Multiple Biologics for Multiple T2 Diseases: A Pharmacoepidemiological Algorithm for Sorting Out Patients by Indication.

Background: Several biologics (Bx) and targeted synthetic drugs (TSD) exist to treat T2 diseases, including chronic spontaneous urticaria (CSU), severe asthma (SA), chronic rhinosinusitis with nasal polyposis (CRSwNP) or atopic dermatitis (AD). Objective: To identify patients treated with Bx/TSD from a dynamic dispensing database using an algorithm-based methodology. Methods: We used the LRx database (Lifelink Treatment dynamics, IQVIA) which covers nearly 45% of the French retail pharmacies. Patients who had at least one Bx/TSD dispensing from April 2021 to March 2022 were included. An algorithm was designed to determine the indication of the Bx/TSD prescription analyzing all previous drug dispensation since March 2012 following a 3-steps procedure. Results: A total of 21,677 patients received at least one Bx/TSD between March 2021 and April 2022. The algorithm identified 91.7% (n = 19,884) patients with a T2 disease (AD = 18.4%, CRSwNP = 1.5%, SA = 59.5%, and CSU = 12.4%), the rest having either an association of diseases (1%) or an undetermined one (7.3%). SA was the main reason for Bx/TSD initiation (52%), followed by AD (29%), CSU (14%) and CRSwNP (5%). For SA patients already under biologic at entry, omalizumab was the most frequently prescribed (48%) followed by benralizumab, mepolizumab (22% each) and dupilumab (8%). Dupilumab was mostly prescribed for AD patients (89% for patient-initiated vs 96% for patient-renewed) followed by baricitinib. Conclusion: The algorithm was able to identify patients with T2 diseases under Bx/TSD treatments. This tool may help to follow the evolution of prescription patterns in the future.

Artificial intelligence to differentiate asthma from COPD in medico-administrative databases.

INTRODUCTION: Discriminating asthma from chronic obstructive pulmonary disease (COPD) using medico-administrative databases is challenging but necessary for medico-economic analyses focusing on respiratory diseases. Artificial intelligence (AI) may improve dedicated algorithms. OBJECTIVES: To assess performance of different AI-based approaches to distinguish asthmatics from COPD patients in medico-administrative databases where the clinical diagnosis is absent. An "Asthma COPD Overlap" category was defined to further test whether AI can detect complexity. METHODS: This study included 178,962 patients treated by two "R03" treatment prescriptions at least from January 2016 to December 2018 and managed by either a general practitioner and/or a pulmonologist participating in a permanent longitudinal observatory of prescription in ambulatory medicine (LPD). Clinical diagnoses are available in this database and were used as gold standards to develop diagnostic rules. Three types of AI approaches were explored using data restricted to demographics and treatment dispensations: multinomial regression, gradient boosting and recurrent neural networks (RNN). The best performing model (based on metric properties) was then applied to estimate the size of asthma and COPD populations based on a database (LRx) of treatment dispensations between July, 2018 and June, 2019. RESULTS: The best models were obtained with the boosting approach and RNN, with an overall accuracy of 68%. Performance metrics were better for asthma than COPD. Based on LRx data, the extrapolated numbers of patients treated for asthma and COPD in France were 3.7 and 1.2 million, respectively. Asthma patients were younger than COPD patients (mean, 49.9 vs. 72.1 years); COPD occurred mostly in men (68%) compared to asthma (33%). CONCLUSION: AI can provide models with acceptable accuracy to distinguish between asthma, ACO and COPD in medico-administrative databases where the clinical diagnosis is absent. Deep learning and machine learning (RNN) had similar performances in this regard.

"Real-life" management of patients with severe asthma in the biologics era: Can we do better?

BACKGROUND: Discrepancies exist between guidelines and real-life practice in severe asthma. Objectives: To establish profiles for severe asthma patients according to their maintenance therapies and identify unmet needs. METHODS: 2432 French lung specialists and allergists were invited to participate in a severe asthma survey between March and April 2018. Retrospective data were collected using an electronic case report form developed by IQVIA. RESULTS: 71 respiratory physicians and/or allergists participated in the study, providing data for 736 severe asthma patients. The annual mean rates of hospitalization and exacerbation in the previous year were 0.65 (SD = 0.5) and 2.25 (SD = 1.0), respectively. One hundred one (13.7%) patients were treated with oral steroids; the mean dosage regimen was 16.1 mg per day (SD = 11.2). ICS-LABA-LAMA triple inhaled therapy was reported for 288 patients (39%); 231 patients (31.4%) had one biologic in their maintenance treatment. Among patients hospitalized at least once in the previous year (n = 311), 89 (28.5%) were currently treated with biologics, and 61 (19.6%) with oral steroids. One hundred sixty-six patients with uncontrolled asthma and no current biologic therapy had data for "T2 status"; 78 (47%), 89 (53.6%) and 137 (82.5%) of them had treatment criteria respectively for an anti-IgE, anti-IL5-pathway or anti-IL-4/IL-13 pathway therapy; 22 (13.2%) were ineligible for any current biologic according to biomarkers. CONCLUSION: Our study updated "real-life" therapeutic management data for severe asthma in France in 2018. We highlighted a need for improved patient-phenotyping. This work also gives a striking insight of the position of current and forthcoming biologics.

Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses.

Importance: An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied. Objective: To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest. Design, Setting, and Participants: A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018. Exposure: Continuous PPI use during the 2015 to 2016 AGE winter epidemic. Main Outcomes and Measures: The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions. Results: There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older. Conclusions and Relevance: Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.

Cross-validation of an algorithm detecting acute gastroenteritis episodes from prescribed drug dispensing data in France: comparison with clinical data reported in a primary care surveillance system, winter seasons 2014/15 to 2016/17.

BACKGROUND: This study compares an algorithm to detect acute gastroenteritis (AG) episodes from drug dispensing data to the validated data reported in a primary care surveillance system in France. METHODS: We used drug dispensing data collected in a drugstore database and data collected by primary care physicians involved in a French surveillance network, from season 2014/15 to 2016/17. We used an adapted version of an AG discrimination algorithm to identify AG episodes from the drugstore database. We used Pearson's correlation coefficient to evaluate the agreement between weekly AG signals obtained from the two data sources during winter months, in the overall population, by specific age-groups and by regions. RESULTS: Correlations between AG signals for all ages were 0.84 [95%CI 0.69; 0.92] for season 2014/15, 0.87 [95%CI 0.75; 0.93] for season 2015/16 and 0.94 [95%CI 0.88; 0.97] for season 2016/17. The association between AG signals estimated from two data sources varied significantly across age groups in season 2016/17 (p-value < 0.01), and across regions in all three seasons studied (p-value < 0.01). CONCLUSIONS: There is a strong agreement between the dynamic of AG activity estimated from drug dispensing data and from validated primary care surveillance data collected during winter months in the overall population but the agreement is poorer in several age groups and in several regions. Once automated, the reuse of drug dispensing data, already collected for reimbursement purposes, could be a cost-efficient method to monitor AG activity at the national level.

Knee replacement incidence and social deprivation: results from a French ecological study.

OBJECTIVES: Temporal and geographic variations in knee osteoarthritis (OA) incidence occur worldwide. Regional variations also exist for socioeconomic status. We analyzed the association between socioeconomic deprivation (SED) and knee replacement (KR) incidence and assessed the proportion of KR associated with affluence. METHODS: Patients aged 15 years and over hospitalized for KR in 2013 were included. We linked each patient to a municipality of residence. Municipalities were matched to the 2011 European Deprivation Index score for SED analysis. Poisson regression was performed to examine the association between KR incidence and EDI adjusted for age and sex. The Population Attributable Fraction (PAF) was measured to calculate the proportion of excess of KR associated with social affluence. RESULTS: We included 77 597 KR. KR incidence decreased with increasing SED index. The EDI was significantly associated with KR incidence (P < 0.0001). The risk of KR is 2.36 times higher for persons living in the most affluent area compared to those living in the most underprivileged area. The PAF was 28.3%. CONCLUSIONS: The French administrative municipalities with the highest SED have the lowest age- and sex-adjusted KR incidence. It cannot be excluded that patients living in more privileged areas are overtreated. Complementary studies are necessary to define all the individual factors that limit or increase the access to knee replacement.

Persistent clinical inertia in gout in 2014: An observational French longitudinal patient database study.

OBJECTIVE: To describe the characteristics and management of patients with gout in France during the year 2014. METHODS: Data were obtained from a computerized observational longitudinal patient database of a representative sample of 1200 general practitioners. Patients on urate-lowering treatment and/or colchicine were described by demographics and comorbidities, quality of management indicators (serum uric acid and renal function testing) and treatment (type of urate-lowering treatment, change and dose regimen). RESULTS: We identified 14,400 patients (84.4% men, mean age: 67.5 years) with gout in the database. The most frequent comorbidities were hypertension (70%), dyslipidemia (51%), diabetes (24%) and obesity (23%). The proportion with uric acid and renal function testing data was 32% and 29%, respectively. In gout patients, only 39% had a serum uric acid<6mg/dL. Among treated gout patients, 76% were receiving allopurinol at a mean dose lower than 200mg/d, most without any further change of dose regimen over one year. CONCLUSION: These data outlined the persistence of clinical inertia in 2014 for patients with gout.

Changes in number and incidence of hip fractures over 12 years in France.

The incidence of hip fractures decreased in France in both genders, especially in the elderly, from 2002 to 2008, in parallel with availability of bone densitometry and effective anti-osteoporotic treatments. However prescriptions of these treatments are decreasing, since 2008, and recent studies show declining of osteoporosis management after fragility fractures. The aim of this study was to assess the incidence of hip fractures in men and women aged 60 years and over, from 2002 to 2013 in France. Data were drawn from the French Hospital National Database which includes all hospitalizations of the country. Hospital data for hip fractures between 2002 and 2013 were numbered and the incidence rates per 1,000,000 adjusted on age (60-74; 74-84, and ≥ 85 years), and gender was calculated using the data of the French population. The number of hip fractures increased in women (+5%; from 49,287 in 2002 to 50,215) and in men (+22%, from 12,716 to 15,482) aged over 60 years. Between 2002 and 2013, the French population increased by 21 and 29% in women and men of this age group; thus, incidence of hip fractures decreased by 14% in women (6929 and 5987 per million in 2002 and 2013, respectively) and a slight decrease of -1% was observed in men (2344 and 2316). The decrease in incidence is also confirmed in the very elderly (≥ 85 years), with a decrease of -29% and -24% in women and men respectively. Over the last 12 years, the incidence of hip fractures decreased in France in women and men aged over 60 years. This decrease is also observed in the subjects (≥ 85 years and older in both genders). Further studies are needed to assess potential changes in risk factors of hip fractures during the last decade.

Impact on costs of switching one-ray aponeurectomy to percutaneous needle aponeurotomy in Dupuytren's disease: A model analysis.

OBJECTIVE: To assess the cost of switching surgical aponeurectomy to percutaneous needle aponeurotomy in one-ray Dupuytren's disease. METHODS: A model analysis was performed with a cross-sectional national survey of public and private French hospitals in 2012. All stays for one-ray aponeurectomy were "virtually" replaced with 1, 2 or 3 outpatient sessions of percutaneous needle aponeurotomy. The costs were based on the hospital cost (tariff per disease-related group) and on common classification of medical procedures performed in outpatient care for 2013. RESULTS: Dupuytren's disease represented 18,707 hospitalizations (€26 million [2013 euros]) in France in 2012, 8534 hospitalizations for one-ray aponeurectomy (€11.9 million). By replacing surgical aponeurectomy with percutaneous needle aponeurotomy for one-ray Dupuytren's disease, 91% to 97% and 56% to 59% of the treatment costs could be saved using hospitalizations for one-ray aponeurectomy or total hospital costs, respectively, as reference. CONCLUSIONS: Replacing aponeurectomy with percutaneous needle aponeurotomy for one-ray Dupuytren's disease could greatly reduce the treatment costs for all Dupuytren's disease. Effective alternatives to surgery for Dupuytren's disease, such as needle aponeurotomy in an outpatient setting should be considered in the economic perspective.

Hospital burden of gout, pseudogout and other crystal arthropathies in France.

OBJECTIVE: To describe the hospital burden of microcrystal arthropathies in France. METHODS: Data were extracted from the 2009-2011 French hospital national databases. We selected all hospital stays for microcrystal arthropathies (gout, chondrocalcinosis, other) encoded as primary or secondary diagnoses in patients older than 18. A descriptive analysis focused on number of patients and hospital stays, age, gender, comorbidities related to metabolic syndrome, and hospital costs based on 2012 public-sector costs. RESULTS: 132,275 hospitalizations involving 109,734 patients were related to microcrystal arthropathies encoded as primary or secondary diagnosis (61% related to gout, 34% to chondrocalcinosis, and 5% to other microcrystal arthropathies). 23,362 hospitalizations involving 25,105 patients were due to microcrystal diseases, encoded as primary diagnosis, (48% related to gout, 43% to chondrocalcinosis, and 9% to other microcrystal arthropathies). In this population, patients with chondrocalcinosis were older (mean 75.6±13.5 versus 71±16 years for other microcrystal arthropathies and 69.7±14.7 for gout). Men represented 70% of the patients with gout, 39% of those with chondrocalcinosis and 52% of the patients with other microcrystal arthropathies. Hypertension, diabetes, dyslipidemia, cardiac ischemia, and renal failure were more frequent in patients with gout than other patients. The hospital costs for microcrystal arthropathies encoded as primary diagnosis were 82.3 million Euros, 45% related to gout, 45% to chondrocalcinosis and 11% to other microcrystals. CONCLUSION: In terms of hospital costs, gout and chondrocalcinosis represented the main part of the economic burden of crystal arthropathies and a high level of diseases belonging to the metabolic syndrome. Specific education programs favouring accurate microcrystal diagnosis and adherence to treatment could diminish this hospital economic burden.

Economic burden of osteoporosis in women: data from the 2008 French hospital database (PMSI).

OBJECTIVES: To estimate the number and costs of hospitalisations associated with osteoporosis in France. METHODS: Data for women aged 50 years and over were extracted from the 2008 French Hospital National Database. Criteria for acute care were established according to ICD-10 codes related to osteoporosis. As coding rules are not systematically used, an additional extraction which included surgical stays for hip fractures was performed in order to be more exhaustive. The two datasets were merged and duplicate stays excluded. Among women hospitalised in acute care during 2008, we selected those progressing to rehabilitation care within the year. We assessed the numbers of hospitalisations and women, proportion of surgical management, length of stay in acute care and numbers of rehabilitation days and costs. Hospital costs were calculated according to the National Hospital Tariff and National Scale of Costs, respectively, for acute and rehabilitation care based on 2009 tariffs. RESULTS: There were 67.807 hospitalisations (64.793 patients) associated with osteoporosis; 83% of total hospitalisations were in patients aged ≥75 years. A total of 80% of hospitalisations were associated with surgical management of fractures and 31.458 patients (49%) progressed from hospitalisation to rehabilitation. The mean ±SD length of stay was 12±8 days for hospitalisation and 43±31 days for rehabilitation care. The overall cost of hospitalisations was €415.4 million, of which 4.2% was related to medical devices. The overall cost of rehabilitation was €331.8 million. CONCLUSIONS: In 2008, postmenopausal osteoporosis was associated with a substantial economic burden at hospital in France.

Subtrochanteric/femoral shaft versus hip fractures: incidences and identification of risk factors.

Subtrochanteric and femoral shaft (ST/FS) fractures are now considered to be fragility fractures in osteoporotic patients. Although rare, there is growing evidence of the burden that they constitute. Little is known about the change over time in incidence of ST/FS fractures. We assessed the incidence of ST/FS fractures and the associated risk factors from 2002 to 2009 compared with those of hip fractures. Data were obtained from the French National Database, which includes all hospital discharge codes from acute care facilities. Hospitalizations for primary surgical management of neck/trochanteric (hip) and ST/FS fractures in patients aged above 50 years were selected and described for different age groups. Incidences per million populations were calculated using the estimated French population adjusted for each year, age, and gender. We studied the change for each fracture site. The comorbidity factors related to these fractures were assessed in 2009 using multivariate logistic regression. From 2002 to 2009, the adjusted incidence of hip fractures decreased continuously from 4368 to 3662 in women (p < 0.0001), and a mild increase from 1476 to 1384 in men (p < 0.0001) after an initial decrease. In contrast, the incidence of ST/FS increased significantly in both genders (from 353 to 395 in women, from 146 to 159 in men). In 2009, the incidence of ST/FS in the general population remained low, reaching the levels of 412 in women and 168 in men, but were 2966 and 1461 in women and men aged >89 years. The adjusted risk of having a ST/FS fracture was significantly higher in a context of obesity (odds ratio [OR]: 2.26; 1.95-2.61) and dementia (OR: 1.23; 1.16-1.30), but decreased with age (OR: 0.83; 0.79-0.88) and hypertension (OR: 0.90; 0.86-0.95). In conclusion, ST/FS fractures mainly affect elderly people and incidence increased significantly from 2002 to 2009. Obesity and dementia are the risk factors associated with these rare fractures, compared with regular hip fractures.

International survey of primary and revision total knee replacement.

PURPOSE: Total knee arthroplasty (TKA) is currently the international standard of care for treating degenerative and rheumatologic knee joint disease, as well as certain knee joint fractures. We sought to answer the following three research questions: (1) What is the international variance in primary and revision TKA rates around the world? (2) How do patient demographics (e.g., age, gender) vary internationally? (3) How have the rates of TKA utilization changed over time? METHODS: The survey included 18 countries with a total population of 755 million, and an estimated 1,324,000 annual primary and revision total knee procedures. Ten national inpatient databases were queried for this study from Canada, the United States, Finland, France, Germany, Italy, the Netherlands, Portugal, Spain, and Switzerland. Inpatient data were also compared with published registry data for eight countries with operating arthroplasty registers (Denmark, England & Wales, Norway, Romania, Scotland, Sweden, Australia, and New Zealand). RESULTS: The average and median rate of primary and revision (combined) total knee replacement was 175 and 149 procedures/100,000 population, respectively, and ranged between 8.8 and 234 procedures/100,000 population. We observed that the procedure rate significantly increased over time for the countries in which historical data were available. The compound annual growth in the incidence of TKA ranged by country from 5.3% (France) to 17% (Portugal). We observed a nearly 27-fold range of TKA utilization rates between the 18 different countries included in the survey. CONCLUSION: It is apparent from the results of this study that the demand for TKA has risen substantially over the past decade in countries around the world.

Decrease of inpatient mortality for hip fracture in France.

OBJECTIVE: Hip fracture is the most devastating osteoporotic fracture, increasing the risk of mortality. Recent data suggest a decrease in incidence of this fracture. Few data are available on potential changes in mortality. We studied the change of inpatient mortality from 2002 to 2008 in France. METHODS: Data were extracted from the French Hospital National Database. The absolute number of inpatient mortality for hip fracture was described as well as the case fatal rate and mortality rate adjusted on age and gender. Risk factors of inpatient mortality were assessed by multiple regressions. RESULTS: Inpatient mortality stay decreased from 3057 to 2350 in patients aged 40 years and over and in both gender. Inpatient mortality stays were more important in women and increased with age, but the case fatal rate was higher in men than in women (5.4 vs. 2.8% in 2008). During the study period, the mortality rate (per 1,000,000) varied from 132 to 88 and from 82 to 64 in women and men, respectively. In the older patients, case fatality and mortality rates decreased significantly during the study period. From 2008 data, age more or equal to 85 years, male gender, stay in intensive care and existence of some chronic or acute disease, especially cardiovascular disease, hepatic disease, renal insufficiency, and infection were significant determinants of inpatient mortality. CONCLUSION: Inpatient mortality after hip fracture decreased in France between 2002 and 2008, although age, male gender and comorbidities were identified as determinants of inpatient mortality.

Economic impact of rheumatoid arthritis (RA) biotherapies in France.

OBJECTIVE: Determining the economic impact of rheumatoid arthritis (RA) biotherapies in France. METHOD: The number of patients on RA biotherapy in France was estimated from the French national medical information system program (PMSI) database using the 2007 hospital data. The cost of each biotherapy was calculated on a theoretical basis (French national health authority (HAS) recommendations) and on real-life setting, using 'real-life' setting data. In order to calculate the economic impact of the biotherapies, the cost of management with each biotherapy was applied to the RA patient population taking into account the market share of each biotherapy. RESULTS: The number of patients with RA estimated was 15,873. Management costs ranged from 11,576 to 21,128 euro for the theoretical management scenario and from 6,451 to 19,618 euro for the real-life scenario. The overall cost was 222 million euro (real-life setting). TNF antagonists (adalimumab, etanercept, infliximab) were prescribed for 82% of the patient population and accounted for 80% of the annual overall cost of theoretical management and 84% of the cost of the real-life setting, respectively. Other biotherapies (abatacept, rituximab) were prescribed for 18% of the patients and accounted for 20 and 16% of the annual overall cost of the theoretical setting and real-life setting. Outpatient biotherapy was prescribed for 61% of the patient population and generated 68 and 71% of the total costs. CONCLUSION: The data constitutes an initial inventory of the economic impact of RA biotherapies in France.