Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms.

BACKGROUND: The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. METHODS: We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®- Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking-OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). RESULTS: Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. DISCUSSION: There are major differences between countries in terms of rhinoconjunctivitis medication usage.

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.

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.

Does adherence to inhaled corticosteroids predict asthma-related outcomes over time? A cohort study.

Inhaled corticosteroids (ICS) adherence is important for asthma management. Current evidence on the impact of ICS adherence on outcomes is mostly based on correlational analyses of between-person data. Although it is widely acknowledged that asthma outcomes fluctuate over time, evidence on predictors of within-person change is scarce. We aimed to quantify these fluctuations and the longitudinal relationships between ICS adherence and outcomes at both between- and within-person levels.A prospective cohort of persistent asthma patients in France and the UK (n=847, age 6-40 years) provided 3756 reports over up to 2 years via computer-assisted telephone interviews and text messages on ICS adherence, asthma control, reliever medication use and exacerbations. We examined adherence-outcome relationships via longitudinal models, controlling for confounders, including severity.Considerable within-person variability was found for exacerbations (91%), asthma control (59%) and reliever use (52%); 431 (11.5%) reports signalled exacerbations and 2046 (54.5%) poor control. At between-person level, patients with higher average adherence were more likely to report asthma control (OR 1.25, 95% CI 1.06-1.47), but not asthma exacerbations (OR 0.99, 95% CI 0.87-1.12) or lower reliever use (b -0.0004, 95% CI -0.089-0.088). At within-person level, higher-than-usual adherence was associated with higher concomitant reliever use (b 0.092, 95% CI 0.053-0.131) and lower subsequent reliever use (b -0.047, 95% CI -0.005- -0.088); it was unrelated to asthma control (OR 0.93, 95% CI 0.84-1.02) or exacerbations (OR 1.04, 95% CI 0.94-1.16).Patients maintaining high ICS adherence over time have better asthma control. Temporarily increasing ICS adherence tends to be simultaneous to higher reliever use and reduces reliever use later on. Causes of within-person variation in outcomes require more investigation.

EuroQol (EQ-5D-5L) Validity in Assessing the Quality of Life in Adults With Asthma: Cross-Sectional Study.

BACKGROUND: The EuroQol-5 Dimension (EQ-5D), developed in 1990, is a most widely used generic tool to measure the health-related quality of life (HRQoL) and considered suitable for patients with asthma. In 2009, the EuroQol Group developed a new EQ-5D version to overcome limitations related to its consistently reported high ceiling effect. To enhance the sensitivity for assessing the HRQoL in further patient populations, the number of responses of EQ-5D was increased from 3 to 5 levels (EQ-5D-5L). Moreover, the availability of well-defined requirements for its Web-based administration allows EQ-5D-5L use to monitor the HRQoL in electronic health (eHealth) programs. No study has evaluated the metric properties of the new EQ-5D-5L in patients with asthma yet. OBJECTIVE: This study aims to examine the distribution, construct validity, and reliability of the new EQ-5D-5L questionnaire administered online to adults with asthma. METHODS: We evaluated patients with asthma (age: 18-40 years) from a primary care setting in France and England, who self-completed the EQ-5D-5L questionnaire online. The inclusion criteria were persistent asthma defined as >6 months of prescribed inhaled corticosteroids and long-acting beta-agonists or inhaled corticosteroids alone during the 12 months prior to inclusion. The EQ-5D index was obtained by applying the English preference value set for the new EQ-5D-5L and the French 3L-5L crosswalk value set. Both value sets produced single preference-based indices ranging from 1 (best health state) to negative values (health states valued as worse than death), where 0=death, allowing the calculation of quality-adjusted life years. Responses to dimensions and index distribution, including ceiling and floor effects, were examined. The construct validity was assessed by comparing the means of known groups by analyses of variance and calculation of effect sizes. RESULTS: Of 312 patients answering the baseline Web-based survey, 290 completed the EQ-5D-5L (93%). The floor effect was null, and the ceiling effect was 26.5% (74/279). The mean EQ-5D-5L index was 0.88 (SD 0.14) with the English value set and 0.83 (SD 0.19) with the French 3L-5L crosswalk value set. In both indices, large effect sizes were observed for known groups defined by the Asthma Control Questionnaire (1.06 and 1.04, P<.001). Differences between extreme groups defined by chronic conditions (P=.002 and P=.003 for the English value set and French 3L-5L crosswalk value set, respectively), short-acting beta-agonists (SABAs) canisters in the last 12 months (P=.02 and P=.03), or SABA use during the previous 4 weeks (P=.03 and P=.01) were of moderate magnitude with effect sizes around 0.5. CONCLUSIONS: The new EQ-5D-5L questionnaire has an acceptable ceiling effect, a good construct validity based on the discriminant ability for distinguishing among health-related known groups, and high reliability, supporting its adequacy for assessing the HRQoL in patients with asthma. EQ-5D-5L completion by most Web-based respondents supports the feasibility of this administration form.

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.

Limited treatment adaptation despite poor asthma control in asthma patients treated with inhaled corticosteroids.

OBJECTIVE: Current asthma guidelines recommend use of inhaled corticosteroids (ICS) in patients with persistent disease. This study was designed to investigate (1) the proportion of patients prescribed ICS-containing maintenance treatment who achieve asthma control, (2) determinants of control and (3) how physicians adapt treatment to the level of control. METHODS: General practitioners (GPs) and chest physicians (CPs) in France recruited patients consulting for asthma and prescribed an ICS. Over a 2-year follow-up period, asthma symptoms in the previous 3 months and treatments prescribed were documented at each visit. Variables independently associated with asthma control were determined by multiple logistic regression. RESULTS: Data were available for 924 patients recruited by GPs and 455 recruited by CPs. Asthma control was acceptable in only 24% of patients at inclusion, and in 33.6% at the last follow-up visit. Five factors were independently associated with asthma control: age (or time since diagnosis), gender, smoking status, allergic aetiology of asthma and treatment. Most patients (56.3%) were prescribed the same ICS dose regimen at the end of follow-up as at inclusion. The intensity of controller therapy had been increased in only 12.2% of patients unacceptably controlled at inclusion. CONCLUSIONS: Asthma was unacceptably controlled in most patients receiving ICS-containing maintenance treatment and remained so during follow-up. Despite this, treatment adaptations by GPs and CPs were very infrequent. This unsatisfactory situation may be improved by adopting a more dynamic approach to tailoring controller therapy to the needs of the patient.

[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.

Prescription of antibiotics and anxiolytics/hypnotics to asthmatic patients in general practice: a cross-sectional study based on French and Italian prescribing data.

BACKGROUND: Asthma is often poorly controlled and guidelines are often inadequately followed in medical practice. In particular, the prescription of non-asthma-specific drugs can affect the quality of care. The goal of this study was to measure the frequency of the prescription of antibiotics and anxiolytics/hypnotics to asthmatic patients and to look for associations between sex or age and the prescription of these drugs. METHODS: A cross-sectional study was conducted using computerised medical records from French and Italian general practitioners' networks. Patients were selected according to criteria adapted from the HEDIS (Healthcare Effectiveness Data and Information Set) criteria. The outcome measure was the number of antibiotics or anxiolytics/hypnotics prescriptions per patient in 1 year. Parallel multivariate models were developed. RESULTS: The final sample included 3,093 French patients (mean age 27.6 years, 49.7% women) and 3,872 Italian patients (mean age 29.1 years, 48.7% women). In the univariate analysis, the French patients were prescribed fewer antibiotics than the Italian patients (37.1% vs. 42.2%, p < 0.00001) but more anxiolytics/hypnotics (17.8% vs. 6.9%, p < 0.0001). In the multivariate models, the female patients were more likely to receive antibiotics (odds ratio: 1.5 [1.3-1.7]) and anxiolytics/hypnotics (odds ratio: 1.8 [1.5-2.1]). CONCLUSIONS: The prescription of antibiotics and anxiolytics/hypnotics to asthmatic patients is frequent, especially in women. Asthma guidelines should address this issue by referring to other guidelines covering the prescription of non-asthma-specific drugs, and alternative non-pharmacological interventions should be considered.

Asthma drug ratios and exacerbations: claims data from universal health coverage systems.

In claims data, controller-to-total asthma drug ratios may reflect adequacy of disease management. We verified whether asthma patients with high ratios (≥ 50%) experienced fewer asthma-related outcomes. Two ratios were studied: that of the inhaled corticosteroids to total asthma drug (ICS/R03) and that of the inhaled corticosteroids plus leukotriene antagonist receptors-to-total asthma drug (ICS+LTRA/R03). Patients aged 13-40 years, with ≥ 3 respiratory drugs dispensed prescriptions in 2005 were selected from the French national claims data. After excluding null ratios, two groups were defined according to ratio values in 2007: low-ratio group (0% < ratio < 50%) and high-ratio group (ratio ≥ 50%). For both ratios, asthma-related outcomes and medical-resource utilisation were compared between groups. Of 2162 patients (mean age 27 years and 52% female), patients with non-null ratios were 81% and 85% for ICS/R03 and ICS+LTRA/R03 ratios, respectively. Patients with high ratios were less likely to receive oral corticosteroids than those in the low-ratio group (relative risk 0.79, 95% CI 0.72-0.88, and 0.80, 95% CI 0.72-0.88, for ICS/R03 and ICS+LTRA/R03, respectively). High ratio groups also presented fewer asthma-related hospitalisations. Significant negative correlations were also observed for both ratios, when studied quantitatively, according to patients' dispensed level of oral corticosteroids in 2007. In claims data, both ICS/R03 and ICS+LTRA/R03 ≥ 50% were related to fewer asthma-related outcomes. Ratios should be explored to identify asthma patients at risk of exacerbations. Low ratios can be considered as risk factors of exacerbation whatever the underlying cause.

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.

Real-life use of fluticasone propionate/salmeterol in patients with chronic obstructive pulmonary disease: a French observational study.

BACKGROUND: In Europe, administration of an inhaled corticosteroid (ICS) combined with a long-acting ß2 agonist is approved in chronic obstructive pulmonary disease (COPD) patients with a pre-bronchodilator FEV1 < 60% predicted normal, a history of repeated exacerbations, and who have significant symptoms despite regular bronchodilator therapy. Minimal data are available on the use of the fluticasone propionate/salmeterol xinafoate combination (FSC) in the real-life COPD setting and prescription compliance with the licensed specifications. METHODS: A French observational study was performed to describe the COPD population prescribed with FSC, prescription modalities, and the coherence of prescription practices with the market authorized population. Data were collected for patients initiating FSC treatment (500 µg fluticasone propionate, 50 µg salmeterol, dry powder inhaler) prescribed by a general practitioner (GP) or a pulmonologist, using physician and patient questionnaires. RESULTS: A total of 710 patients were included, 352 by GPs and 358 by pulmonologists. Mean age was over 60 years, and 70% of patients were male. More than half were retired, and overweight or obese. Approximately half were current smokers and one-third had cardiovascular comorbidities. According to both physician evaluation and GOLD 2006 classification, the majority of patients (>75%) had moderate to very severe COPD. Strict compliance by prescribing physicians with the market-approved population for dry powder inhaler SFC in COPD was low, notably in ICS-naïve patients; all three conditions were fulfilled in less than a quarter of patients with prior ICS and less than 7% of ICS-naïve patients. CONCLUSIONS: Prescription of dry powder inhaler SFC by GPs and pulmonologists has very low conformity with the three conditions defining the licensed COPD population. Prescription practices need to be improved and systematic FEV1 evaluation for COPD diagnosis and treatment management should be emphasized.

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.

Evidence on the global measurement model of the Minnesota Living with Heart Failure Questionnaire.

PURPOSE: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used health-related quality of life measure in both clinical and research settings. Nevertheless, its measurement model has never been confirmed. This study aims to fill that gap with a large international sample. METHODS: Data from eight studies (3,847 patients with heart failure) from 21 countries were merged and analysed. Common variables included MLHFQ scores, functional capacity, cardiovascular risk factors and the socio-demographic characteristics of the patient. The measurement model of the MLHFQ was assessed by means of exploratory and confirmatory factor analyses (EFA-CFA). The reliability of MLHFQ scores was evaluated using Cronbach's alpha coefficient and the MLHFQ's ability to differentiate among known groups was assessed through severity levels. RESULTS: Findings from the EFA and CFA suggest that the MLHFQ total and domain-specific scores fall within a bifactor model. The physical and emotional scores were supported within the sample, as was the original total score. Furthermore, a third factor was revealed regarding social environment. The reliability coefficient reached 0.9 for almost all physical and total scores. All the MLHFQ mean scores showed the ability to differentiate among functional capacity groups, with most of the effect size coefficients reaching 0.8. CONCLUSIONS: Beyond the suitable degree of reliability and validity displayed by the MLHFQ scores in the different country-specific versions, our results confirmed for the first time the unidimensionality of the most commonly used score in HF patients: the total MLHFQ score. Moreover, the social environment domain identified in this study can now be considered when assessing these patients' HRQL, especially as a relevant outcome with regard to disease management.

Factors associated with early adherence to tiotropium in chronic obstructive pulmonary disease.

Tiotropium is an innovative intervention in chronic obstructive pulmonary disease (COPD). Early adherence to tiotropium remains inadequately explored, notably time from initiation to discontinuation (persistence). In patients with COPD, the factors associated with the risk of discontinuing the treatment with tiotropium within 12 months following initiation were identified (12-month persistence). Claim databases from the French Social Security were used. A random sample of patients (aged 50-80 years) who initiated tiotropium soon after launch was selected. Factors associated with the persistence were investigated (Log-rank test and multivariate Cox model). Of the 1147 newly treated patients (mean age 68 years, 33% women), 64% remained in the treatment of tiotropium for over a period of 12 months following initiation. More than 10% of the patients interrupted therapy after a single dispensing, most often those with mild COPD. Lower risks of discontinuing tiotropium within 12 months following initiation were observed when it was initiated by a private sector specialist (hazard ratio (HR) = 0.65, 95% confidence interval (CI) = (0.52-0.82)), by hospital-based physician (HR = 0.58, 95% CI = (0.42-0.78)), when ≥ 2 other respiratory drugs were associated (HR = 0.74, 95% CI = (0.58-0.95)) and in case of long-term disease status (HR = 0.78, 95% CI = (0.63-0.97)). Conversely, no clear effect appeared according to age or gender. In this population of patients with COPD, fewer early discontinuations of tiotropium were observed in patients having a severe condition.

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.