoriatic arthritis [PsA]). Persistent patients were propensity score matched to nonpersistent patients at M12. The impact of persistence status on HCRU and costs was assessed during M12-24. RESULTS: Of treatment-naïve (n = 3,804) and treatment-experienced (n = 2,279) users, only 56.1% and 46.8% were persistent at M12, respectively. Nonpersistent patients had more outpatient visits, computerized tomography scans, spine or joint magnetic resonance imaging procedures and disease-related hospitalizations, while persistent patients had more rheumatologist visits. Nonpersistent patients had lower drug costs but higher nondrug-related healthcare and hospitalization costs than persistent patients. In AS and PsA, overall healthcare costs were similar in persistent and nonpersistent patients. In RA, overall healthcare costs were lower in persistent patients (15,753€ vs 17,590€ in treatment-naïve and 17,622€ vs 21,177€ in treatment-experienced). CONCLUSION: Persistence with SC TNF inhibitors within first 12 months following treatment initiation was low in both treatment-naïve and treatment-experienced patients. Differences were observed in distribution of costs between persistent and nonpersistent patients, showing that nonpersistence with SC TNF inhibitors can lead to increased HCRU and higher costs.

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.

Effects of short- and long-acting beta-agonists on asthma exacerbations: a prospective cohort.

BACKGROUND: In asthma, short- and long-acting ß-agonists (SABAs and LABAs) should be used together with inhaled corticosteroids (ICS), and regular use is inappropriate. OBJECTIVE: To assess the relationship between patterns of use of therapy and asthma exacerbations (AEx). METHODS: Patients with asthma (6-40 years) were enrolled in France and the United Kingdom. Prescribing data, computer-assisted telephone interviews (CATIs), and text messages assessed medication use and AEx over a maximum period of 24 months. Generalized linear mixed models provided AEx risks associated with therapy. RESULTS: Among the 908 patients (median age: 20.0 years, 46.6% women, 24.5% children) answering a total of 4248 CATIs over 486 (±235) days, regular (ie, daily) use was more frequent for single LABAs and fixed dose combinations (FDCs) than for single ICS (75.6%, 70.1%, and 65.4% of investigated periods of use, respectively). Regular (ie, daily or almost daily) SABA use was observed for 21.1% of periods of use. Altogether, 265 patients (29.2%) experienced 1 or more AEx. The ORs for AEx risk related to regular vs no use of FDCs, single ICS, and single LABAs were 0.98 (95% CI = [0.73-1.33]), 0.90 (95% CI = [0.61-1.33]), and 1.29 (95% CI = [0.76-2.17]), respectively, after adjustment for cotherapy, sociodemographic, and disease characteristics. The OR was 2.09 (95% CI = [1.36-3.21]) in regular SABA users. CONCLUSION: Inhaled corticosteroids and FDCs were often used intermittently, whereas SABAs and LABAs could be used regularly, and exacerbations were frequent. Compared with non-users, the risk of exacerbation increased moderately under regular use of single LABAs, whereas it doubled, significantly, in regular SABA users, likely in relationship with poor overall asthma control.

[Early adherence to anti-glaucoma therapy: An observational study]. / Étude observationnelle sur l'adhésion précoce aux traitements hypotonisants anti-glaucomateux.

OBJECTIVES: Glaucoma is a major cause of blindness, preventable by a regular therapy. Thus, a good knowledge of patients' adherence to preventive therapy is critical to improve disease management. Early persistence to first-line glaucoma therapy is poorly documented in France. We verified to what extent first-line glaucoma therapy was interrupted within the 12 months following initiation and how this interruption varied with patients' characteristics and drug classes. METHODS: Patients newly-treated with chronic glaucoma therapy (prostaglandins, beta-blockers alone or combined with another therapy, and topical carbonic anhydrase inhibitors) between 2005 and 2008 were identified in the French National Claims data (1/97th random sample). Twelve-month persistence was defined by the presence of the first-line drug class (≥1dispensation) between the 12th and 24th months following initiation. Twelve-month persistence was compared between patients according to the first-line drug classes and baseline characteristics. Proportion of days covered (12 months) and number of quarters with initiated drug class (24 months) were also studied. RESULTS: Among 5331 patients initiated with chronic glaucoma therapy in monotherapy (63% aged ≥60 years old, 57% females), initiated therapy mainly consisted of prostaglandins (43%) and beta-blockers alone (32%). Only 45% of the patients were persistent to first-line therapy 12 months after initiation. Salient differences in persistence rates appeared between drug classes (P<0.0001): from 59% with prostaglandins to 26% for topical carbonic anhydrase inhibitors. Better results also appeared for prostaglandins with other dimensions of adherence. Non-persistent patients were more likely younger than 40, or conversely aged≥80 (P<0.0001). They were also more likely to necessitate social assistance for therapy (P=0.0007). No salient difference appeared as to gender. CONCLUSIONS: Our findings confirm the low early persistence of first-line therapy, despite better results for prostaglandins. Education of patients and identification of barriers to adherence could contribute to improve quality of care.

Effectiveness of Montelukast on asthma control in infants: methodology of a French claims data study.

BACKGROUND: This pilot study, conducted on a 1/97th representative sample of French claims data, prepared a project to assess the effectiveness of Montelukast (MTL-4) as add-on therapy for asthma in infants (6-24 months) compared to inhaled corticosteroids (ICS), based on real-world data. Due to the very recent opening of French claims data for effectiveness research, and the complex structure of this data source, we first tested the feasibility of identifying infants with asthma and outcome criteria, and the ability to perform relevant comparisons. METHODS: We identified a cohort of infants with uncontrolled asthma and receiving ≥2 consecutive dispensations of any respiratory drug (R03 ATC classification) during a 6-month period. Uncontrolled asthma was identified either from exacerbations or from markers of acute loss of asthma control; date of occurrence of an event (exacerbation and/or acute loss of asthma control) was defined as index date. The study groups comprised infants receiving MTL-4 +/- ICS (MTL-4 group) or ICS without MTL-4 (ICS group) at index date. These two groups were matched on gender, age, quarter of index date, therapy before index date, past asthma-related hospitalization (ever), and were followed for 6 months. The outcome was the rate of infants with uncontrolled asthma, defined as above. RESULTS: This pilot cohort study included 1,149 infants with asthma (mean age 14.1 months, 64% boys). Of these, 51 and 768 were assigned to the MTL-4 and ICS groups, respectively. Uncontrolled asthma occurred in 78.8% and 78.4% of infants in these groups, respectively (oral corticosteroids were dispensed to 49% and 61%, respectively). Assessment of uncontrolled asthma, exposure to MTL-4 and ICS, and occurrence of outcomes were achieved. For the development of matching criteria, we defined a new marker of severity (therapeutic typologies). CONCLUSION: These data support the feasibility of the final project, to be conducted on claims data from the whole French population. We also showed that, with appropriate methodology and by using valid criteria, French claims data are an adequate resource for conducting comparative effectiveness studies in pediatric asthma. Finally, the algorithm used to identify infants with asthma could be applied to other studies using claims data.

Prescribed therapy for asthma: therapeutic ratios and outcomes.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy. The ICS-to-total-asthma-medication ratios, calculated from claims data, indicate potentially risky disease management in asthma. Our aim was to assess the utility of ICS-to-total-asthma-medication ratios from primary care electronic medical records (EMRs) in detecting patients at risk of asthma exacerbation, as approached by prescription of oral corticosteroids and/or antibiotics. METHODS: Retrospective cohort studies were identified, using the Health Improvement Network general practice database (THIN, United Kingdom) and the Cegedim Longitudinal Patient Data (France). We selected asthma patients aged 16-40 years, with ≥ 4 prescriptions for asthma medications in 2007 and ≥ 1 prescription in 2008. For each country, three groups were defined according to ratio value in 2008: 0% (non-ICS users), <50% (low-ICS-ratio group) and ≥ 50% (high-ICS-ratio group). Outcomes were marker of asthma exacerbations: systemic corticosteroids and antibiotics. They were compared between groups in each country. RESULTS: Among 38,637 British and 4,587 French patients, higher numbers of prescriptions per patient of systemic corticosteroids, antibiotics and total asthma medications were observed in the low-ICS-ratio groups compared to other groups (p < 0.0001 for each outcome in both countries). Likewise, low-ICS-ratio patients had more medical contacts (p < 0.0001 in both countries), suggesting poorly controlled asthma. ICS-treated patients had lower risks of receiving systemic corticosteroids in 2008 in the high-ICS-ratio group, compared to the low-ICS-ratio group: RR = 0.54, 95%CI = [0.50-0.57] and RR = 0.78, 95%CI = [0.67-0.91] in the UK and France, respectively. CONCLUSIONS: Patients with high ICS-to-total-asthma-medication ratios presented fewer asthma-related outcomes. The low ICS-to-total-asthma-medication ratio calculated with EMRs data reflects insufficient prescribing of ICS relative to all asthma medications, which may lead to deteriorated asthma control.

[Factors associated with drug prescription in general practice: a multicenter cross-sectional study]. / Facteurs associés à la prescription médicamenteuse en médecine générale : une étude transversale multicentrique.

OBJECTIVE: Iatrogenic, environmental and economic consequences of drug prescription are public health issues. This study was designed to identify physician, patient and consultation characteristics that influence drug prescription in general practice. METHODS: A national multicentre cross-sectional study was conducted in general practice from December 2011 to Apri/2012. Bivariate analyses were performed, followed by multivariate analyses based on a mixed model. RESULTS: At least one drug was prescribed in 16,626 (80.7%) of 20,600 consultations conducted by 128 practitioner. Apart from the number of health problems managed (OR= 10.6 [8.8; 13.0] if :2 4), independent patient-related factors were female gender (OR= 1.1 [1.0; 1.2]), extreme ages (OR= 1.3 [1.1; 1.5]younger than 4 years, OR= 1.5 [1.3; 1.8] from 5 to 14 years, and OR= 1.3 {1.2; 1.5] older than 60 years vs. between 15 to 29 years), new patients (OR= 0.8 {0. 7; 0.9]), work accident or occupational disease (OR= 0.3 {0.3; 0.4]). For the physician, drug prescription was linked to visits by pharmaceutical representatives (OR = 1.6 [1.2; 2.0] if :2 5 times a week) but not to visits by Public Health Insurance delegates or signature of the contract designed to improve individual practices (CAP/). CONCLUSIONS: Independently of health problems, patient and physician characteristics, including visits by pharmaceutical representatives, influence drug prescription.

Relative exposure to controller therapy and asthma exacerbations: a validation study in community pharmacies.

PURPOSE: "Controllers-to-total asthma drug" ratios computed from claims data identify asthmatics at risk of exacerbations. Direct link of ratios to data obtained from patients, such as control and recent outcomes, would facilitate their interpretation. We studied the relationship between R1 ratio (inhaled corticosteroids (ICS)/total anti-asthma drug ratio) and the Asthma Control Test. Comparisons were also conducted for secondary outcomes (asthma-related hospital contacts, monthly medical contacts, use of oral corticosteroids, and perception of disease burden). Results with R1 ratio were compared with those obtained with a second ratio, "ICS-plus-leukotriene receptor antagonist/total asthma drug" (R2 = ICS + leukotriene receptor antagonist/total anti-asthma drugs). METHODS: A survey was conducted in community pharmacies. Patients visiting with a prescription of anti-asthma drug and ≥12 months of drug dispensing recorded in the pharmacy were consecutively recruited. Dispensing data were linked to patient-reported outcomes. Asthma control and secondary outcomes were compared for both ratios between low-controller-ratio (R < 50%) and high-controller-ratio groups (R ≥ 50%), after excluding null values. RESULTS: Of the 919 eligible patients (mean age 37 years, 55% women), 90.2% and 92.4% had non-null values for R1 and R2, respectively. Compared with the low-controller-ratio groups, adjusted risks of being uncontrolled were significantly lower in the high-controller-ratio groups (RR = 0.64, 95%CI [0.54, 0.77] and RR = 0.57, 95%CI [0.47, 0.70], for R1 and R2 ratios, respectively). Likewise, fewer patients with secondary outcomes were observed in the high-controller-ratio groups, for both ratios. CONCLUSION: Asthma was better controlled among patients with high controller ratios, along with fewer asthma-related outcomes, for both R1 and R2 ratios. This confirms the utility of asthma/drug ratios in identifying patients at risk of exacerbations, notably in claims data.

Health Care Resource Use and Total Mortality After Hospital Admission for Severe COVID-19 Infections During the Initial Pandemic Wave in France: Descriptive Study.

BACKGROUND: Little is known about post-hospital health care resource use (HRU) of patients admitted for severe COVID-19, specifically for the care of patients with postacute COVID-19 syndrome (PACS). OBJECTIVE: A list of HRU domains and items potentially related to PACS was defined, and potential PACS-related HRU (PPRH) was compared between the pre- and post-COVID-19 periods, to identify new outpatient care likely related to PACS. METHODS: A retrospective cohort study was conducted with the French National Health System claims data (SNDS). All patients hospitalized for COVID-19 between February 1, 2020, and June 30, 2020 were described and investigated for 6 months, using discharge date as index date. Patients who died during index stay or within 30 days after discharge were excluded. PPRH was assessed over the 5 months from day 31 after index date to end of follow-up, that is, for the post-COVID-19 period. For each patient, a pre-COVID-19 period was defined that covered the same calendar time in 2019, and pre-COVID-19 PPRH was assessed. Post- or pre- ratios (PP ratios) of the percentage of users were computed with their 95% CIs, and PP ratios>1.2 were considered as "major HRU change." RESULTS: The final study population included 68,822 patients (median age 64.8 years, 47% women, median follow-up duration 179.3 days). Altogether, 23% of the patients admitted due to severe COVID-19 died during the hospital stay or within the 6 months following discharge. A total of 8 HRU domains were selected to study PPRH: medical visits, technical procedures, dispensed medications, biological analyses, oxygen therapy, rehabilitation, rehospitalizations, and nurse visits. PPRs showed novel outpatient care in all domains and in most items, without specificity, with the highest ratios observed for the care of thoracic conditions. CONCLUSIONS: Patients hospitalized for severe COVID-19 during the initial pandemic wave had high morbi-mortality. The analysis of HRU domains and items most likely to be related to PACS showed that new care was commonly initiated after discharge but with no specificity, potentially suggesting that any impact of PACS was part of the overall high HRU of this population after hospital discharge. These purely descriptive results need to be completed with methods for controlling for confusion bias through subgroup analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05073328; https://clinicaltrials.gov/ct2/show/NCT05073328.

Health care resource utilization preceding death or lung transplantation in people with cystic fibrosis: HCRU before transplant or death in cystic fibrosis.

BACKGROUND: We studied the health care resource utilization (HCRU) and associated costs in the year preceding LT in pwCF or death without LT, and we estimated the overall cost of LT. METHODS: We performed a linkage between 2006 and 2017 data from the French CF Registry (FCFR) and the French health claims database (Système National des Données de Santé; SNDS). The HCRU and associated costs were described the year before LT or before death without LT, and two years after LT. RESULTS: Among the 7,671 patients included in the FCFR, 6,187 patients (80.7 %) were successfully matched to patients in the SNDS (males (m): 51.9 %, mean±SD age at the end of follow-up: 24.6 ± 13.6). Overall, 166 patients died without LT (m: 47.6 %, age at death: 30.4 ± 14.5) and 767 patients with primary LT (m: 48.2 %, age at transplantation: 28.0 ± 9.1) were identified. HCRU was lower among patients who died without receiving LT, with marked differences in the cost of hospital stays. The mean total cost per patient was €66,759 ± 38,249 in the year before death, €149,374 ± 62,678 in the year preceding LT, €63,919 ± 35,399 in the first year following LT, and €42,813 ± 39,967 in the second year of follow-up. CONCLUSION: Our results indicate that HCRU was two times lower in the year before death in non-transplant pwCF than in the year before LT, which may reflect inappropriate care of CF in patients who died without receiving LT. It also shows the cost associated with LT.

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.

Coverage rates for diphtheria, tetanus, poliomyelitis, and pertussis age-specific booster recommendations in France: 2018 update of the real-world cohort analysis.

The French National Immunization Program was updated in 2013 for vaccination against diphtheria, tetanus, pertussis, and poliomyelitis. Our previous findings on the evolution of age-specific booster vaccination coverage rates (VCRs) up to 2017 suggested suboptimal vaccination coverages due to the pre-2013 recommendation-residual vaccination practices. In the current analysis, we evaluated all age-specific booster VCR and distribution of age at vaccination visits in 2018. In this retrospective observational cohort study, the cumulative booster VCRs were updated at all vaccination visits up to 2018 among the people who were eligible for a booster vaccination, using a 1/97th random sample of French national healthcare reimbursement databases. The cumulative booster VCR for individuals from all age groups increased from 2017 to 2018, except for 85-years-old vaccination visit. Majority of the individuals from all age groups were vaccinated (boosted) with a vaccine containing the pertussis valence. In 2018, sharp peaks corresponding to the recommended ages for booster vaccination visits were observed for individuals aged 6, 11 to 13, 25, 45, and 65 years. Our study reiterates suboptimal coverages in France and implies the need for booster vaccination throughout life for the protection of the population.

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.

Apixaban versus other anticoagulants in patients with nonvalvular fibrillation: a comparison of all-cause and event-related costs in real-life setting in France.

OBJECTIVES: Compare costs associated with all-cause healthcare resource use (HCRU), stroke/systemic thromboembolism (STE) and major bleedings (MB) between patients with non-valvular atrial fibrillation (NVAF) initiating apixaban or other oral anticoagulants (OACs). METHODS: We performed a retrospective cohort study using the French healthcare claims database, including NVAF patients between 2014/01/01 and 2016/12/31, followed until 2016/12/31. We used 4 sub-cohorts of OAC-naive patients, respectively initiating apixaban, dabigatran, rivaroxaban or VKAs. We matched patients initiating apixaban with patients initiating each other OACs using 1:n propensity score matching. All-cause HCRU and event-related costs by OAC treatment were estimated and compared between matched patients using generalised-linear models with gamma-distribution and two-part models. RESULTS: There were 175,766 patients in the apixaban-VKA, 181,809 in the apixaban-rivaroxaban, and 42,490 in the apixaban-dabigatran matched cohorts. Patients initiating apixaban had significantly lower HCRU costs than patients initiating VKA (€1,105 vs. €1,578, p < 0.0001), dabigatran (€993 vs. €1,140, p < 0.0001) and rivaroxaban (€1,013 vs. €1,088 p < 0.0001). They have had significantly lower costs related to stroke/STE and MB than patients initiating VKA (respectively, €183 vs. €449 and €147 vs. €413; p < 0.0001), rivaroxaban (respectively, €145 vs. €197 and €129 vs. €193; p < 0.0001), and lower costs related to stroke/STE than patients initiating dabigatran (€135 vs. €192, p < 0.02). Costs related to MB were not significantly different in patients initiating apixaban and those initiating dabigatran (€119 vs. €149, p = 0.07). CONCLUSIONS: HCRU and most event-related costs were lower in patients initiating apixaban compared to other OACs. Apixaban may be cost-saving compared to VKAs, and significantly cheaper than other DOACs, although cost differences are limited.

Cocooning strategy: Pertussis vaccination coverage rate of parents with a new-born in 2016 and 2017 in France.

Background: The "cocooning" strategy was introduced in 2004 to protect infants too young to be vaccinated against pertussis, by immunizing their parents and close relatives. The study objective was to assess its implementation 12 years after its introduction by estimating the pertussis vaccination coverage rates (VCR) among parents of newborns. Materials and methods: Pertussis VCR were estimated among all women who gave birth and men who took paternity leave, in 2016 or 2017, from a 1/97th random sample of French claims data. Two distinct study periods were defined based on current recommendations for the cocooning strategy: the "common practice" and the "parental project" periods. Results: In 2016, the pertussis VCR of women having given birth and men having taken paternity leave was 47.2 and 47.1%, respectively (46.1 and 45.6% in 2017, respectively). About one quarter of vaccinations were performed during the "parental project" period, with the vaccine most frequently reimbursed during the month of childbirth for women (57.1% in 2016 and 49.4% in 2017) and before or during the month the paternity leave began for men (about 78% in both 2016 and 2017). General practitioners were the main prescribers in private practice, even during the "parental project" period. Conclusion: To optimize the protection for infants, the main objective of the cocooning strategy, pertussis immunization coverage of adults and seniors needs to be improved. Moreover, cocooning vaccination linked to a parental project needs to be performed earlier, during pregnancy (for those around the mother) or in immediate post-partum (e.g., during the maternity stay).

Treatment of Allergic Rhinitis and Asthma in Primary Care: Dispensations Do Not Align with Prescriptions.

Background: Appropriate use of effective treatments is required for satisfactory control of allergic symptoms. Coherent medical care -regular prescribing by the same Health Care Professionals- is a preliminary need. Objective: We investigated the numbers of distinct prescribers, the regularity of medical visits, and the agreement between prescriptions and associated dispensations in individual patients with perennial allergic rhinitis (PAR) and asthma. Methods: In primary care electronic health records (EHRs), a cohort of patients with PAR and asthma was identified. Individual EHRs were linked to corresponding claims recording all dispensations. Prescribing patterns were analyzed for the major treatment classes, and the dispensations linked to individual prescriptions were retrieved to compute the proportions of days covered (PDCs) for asthma and PAR therapy. Results: A total of 3654 patients were included, with 62% being female (mean age, 46.1 years). At inclusion, asthma control was not optimal in 51% of the patients and 48% had received oral corticosteroids. The mean interval between successive prescriptions varied between 93 (leukotriene receptor antagonists, LTRAs) and 103 (inhaled corticosteroids, ICS) days, and 97 (antihistamines, AHs) and 103 days (nasal corticosteroids, NCS). On average, individual prescriptions lead to 1.2, 1.5, 1.7 and 1.8 dispensations of ICS, ICS/Long-Acting Beta-Agonist (LABA) fixed-dose combinations, LABAs, and LTRAs, respectively, and to 1.3 and 1.6 dispensations of NCS and AHs, respectively. PDCs then varied between 37.8% for ICS and 58.6% for LTRAs, and between 39.7% for NCS and 50.4% for AHs. Care was nonetheless coherent, with >90% of all dispensations related to prescriptions issued by single General Practitioners (GPs). Conclusion: Despite regular healthcare visits and medication prescriptions, allergic patients only partly and selectively refilled their treatments, preferring the less effective therapy, in a context of poor control of asthma symptoms.

Temporal trends in healthcare resource use and associated costs of patients with cystic fibrosis.

BACKGROUND: Better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life expectancy of affected individuals. This study evaluated how the combination of modified demographics and changes in CF management impacted resource consumption and the cost of care. METHODS: Medical records of CF patients from 2006 to 2016 in the French CF Registry were linked to their corresponding claims data (SNDS). Medications, medical visits, procedures, hospitalisations, and indirect costs were annualized by calendar year from 2006 to 2017. RESULTS: Of the 7,671 patients included in the French CF Registry, 6,187 patients (80.7%) were linked to the SNDS (51.9% male, mean age = 24.7 years). The average cost per patient was €14,174 in 2006, €21,920 in 2011 and €44,585 in 2017. Costs associated with hospital stays increased from €3,843 per patient in 2006 to €6,741 in 2017. In 2017, the mean cost per CF patient was allocated as follows: 72% for medications (of which 51% for modulator therapies), 15% for hospital stays, 7% for medical visits, 3% for indirect costs, 2% for medical devices, 1% for outpatient medical procedures. CONCLUSION: There was a strong increase in the mean annual cost per CF patient between 2006 and 2017, mostly due to the cost of therapy after the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. The combination of an increase in the number of CF patients - particularly adult patients - and an increase in the annual cost per patient led to a substantial increase in the total cost of CF disease care for the health systems.