COVID-19 and pregnancy: A European study on pre- and post-infection medication use.

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

Incidence and risk of cancer among multiple sclerosis patients: A matched population-based cohort study.

BACKGROUND AND PURPOSE: Studies have not yet found conclusive results on the risk of cancer in patients with multiple sclerosis (MS). This study aimed to compare the incidence of all cancers and of specific types of cancer between MS patients and the general population by age and by sex. METHODS: All prevalent MS patients identified between 2008 and 2014 in the nationwide French health care database (Système National des Données de Santé) and without history of malignancy were included in a cohort study and followed up until cancer occurrence, date of death, or 31 December 2015, whichever came first. MS patients were matched based on sex and year of birth to non-MS controls from the general population without cancer before index date. Incidence rate was reported per 100,000 person-years (PY), and risk of cancer was estimated by type of cancer, age, and sex using a Cox model (hazard ratio [HR] and its 95% confidence interval [CI]). RESULTS: Overall, 576 cancers per 100,000 PY were observed in MS patients versus 424 per 100,000 PY in the control population. The risk of cancer was higher among MS patients than among population controls whether considered overall (HR = 1.36, 95% CI = 1.29-1.43) or for prostate (HR = 2.08, 95% CI = 1.68-2.58), colorectal and anal (HR = 1.35, 95% CI = 1.16-1.58), trachea, bronchus, and lung (HR = 2.36, 95% CI = 1.96-2.84), and to a lesser extent, breast cancer (HR = 1.12, 95% CI = 1.03-1.23). CONCLUSIONS: MS patients were associated with increased risk of cancer compared to population controls.

Effectiveness of first-line cetuximab in wild-type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort.

AIMS: Poor efficacy has been reported for patients with BRAF mutations for metastatic colorectal cancer (mCRC). METHODS: EREBUS is a French cohort study of wild-type (wt) KRAS unresectable mCRC patients initiating a first-line treatment with cetuximab from 2009 to 2010, followed for two years (five years for vital status). Molecular genetics platforms have provided additional RAS and BRAF mutation testing results. Progression-free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status: RASmt/BRAFany, RASwt/BRAFmt and RASwt/BRAFwt. Multivariate Cox analyses were used to evaluate association between mutation status and death or progression. RESULTS: A total of 389 patients were included in 65 centres and with a known tumour mutation status: 64 RASmt/BRAFany (21%), 33 RASwt/BRAFmt (13%) and 213 RASwt/BRAFwt (87%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, Eastern Cooperative Oncology Group performance status ≤ 1 75%, 76% and 79%, and liver-only metastases 39%, 33% and 40%. Median progression-free survival was 8.0 months [5.9-9.3] for patients with RASmt/BRAFany, 6.0 months [2.3-7.2] for patients with RASwt/BRAFmt, and 10.4 months [9.5-11.0] for patients with RASwt/BRAFwt. Respectively, median overall survival was 18.4 months [10.9-23.3], 9.7 months [6.9-16.6] and 29.3 months [26.3-36.1]. In multivariate analyses, progression (HR = 2.71 [1.79-4.10]) and death (HR = 2.79 [1.81-4.30]) were more likely for RASwt/BRAFmt vs RASwt/BRAFwt patients. CONCLUSIONS: BRAF mutations were associated with markedly poorer outcomes in initially unresectable RASwt mCRC patients treated by cetuximab in first-line treatment.

Intra-database validation of case-identifying algorithms using reconstituted electronic health records from healthcare claims data.

BACKGROUND: Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. OBJECTIVES: To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). METHODS: Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. RESULTS: Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. CONCLUSION: The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.

Pharmacological treatment patterns in heart failure: a population-based cohort study.

BACKGROUND: Although the efficacy and safety of existing therapies of heart failure (HF) have been demonstrated in clinical trials, little is known about the treatment patterns in clinical practice, especially in France. OBJECTIVES: To describe the treatment initiation patterns and the subsequent treatment changes among HF patients, in the first year following an incident hospitalization for HF, in a French real-world setting. METHODS: A cohort of patients aged ≥ 40 years, with an incident hospitalization for HF between 01/01/2008 and 31/12/2013, was identified in the 1/97th permanent random sample of the French nationwide claims database and followed 1 year. HF drug exposure-beta blockers (BB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), aldosterone antagonists (AA), diuretics, digoxin, or ivabradine-was assessed quarterly using a Proportion of Days Covered ≥ 66% (≥ 60 days out of the 90 days of the quarter), by considering HF drugs individually or in combination. Drug changes were assessed between each quarter. RESULTS: Between 2008 and 2013, 7387 patients were included. Their mean age was 77.7 years (± 12.0 years) and 51.6% were women. During the follow-up, 24.4% died, 20% were not exposed to any HF treatment, 48.3 to 43.2% had diuretics, one third had BB or ACEI, 9% had ARB or AA, 6% had digoxin, and 2% had ivabradine. The main change occurred between the first and the second quarter for 53.1% of the initially untreated patients. CONCLUSION: This study provides valuable information on treatment patterns after an initial hospitalization for HF.

Overall and progression-free survival with cabazitaxel in metastatic castration-resistant prostate cancer in routine clinical practice: the FUJI cohort.

BACKGROUND: Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel. METHODS: Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months. RESULTS: Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1-12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia. CONCLUSION: Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m2, median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identified. STUDY REGISTRATION: It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.

Outcomes in patients after myocardial infarction similar to those of the PEGASUS-TIMI 54 trial: A cohort study in the French national claims database.

AIMS: The present study aims to describe real-life outcomes in stable patients after-myocardial infarction (MI) similar to those in the PEGASUS-TIMI 54 trial (PEGASUS), which found long-term benefits of ticagrelor in patients with a history of MI. METHODS: One-year event-free post-MI patients were identified in the French claims database representative 1/97 sample (2005-2010) and followed for up to 3 years. A PEGASUS-like (PL) population included patients with age ≥ 65 years, or age ≥ 50 and diabetes, renal dysfunction or prior MI, without stroke, end-stage renal failure or oral anticoagulation. Outcomes were: a composite of all-cause death or hospital admission for MI or stroke; individual events; major bleeding. RESULTS: There were 1585 post-MI patients totalling 3926 person-years including 865 PL patients (2114 PY); 68% were male; mean age was 66 (standard deviation 15) in post-MI, 74 (10) in PL. Outcomes per 100 person-years [95% confidence interval] were, respectively, in post-MI and PL 6.3 [5.6-7.1] and 7.8 [6.7-8.9] for the composite outcome; 5.1 [4.4-5.8] and 6.5 [5.5-7.6] for death; 1.0 [0.7-1.3] and 1.0 [0.6-1.4] for MI; 0.6 [0.4-0.9] and 0.9 [0.5-1.2] for stroke; 1.3 [0.9-1.6] and 1.4 [0.9-1.9] for major bleeding. Event rates were stable over the 3 study years. Placebo patients in the PEGASUS-TIMI54 Study were younger, more often male and had lower event rates, especially for all-cause death and major bleeding. CONCLUSIONS: Patients selected using the criteria described in PEGASUS were older with more comorbidities, resulting in higher all-cause death and bleeding rates, but similar MI recurrence rates.

Persistence to 5-year hormonal breast cancer therapy: a French national population-based study.

BACKGROUND: Non-persistence to oral hormonal therapy (HT) in breast cancer (BC) is an emerging health issue, and estimations vary according to the population selected and/or the statistical method applied. This study aimed to estimate non-persistence over 5 years to HT in an unselected sample of women with BC using a French national population-based database and accounting for competing risks. METHODS: A retrospective cohort of 600 women initiating a HT between 2006 and 2007 was constituted using a representative sample of the French national healthcare insurance system database. The Cumulative Incidence Function method was used to estimate the probability of first treatment discontinuation of at least 90 days accounting for competing risk of death from any cause over the theoretical 5-year period of treatment. RESULTS: Thirty one percent of patients who initiated a HT were identified as non-persistent at the fifth year of follow-up. Patients who switched to another HT (HR 3.10, 95% CI (2.20; 4.36)) or had metastatic BC (HR 3.07, 95% CI (1.73; 5.46)) were more likely to be non-persistent. Women who initiated aromatase inhibitors as compared with tamoxifen (HR 0.62, 95% CI (0.46; 0.83)), had administrative registration for BC (HR 0.21, 95% CI (0.13; 0.32)), or had received an adjuvant chemotherapy (HR 0.65, 95% CI (0.48; 0.89)) were less likely to discontinue. CONCLUSIONS: The estimate of long-term non-persistence in an unselected sample of women treated in France by oral hormonal therapy is substantial, even accounting for competing risks.

Liver transplant associated with paracetamol overdose: results from the seven-country SALT study.

AIMS: Acute drug overdose, especially with paracetamol, may cause acute liver failure leading to registration for transplantation (ALFT). Population statistics and between-country differences for ALFT related to overdose have been poorly described. The aim of the present study was to evaluate overdose ALFT in the multi-country Study of Acute Liver Transplantation (SALT). METHODS: All adult overdose-related ALFT, with or without suicidal intent, in France, Greece, Ireland, Italy, the Netherlands, Portugal and the UK between 2005 and 2007 were identified from liver transplant registries and hospital records. These were compared with whole-country and per capita use of paracetamol. RESULTS: Six hundred cases of ALFT were identified in 52 of 57 eligible transplant centres, of which 114 involved overdose (72 intentional, 10 non-intentional, 32 uncertain). Overdose represented 20% of all-cause ALFT: Ireland 52%, UK 28%, France 18%, the Netherlands 8%, and Italy 1%. Overdose ALFT were mostly females (61%), mean age 33.6 ± 10.9 years. A total of 111 (97%) of the overdoses involved paracetamol. Event rates ranged from one ALFT for 20.7 tons of paracetamol in Ireland, to one for 1074 tons in Italy and one case in 60 million inhabitants over 3 years in Italy to one case in 286 000 inhabitants per year in Ireland. Per-country event rates for non-overdose ALFT exposed to paracetamol were between 2.5 and 4.0 per million treatment-years sold. CONCLUSIONS: Paracetamol overdose was found to represent one-sixth of all-cause ALFT. There was a 50-fold difference in Europe in the rates of paracetamol overdose ALFT, and a 200-fold difference per million inhabitants.

Choice of the denominator in case population studies: event rates for registration for liver transplantation after exposure to NSAIDs in the SALT study in France.

PURPOSE: The effect of denominator options on event rates was tested on the French part of the Study of Acute Liver Transplant (SALT). METHODS: SALT is a case population study of acute liver failure registered for transplantation (ALFT), exposed to non-steroidal anti-inflammatory drugs (NSAIDs) or non-overdose paracetamol, from 2005 to 2007. Population exposure was computed from the Intercontinental Medical Services' (IMS) and the French national healthcare insurance system's data as the number of defined daily doses (DDDs) sold or dispensed and the number of exposed patients. RESULTS: Nine ALFT cases were exposed to 10 NSAIDs and 49 to non-overdose paracetamol. NSAID sales ranged from 0.04 billion (niflumic acid) to 0.5 billion (ibuprofen) DDDs, amounting to 2.5 billion DDDs for all NSAIDs. The mean per-person exposure ranged from 13.1 (niflumic acid) to 43.2 (ketoprofen) DDDs, reaching 60.5 DDDs for any NSAID. The number of users ranged from 2 million (niflumic acid) to 13 million (ibuprofen), which was 26.6 million for all NSAIDs. The ALFT rates per billion DDDs ranged from 0 to 26 for individual NSAIDs and amounted to 4.6 for all NSAIDs. The ALFT rates per billion DDDs were inversely correlated with the average per-patient exposure (R(2) = 0.935, p = 0.0016). The ALFT rates per million users ranged from 0.31 to 0.49, which was 0.41 for all NSAIDs, with no difference between drugs and no effect of mean per-patient exposure (R(2) = 0.01, p = 0.9). Whether measured per DDD or per user, the event rate with paracetamol was three to five times higher than with NSAIDs. CONCLUSION: ALFT risk with NSAID seems to be user dependent rather than person-time (exposure) dependent. Choosing the wrong denominator in case population studies might give erroneous results.

Impact of Cardiovascular Comorbidities on the Effectiveness and Safety of Bevacizumab in Older Patients with Metastatic Colorectal Cancer.

BACKGROUND: Cardiovascular comorbidities are not contraindications of bevacizumab for metastatic colorectal cancer. OBJECTIVE: We aimed to evaluate the impact of cardiovascular comorbidities before bevacizumab treatment on overall survival and cardiovascular safety in older patients with metastatic colorectal cancer. METHODS: A 2009-2015 cohort of patients with metastatic colorectal cancer aged ≥ 65 years administered first-line bevacizumab was extracted from the French healthcare reimbursement claims database. Baseline heart failure, hypertension, and venous/arterial thromboembolic events were identified. The 36-month overall survival rate was evaluated using the Kaplan-Meier method, and the impact of cardiovascular comorbidities on the 36-month overall survival using a time-dependent, multivariable, Cox proportional hazards model. The 36-month cumulative incidence of cardiovascular events, and the impact of cardiovascular comorbidities on the likelihood of cardiovascular events were evaluated using the Fine and Gray model, with death as a competing risk. RESULTS: We included 9222 patients (56.4% male; median age 73 years). Two-thirds (66.7%) had baseline cardiovascular comorbidities. The median 36-month overall survival was 20.4 [95% confidence interval (CI) 19.9-21.0] and 21.8 [95% CI 21.1-22.6] months in patients with and without cardiovascular comorbidities, respectively. Age ≥ 75 years, dependency in activities of daily living, radiotherapy, and another targeted therapy were identified as death risk factors, but not cardiovascular comorbidities. At 36 months, cardiovascular events had occurred in 60.2% [95% CI 58.9-61.4] and 44.1% [95% CI 42.3-45.9] of patients with and without cardiovascular comorbidities. Baseline venous thrombosis, female, three or more cardiovascular medications, another targeted therapy, and more than six bevacizumab injections were identified as risk factors for cardiovascular events. CONCLUSIONS: In clinical practice, cardiovascular comorbidities before administering bevacizumab to older patients with metastatic colorectal cancer impacted the cardiovascular safety, but not overall survival. Unless they limit functional independency, older patients with cardiovascular comorbidities should be treated with bevacizumab under close monitoring.

Strong instrumental variables biased propensity scores in comparative effectiveness research: A case study in oncology.

BACKGROUND AND OBJECTIVES: Some medications require specific medical procedures in the weeks before their start. Such procedures may meet the definition of instrumental variables (IVs). We examined how they may influence treatment effect estimation in propensity score (PS)-adjusted comparative studies, and how to remedy. STUDY DESIGN AND SETTING: Different covariate assessment periods (CAPs) did and did not include the month preceding treatment start were used to compute PS in the French claims database (Sytème National des Données de Santé-SNDS), and 1:1 match patients with metastatic castration resistant prostate cancer initiating abiraterone acetate or docetaxel. The 36-month survival was assessed. RESULTS: Among 1, 213 docetaxel and 2, 442 abiraterone initiators, the PS distribution resulting from the CAP [-12; 0 months] distinctly separated populations (c = 0.93; 273 matched pairs). The CAPs [-12;-1 months] identified 765 pairs (c = 0.81). Strong docetaxel treatment predictors during the month before treatment start were implantable delivery systems (1% vs. 59%), which fulfilled IV conditions. The 36-month survival was not meaningfully different under the [-12; 0 months] CAP but differed by 10% points (38% vs. 28%) after excluding month -1. CONCLUSION: In the setting of highly predictive pretreatment procedures, excluding the immediate pre-exposure time from the CAP will reduce the risk of including potential IVs in PS models and may reduce bias.

Clustering of prostate cancer healthcare pathways in the French National Healthcare database.

Background: Healthcare pathways of patients with prostate cancer are heterogeneous and complex to apprehend using traditional descriptive statistics. Clustering and visualization methods can enhance their characterization. Methods: Patients with prostate cancer in 2014 were identified in the French National Healthcare database (Système National des Données de Santé-SNDS) and their data were extracted with up to 5 years of history and 4 years of follow-up. Fifty-one-specific encounters constitutive of prostate cancer management were synthesized into four macro-variables using a clustering approach. Their values over patient follow-ups constituted healthcare pathways. Optimal matching was applied to calculate distances between pathways. Partitioning around medoids was then used to define consistent groups across four exclusive cohorts of incident prostate cancer patients: Hormone-sensitive (HSPC), metastatic hormone-sensitive (mHSPC), castration-resistant (CRPC), and metastatic castration-resistant (mCRPC). Index plots were used to represent pathways clusters. Results: The repartition of macro-variables values-surveillance, local treatment, androgenic deprivation, and advanced treatment-appeared to be consistent with prostate cancer status. Two to five clusters of healthcare pathways were observed in each of the different cohorts, corresponding for most of them to relevant clinical patterns, although some heterogeneity remained. For instance, clustering allowed to distinguish patients undergoing active surveillance, or treated according to cancer progression risk in HSPC, and patients receiving treatment for potentially curative or palliative purposes in mHSPC and mCRPC. Conclusion: Visualization methods combined with a clustering approach enabled the identification of clinically relevant patterns of prostate cancer management. Characterization of these care pathways is an essential element for the comprehension and the robust assessment of healthcare technology effectiveness.

Seizure freedom is not adversely affected by early discontinuation of concomitant anti-epileptic drugs in the EULEV cohort of levetiracetam users.

PURPOSE: Fear of discontinuing concomitant anti-epileptic drugs (AEDs) may lead to potentially unnecessary and perhaps unsafe polypharmacy. The effect of withdrawing concomitant AEDs on epilepsy control was therefore studied in long-term users of levetiracetam. METHODS: The EULEV cohort followed patients initiating levetiracetam in France in 2005 or 2006 for one year. In those maintaining levetiracetam throughout the study period, the association of a reduction in the number of concomitant AEDs during the first six months with seizure-freedom during the last six months of follow-up was investigated using logistic regression. RESULTS: Of the 356 patients continuing levetiracetam for at least 1 year, 140 (39.3%) were seizure-free during the last six months of follow-up. Partial symptomatic or generalised idiopathic epilepsy were associated with greater seizure-freedom than partial cryptogenic disease. Factors associated with seizures were: longer disease duration, initial incapacity, increased number of seizures in the six months preceding levetiracetam initiation, and number of consultations for epilepsy in the six months preceding levetiracetam initiation. There was a trend for the association between the early reduction in the number of concomitant AEDs and seizure-free status later during follow-up, which however did not reach statistical significance in the final propensity score-adjusted multivariate model (OR = 1.8, 95%CI [0.8;4.0]). CONCLUSIONS: Taking into account the various risk factors for seizures, the early reduction of concomitant AEDs was not associated with worse seizure rates during follow-up in real-life users of levetiracetam.

Abiraterone acetate versus docetaxel for metastatic castration-resistant prostate cancer: a cohort study within the French nationwide claims database.

OBJECTIVES: To conduct the direct comparison of abiraterone acetate and docetaxel for first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-life settings. METHODS: Data were extracted from the French nationwide claims database (SNDS) on all men aged ≥40 years starting first-line treatment with abiraterone acetate or docetaxel for mCRPC in 2014. A high-dimensional propensity score including 100 baseline characteristics was used to match patients of both groups and form two comparative cohorts. Three-year overall survival and treatment discontinuation-free survival were determined using Kaplan-Meier analysis. RESULTS: In 2014, 2,444 patients started abiraterone for treatment of mCRPC and 1,214 started docetaxel. After trimming and matching, 716 patients were available in each group. Median overall survival tended to be longer in the abiraterone acetate cohort (23.8 months, 95% confidence interval = [21.5; 26.0]) than in the docetaxel cohort (20.3 [18.4; 21.6] months). Survival at 36 months was 34.6% for abiraterone acetate and 27.9% for docetaxel (p = 0.0027). Treatment discontinuation-free median was longer in the abiraterone acetate cohort compared to the docetaxel cohort (10.8 [10.1; 11.7] versus 7.4 [7.0; 8.0] months). CONCLUSION: The findings underline the interest of oral abiraterone acetate over intravenous docetaxel as the first-line treatment option in mCRPC.

The EULEV cohort study: rates of and factors associated with continuation of levetiracetam after 1 year.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Levetiracetam has shown good safety/tolerability and efficacy in regulatory trials. This was confirmed in observational investigations performed soon after marketing by using continuation or retention rates as a composite measure. When an anti-epileptic drug first becomes available; however, there is evidence of channelling to more severe patients than thereafter. WHAT THIS STUDY ADDS: This study was performed several years after marketing of levetiracetam and found high rates of continuation. It also further explores this measure by determining the continuation in the absence of initiation of additional anti-epileptic drugs. AIMS: To investigate real-life effectiveness of levetiracetam in patients initiating treatment in a stable market situation. METHODS: Epileptic adults who had initiated levetiracetam between 1 January and 31 August in 2005 or 2006 were included and followed for 1 year by hospital or nonhospital neurologists practising in France. One-year continuation rates were estimated using Kaplan-Meier analysis. Among those still treated at end of study, treatment goals were investigated. Factors associated with discontinuation were investigated using Cox proportional hazards regression. RESULTS: A total of 794 subjects were included in the cohort, and 753 subjects were followed up and included in the analysis. Among these, mean (SD) age was 42.6 (±17.0) years, 51.1% were female, 76.6% had partial epilepsy, 93.5% had seizures in the 6 months preceding levetiracetam initiation and 82.9% had at least one concomitant anti-epileptic drug when starting levetiracetam. One-year levetiracetam continuation rate was 83.5% (95% confidence interval, 80.5-86.0%). Of the 579 patients still using levetiracetam at end of study, 46.8% were seizure free during the last 6 months, and 24% were on levetiracetam monotherapy. Reasons for discontinuation (n= 122) were adverse events (45%), lack of efficacy (38%) or both (9%). Levetiracetam discontinuation was most strongly associated with previous exposure to more than four anti-epileptic drugs, whereas continuation was most strongly associated with presence of seizure-related falls in the 6 months preceding levetiracetam initiation. CONCLUSIONS: This population-based cohort study in a stable market situation found a high 1 year levetiracetam continuation rate compared with previous studies done sooner after market introduction.

Secondary prevention of acute coronary syndrome with antiplatelet agents in real life: A high-dimensional propensity score matched cohort study in the French National claims database.

Users of newly marketed drugs often differ from the patients included in randomized clinical trials, and from patients prescribed similar drugs. Cohorts of such users may be compared using propensity score adjustment, or similar user cohorts may be built using high-dimensional propensity score matching in large population databases. One such database is SNDS, the French nationwide claims and hospitalization database, which covers 99 % of the French population. It has yet been rarely used. To study the comparative effectiveness and safety in secondary coronary prevention of ticagrelor, compared to clopidogrel or prasugrel, we identified in SNDS patients who were dispensed any of the three antiplatelet agents of interest (± aspirin) within a month after discharge from hospital for acute coronary syndrome (ACS) and followed them one year for recurrence of ACS, stroke, acute bleeding, or death. High-dimensional propensity scores were developed to identify matched cohorts. Drug performances were also compared in the whole population using adjustment on the same parameters. Here we describe the database that was used, and the methods developed for the high-dimensional propensity score matching, resulting in standardized mean differences between the matched populations of less than 2 % for all of the 500+ variables included in the model. •This study was done in a newly available large-scale claims database, which may differ from other population databases, by it size and exhaustiveness•The methods elaborate on standard high-dimensional propensity scores as adapted to this claims database.

Quality of Life and Pain During Treatment of Metastatic Castration-resistant Prostate Cancer With Cabazitaxel In Routine Clinical Practice.

BACKGROUND: This prospective study collected quality of life (QoL) and pain data during cabazitaxel treatment in patients with advanced metastatic or castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Functional Assessment of Cancer Therapy-Prostate (QoL) and Brief Pain Inventory-Short Form (pain) questionnaires were collected over 6 months. RESULTS: In 61 patients with mCRPC (median age, 72 years) from 22 centers, metastatic sites were bones (97%), lymph nodes (36%), and visceral (20%); 25% received cabazitaxel in the second line, 29% in the third line, and 46% in the fourth line or beyond. All had been previously treated with docetaxel, except one with paclitaxel, and 75% also with abiraterone, enzalutamide, or both. The median cabazitaxel duration was 3.4 months. Forty-nine patients were evaluable for QoL and 44 for pain. QoL was improved in 37%, maintained in 35%, and deteriorated in 37%. In 27%, pain decreased ≥ 1 level and remained stable in 52%. A total of 34% lowered analgesic drug level. Prostate-specific antigen response ≥ 50% was observed in 11 (32.6%) patients, of whom 7 improved QoL and 1 was stable. At 6 months, 83.6% survived (95% confidence interval, 71.7%-90.8%). A total of 46% had ≥ 1 grade ≥ 3 adverse events, mainly anemia and neutropenia. CONCLUSION: Although cabazitaxel was given as the third line and beyond for three-quarters of patients, over one-third had improved QoL and/or decreased pain during treatment.

Epidemiology of metastatic castration-resistant prostate cancer: A first estimate of incidence and prevalence using the French nationwide healthcare database.

BACKGROUND: There is a lack of information about the burden of metastatic castration-resistant prostate cancer (mCRPC). The present work aims to estimate the incidence and prevalence of mCRPC in 2014 using the French nationwide healthcare database (SNDS). METHODS: Prevalence and incidence were estimated based on an SNDS extraction of men covered by the general healthcare insurance (86 % of the French population), and aged ≥40. Patients with mCRPC were identified amongst prostate cancer cases using an algorithm estimating a date of first metastasis management and a date of castration resistance. This algorithm was validated by clinical experts through a blind review of 200 anonymized medical charts from SNDS data. Prevalence and incidence were standardized on the European Standard Population (2013 edition). RESULTS: Prevalence and incidence of mCRPC were estimated as, respectively, 62 and 21 cases per 100 000 men in 2014. Less than one mCRPC case per 100 000 was observed in men aged 40-49. Maximum mCRPC incidence was in men aged 80-89 (175 per 100 000). The algorithm used for mCRPC identification had 97 % positive and 99 % negative predictive values. CONCLUSION: The good performances of the algorithm for mCRPC identification and the consistency of the generated results with the existing data highlight the robustness of these first estimates of mCRPC prevalence and incidence. Future updates will call for algorithm adjustment as practices evolve over time. These first real-life data will serve for future follow-up of the impact of changes in the management of prostate cancer.

Treatment Modalities and Survival in Older Adults with Metastatic Colorectal Cancer in Real Life.

OBJECTIVES: Metastatic colorectal cancer (mCRC) is increasingly treated with targeted therapies, but little is known about real-life mCRC treatment in older adults. The aims were to describe the real-life first-line treatment modalities in older adult mCRC patients, to identify factors associated with treatment modalities, and to evaluate survival with regard to treatment modalities. PATIENTS AND METHODS: A cohort of mCRC patients aged 65 years and older at diagnosis was identified between 2009 and 2013 using French national healthcare insurance system claims data. Treatment modalities were: treatment with one or more anticancer medication vs best supportive care and, among treated patients, treatment with targeted therapy vs conventional chemotherapy alone. Multivariate logistic regression was used to identify factors associated with treatment by anticancer medication and by targeted therapy. Cox proportional hazards models were used to assess the independent effect of treatment modalities on overall survival while adjusting for baseline covariates identified with logistic regression. RESULTS: A total of 503 patients were included with a median age of 78 years (54% were men). Of these, 299 (59%) were treated with anticancer medications. Among treated patients, 131 (44%) received targeted therapy. In multivariate analysis, age 75 years or older, renal failure, malnutrition, and five or more concomitant medications were associated with a lower likelihood of treatment with anticancer medications. Among treated patients, age 75 years or older, history of cancer, lymph node metastases, and a single metastatic site were associated with a lower likelihood of treatment with targeted therapy. Multivariate Cox proportional hazards models found that treatment with any anticancer medication tended to be associated with a lower risk of death; treatment with targeted therapy was not significantly associated. CONCLUSION: A more appropriate prescription of anticancer medications in the older adult will require the definition of more explicit criteria to avoid undertreatment. The real benefit of targeted therapies vs conventional chemotherapy alone needs to be confirmed in this population. J Am Geriatr Soc 67:913-919, 2019.