Neurocognitive Disorders Associated with PCSK9 Inhibitors: a Pharmacovigilance Disproportionality Analysis.

PURPOSE: PCSK9 might affect central nervous system development, neuronal apoptosis, and differentiation. We investigate the neurocognitive adverse events associated with the use of PCSK9 inhibitors (alirocumab and evolocumab) using pharmacovigilance reports. METHODS: We used the World Health Organization pharmacovigilance database (VigiBase) to perform a disproportionality analysis comparing the proportion of neurocognitive adverse events reported with PCSK9 inhibitors versus the proportion of these effects reported since August 14, 2015 (date of first post-marketing report suspecting a PCSK9 inhibitor), for all drugs in the database. Associations between PCSK9 inhibitor use and neurocognitive adverse events were assessed using both proportional reporting ratio (PRR) and information component (IC). Complementary analyses were performed on other neurologic events, and different sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: Among the 81,108 reports involving at least one PCSK9 inhibitor, 1,941 concerned the occurrence of neurocognitive disorders. Most of patients (52.3%) were aged 45-74 years, and 58.0% were women. Signals of disproportionate reporting were found for PCSK9 inhibitors (PRR 1.22, 95% CI 1.17; 1.28; IC 0.28, IC025 0.21) and for each drug individually. No signal of disproportionality was found for any of the other neurologic events investigated. Signals of disproportionate reporting were found for the positive control (benzodiazepines), but not for the negative control (aspirin). The results of the main analysis were confirmed by sensitivity analyses. CONCLUSIONS: This study identified a signal of neurocognitive disorders associated with PCSK9 inhibitors and encourages paying attention to at-risk populations.

JAK inhibitors and risk of major cardiovascular events or venous thromboembolism: a self-controlled case series study.

PURPOSE: JAK-inhibitors (JAK-i) might be associated with venous (VTE) and arterial thromboembolic events (ATE). To evaluate the association between JAK-i and the risk of VTE and ATE. METHODS: A self-controlled case series was performed using data from the nationwide French healthcare insurance system database SNDS. We included all patients treated with JAK-i (baricitinib or tofacitinib), and having presented at least one VTE or ATE between November 1, 2017 and June 30, 2019. Associations were estimated using the incident rate ratio (IRR). Two post-exposure periods (until day 30 and until day 60) were individualized. RESULTS: Among 5870 patients with JAK-i dispensing, 92 had an incident VTE or ATE within the study period. Their median age at JAK-i initiation was 65.7 years [IQR: 56.1-75.8] and 65.2% were female (n = 60). Before event incidence, 65.2% (n = 60) received baricitinib, 32.6% (n = 30) tofacitinib and 2.2% (n = 2) had both medications. Moreover, 41.3% (n = 38) presented a VTE and 58.7% (n = 54) an ATE. The median time-to-onset after JAK-i initiation was 4.6 months [IQR: 2.5-9.2] for VTE and 6.1 months [IQR: 3.0-8.5] for ATE. An IRR of 8.27 (95% CI 3.41-20.04) for VTE was detected during JAK-i treatment and remained increased over the 30-day period of post-exposure (6.52 [2.02-21.11]). An IRR of 9.27 (3.68-23.34) was also found for ATE, which remained increased over the 30-day period of post-exposure (10.12 [3.27-31.37]). No increased risk was detected during long-term post-exposure for either VTE or ATE. CONCLUSIONS: This study shows evidence of an increased risk of VTE and ATE associated with the use of baricitinib and tofacitinib.

A safety signal of somnambulism with the use of antipsychotics and lithium: A pharmacovigilance disproportionality analysis.

AIMS: Antipsychotics and lithium are widely used in psychiatry, particularly in schizophrenia and bipolar disorders. Recently, some cases of somnambulism or sleep-related eating disorder (SRED) have been reported in patients treated with these drugs. This study investigated the risk of reporting somnambulism or SRED associated with the use of antipsychotics and lithium. METHODS: The World Health Organization pharmacovigilance database (VigiBase), comprising >18 million adverse events, was queried. All somnambulism or SRED reports related to antipsychotics or lithium were identified. The association between antipsychotics or lithium and somnambulism or SRED was computed using the proportional reporting ratio (PRR) and information component. RESULTS: Among the 5784 cases reporting somnambulism or SRED, 508 suspected at least 1 antipsychotic or lithium. Most patients were aged 18-64 years (62.0%), and 37.0% were men. In most cases (77.6%), antipsychotic or lithium were the only drug class involved, and 53.3% of cases suspected quetiapine. Somnambulism was reported in 88.6% of cases and SRED in 18.1%. A significant association was found for second-generation antipsychotics (PRR 3.44, 95% confidence interval 3.13) and lithium (PRR 2.03, [1.22; 3.37]), but not for first-generation antipsychotics (PRR 0.99, [0.68; 1.44]). CONCLUSIONS: We found a significant signal of somnambulism or SRED related to second-generation antipsychotics and lithium. While case reports mentioned mostly quetiapine and olanzapine, almost all second-generation antipsychotics were associated with somnambulism or SRED.

Adverse events reported for Mirena levonorgestrel-releasing intrauterine device in France and impact of media coverage.

AIMS: In 2017, concerns regarding adverse events (AEs) associated with the Mirena levonorgestrel intrauterine device were largely echoed in the media in France. This resulted in a tremendous reporting of AEs to pharmacovigilance centres. The aim of this study was to describe the reporting of AEs regarding Mirena in France and to study the impact of media coverage on this reporting. METHODS: All cases reports involving Mirena recorded in the French national pharmacovigilance database from marketing (21 July 1995) until 04 August 2017 were extracted. To allow studying the influence of mediatisation, reports were described separately for the periods preceding and following the observed media coverage peak (15 May 2017). RESULTS: Overall, 3224 reports were considered, 510 (15.8%) recorded before the media coverage peak, and 2714 (84.2%) after. Before the peak, 76.5% of reports originated from health professionals; median time-to-report was of 5.5 months (interquartile range: 1.7-18.6), and median number of AEs per report was 1 (range: 1-17). After the peak, 98.6% originated from patients; median time-to-report was 21 months (interquartile range: 8.1-45.5), and median number of AEs per report was 6 (range: 1-37). After the peak, most reports mentioned anxio-depressive disorders (38.8 vs 10.6% before) or sexual disorders (47.3 vs 6.9%). Other emphasised AEs were weight increase (42.3 vs 10.2%) and pain (gastrointestinal, 19.1 vs 3.5%; musculoskeletal, 22.2 vs 4.5%). CONCLUSION: This study highlighted the importance of mediatisation impact on spontaneous reporting with changes concerning amounts of reports, type of reporter, and type of reported AEs. For Mirena, this led to generate signals regarding anxio-depressive and sexual disorders.

National trends in use and costs of oral anticancer drugs in France: An 8-year population-based study.

PURPOSE: During the last decade, many oral anticancer drugs (OAcDs) have been marketed, providing interesting but potentially costly pharmaceutical alternatives to intravenous treatments. This study aims to provide updated information on their use and costs. METHODS: A cross-sectional yearly repeated study was conducted from 2006 to 2014 using the representative sample of the French national health care insurance system claims database (EGB). OAcD use was described for each year, among prevalent (ie, patients with at least 1 OAcD reimbursement) and incident users (ie, patients with no OAcD reimbursement within the prior year) and according to their pharmacological classes (Hormone Therapy [HT], Cytotoxic Therapy [CT], Targeted Therapy [TT], and others). Demographic characteristics were described for both users; comorbidities and direct medical costs were described for incident users only. RESULTS: The yearly prevalence and incidence of OAcD use, mainly represented by HT, remained stable from 2006 to 2014 (1.2%; 0.4%). Compared with users of other OAcD classes, the proportion of TT users substantially increased over the 8-year study period (+9.3%), and TT incident users had more severe comorbidities at treatment initiation. The health expenditures were the most important in TT users with median monthly medical direct costs varying from 2995€ to 4968€ per patient between 2006 and 2014. CONCLUSION: With the development of new OAcDs, the TTs use reaches a wider population of patients but is responsible for increasing health expenditures.

[Not Available]. / Comment le grand public utilise Internet pour rechercher des informations sur le médicament ?

UNLABELLED: To quantify and characterize the use of the Internet to search for information about medicines. METHODS: A random sample of subjects was interviewed in the city of Bordeaux (France) in November 2012 regarding their use of the Internet to find information on medicines. RESULTS: Among 103 interviewed subjects (median age: 38years; 53.4% of men), 48 (46.6%) reported using the Internet to find information about medicines (58.3% of women). Two-thirds (66.7%) declared visiting consumer forums. However, nearly 60% reported to first consult a health professional. Three subjects had already bought medicines on the web and half (52.0%) of those who never made a purchase on the Internet would not trust the quality of the medicine. CONCLUSION: Even if purchasing medicines on the web remains rare, this media is frequently used to find information on medicines and most often on websites of questionable quality.

[How people use the internet to find information on medicines?]. / Comment le grand public utilise Internet pour rechercher des informations sur le médicament ?

OBJECTIVE: To quantify and characterize the use of the Internet to search for information about medicines. METHODS: A random sample of subjects was interviewed in the city of Bordeaux (France) in November 2012 regarding their use of the Internet to find information on medicines. RESULTS: Among 103 interviewed subjects (median age: 38 years; 53.4% of men), 48 (46.6%) reported using the Internet to find information about medicines (58.3% of women). Two-thirds (66.7%) declared visiting consumer forums. However, nearly 60% reported to first consult a health professional. Three subjects had already bought medicines on the web and half (52.0%) of those who never made a purchase on the Internet would not trust the quality of the medicine. CONCLUSION: Even if purchasing medicines on the web remains rare, this media is frequently used to find information on medicines and most often on websites of questionable quality.

Real-World Treatment Patterns and Effectiveness of Patients With Advanced Renal Cell Carcinoma: A Nationwide Observational Study.

BACKGROUND: Treatment landscape for advanced renal cell carcinoma (aRCC) has evolved quickly and few data about the real-world treatment patterns are available. This study aimed at describing the real-world treatment patterns and effectiveness of all systemic treatments available for aRCC in first and second-line treatment. MATERIALS AND METHODS: A cohort of patients initiating a first-line systemic treatment for aRCC in 2016 was extracted from the French nationwide healthcare insurance system database (SNDS). The first-line treatment initiation date constituted the index date and patients were followed until death, loss to follow-up, or December 31, 2019, whichever occurred first. aRCC was identified using hospital diagnosis, long-term disease, or renal biopsy before index date. All analyses were performed for first and second-line treatment. Overall survival (OS) and time-to-next treatment or death (TNT-D) were estimated using Kaplan-Meier approach. RESULTS: In 2016, 1629 patients initiated a first-line treatment for aRCC. Most of them were male (75.9%) and the median age was 67 years. Most of patients (91.7%) had received a tyrosine kinase inhibitor as first-line treatment, mainly sunitinib (64.4%), and 53.5% received a second-line, among which 43.7% nivolumab. Median OS (95% confidence interval [CI]) was 20.7 (95% CI:18.2-22.4) months from first-line treatment initiation and 15.4 (13.9-17.5) months from second-line treatment initiation. Median TNT-D were respectively 9.3 (9.7-12.1) months and 6.9 (5.9-7.7) months. CONCLUSION: This study highlights the limited survival of aRCC patients These results provide a valuable baseline and highlight the need for innovation, such as immune checkpoint inhibitor-based combinations that have recently became first-line standard of care.

Impact of liquid sublingual immunotherapy on asthma onset and progression in patients with allergic rhinitis: a nationwide population-based study (EfficAPSI study).

Background: The only disease-modifying treatment currently available for allergic rhinitis (AR) is allergen immunotherapy (AIT). The main objective of the EfficAPSI real-world study (RWS) was to evaluate the impact of liquid sublingual immunotherapy (SLIT-liquid) on asthma onset and evolution in AR patients. Methods: An analysis with propensity score weighting was performed using the EfficAPSI cohort, comparing patients dispensed SLIT-liquid with patients dispensed AR symptomatic medication with no history of AIT (controls). Index date corresponded to the first dispensation of either treatment. The sensitive definition of asthma event considered the first asthma drug dispensation, hospitalisation or long-term disease (LTD) for asthma, the specific one omitted drug dispensation and the combined one considered omalizumab or three ICS ± LABA dispensation, hospitalisation or LTD. In patients with pre-existing asthma, the GINA treatment step-up evolution was analysed. Findings: In this cohort including 112,492 SLIT-liquid and 333,082 controls, SLIT-liquid exposure was associated with a significant lower risk of asthma onset vs. control, according to all definitions (combined: HR [95% CI] = 0.62 [0.60-0.63], sensitive: 0.77 [0.76-0.78], and specific: 0.67 [0.61-0.72]). Exposure to SLIT was associated with a one-third reduction in GINA step-up regardless baseline steps. Interpretation: In this national RWS with the largest number of person-years of follow-up to date in the field of AIT, SLIT-liquid was associated with a significant reduction in the risk of asthma onset or worsening. The use of three definitions (sensitive or specific) and GINA step-up reinforced the rigorous methodology, substantiating SLIT-liquid evidence as a causal treatment option for patients with respiratory allergies. Funding: Stallergenes Greer.

A successful linkage of a named patient products of sublingual immunotherapy-dispensing registry to French healthcare insurance database (SNDS): methodological constitution of the EfficAPSI cohort.

BACKGROUND: The only causal treatment for allergic rhinitis (AR) is allergen immunotherapy (AIT) including personalized liquid sublingual AIT (SLIT). We present the methodology for establishing the EfficAPSI cohort to further evaluate the real-life effectiveness and use of SLIT liquid. RESEARCH DESIGN AND METHODS: The EfficAPSI cohort was constituted by deterministic linkage of Stallergenes Greer dispensing and nationwide French healthcare insurance system (SNDS) databases. Data from 2006 to 2018 were extracted. All patients who initiated Stallergenes Greer SLIT liquid between 2010 and 2013 were considered as exposed and those dispensed with AR symptomatic treatment only as control. To limit the impact of confounding, the models will be weighted using the inverse probability of treatment weighting (IPTW). RESULTS: A total of 445,574 patients were included; median age was 38 years; 59.1% were female. Exposed patients (n = 112,492) were significantly younger, more frequently males, and less likely to have comorbidities than controls (n = 333,082). After IPTW, patients' characteristics from both groups were similar. CONCLUSIONS: To date, the EfficAPSI cohort has the largest number of person-years of follow-up in the field of AIT. The completeness of the data allows to evaluate SLIT liquid effectiveness with rigorous methodology, leading to important insights on personalized medicine in real-life.

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.

GLP-1 Receptor Agonists and the Risk of Thyroid Cancer.

OBJECTIVE: To determine whether use of glucagon-like peptide 1 (GLP-1) receptor agonists (RA) is associated with increased risk of thyroid cancer. RESEARCH DESIGN AND METHODS: A nested case-control analysis was performed with use of the French national health care insurance system (SNDS) database. Individuals with type 2 diabetes treated with second-line antidiabetes drugs between 2006 and 2018 were included in the cohort. All thyroid cancers were identified through hospital discharge diagnoses and medical procedures between 2014 and 2018. Exposure to GLP-1 RA was measured within the 6 years preceding a 6-month lag-time period and considered as current use and cumulative duration of use based on defined daily dose (≤1, 1 to 3, >3 years). Case subjects were matched with up to 20 control subjects on age, sex, and length of diabetes with the risk-set sampling procedure. Risk of thyroid cancer related to use of GLP-1 RA was estimated with a conditional logistic regression with adjustment for goiter, hypothyroidism, hyperthyroidism, other antidiabetes drugs, and social deprivation index. RESULTS: A total of 2,562 case subjects with thyroid cancers were included in the study and matched with 45,184 control subjects. Use of GLP-1 RA for 1-3 years was associated with increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27-1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04-3.05). CONCLUSIONS: In the current study we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1-3 years of treatment.

Clinical impact of STK11 mutation in advanced-stage non-small cell lung cancer.

BACKGROUND: Mutations in STK11/LKB1 gene present a negative impact on tumour immune microenvironment, especially with concomitant activating KRAS mutation. These recent data may explain a decreased response to immunotherapy treatment in STK11 mutant non-small cell lung cancer (NSCLC). OBJECTIVE: The primary objective is to evaluate, in a real-life setting, overall survival (OS) in patients with NSCLC according to the presence of STK11 mutation. The secondary objective is to assess time to treatment failure (TTF) for the first-line chemotherapy or immunotherapy. METHODS: This observational multicentric study was conducted in Nouvelle-Aquitaine (France), for 24 months. Clinical, histopathological and imagery data were collected in each centre while the next-generation sequencing analysis was performed in Bordeaux Hospital University. Patient's data were longitudinally followed from NSCLC diagnosis date to the occurrence of censoring events (therapeutic failure or death, as applicable) or until the study end date. RESULTS: median OS from the first drug administration was significantly longer for STK11wt patients than STK11mut patients (16.2 months [11 - nr] versus 4.7 months [2.5-9.4]; Log-rank test P < 0.001). The Presence of STK11 mutation was significantly associated with shortened OS (RR = 2.26 [1.35-3.79], P = 0.002). First-line TTF was significantly shorter in STK11mut population and the presence of the mutation was significantly associated with an increase in treatment failures (RR = 1.87 [1.21-2.89], P = 0.005). The type of treatment (chemotherapy, immunotherapy) does not influence the amplitude of reduced TTF in patients with STK11mut. CONCLUSION: The presence of STK11 mutation is associated with poor prognosis in NSCLC.

Overview of French databases available for studying anticancer drugs in real-life setting.

Considering their novelty and cost, post-marketing evaluation is highly relevant for new anticancer drugs. Identify and characterize available and potentially useful databases for post-marketing evaluation of these specific drugs is necessary. A review was conducted to identify available and accessible databases to study the post-marketing evaluation of drugs in real-life care setting. Databases identified have been classified into medico-administrative databases, medical record databases, and databases resulting from ad hoc collections. Taking as examples databases available in France, each type was described as well as its strengths and limits for a potential use in the oncology field. Record linkage of medico-administrative databases could cover almost the whole population and is now used to evaluate anticancer drugs (e.g., Système National des Données de Santé). Large medical record databases are still lacking, but efforts are currently made to give access to hospital data warehouses for research purposes. Finally, databases resulting from ad hoc collections are also available for some cancer localizations and allow to obtain highly valuable clinical and biological data. A range of important and valuable databases exist but, individually, none is enough to answer to all questions from health authorities, healthcare professionals, and patients. In order to obtain a complete overview on utilization, associated health outcomes and costs of these drugs, it seems necessary to better interlink available databases.

Targeting of under-75 years for the optimization of medication reconciliation with an approach based on medication risks: An observational study.

PURPOSE: To date, how medication reconciliation (MR) could be prioritized in younger patients remains poorly evaluated. This study aimed at assessing whether a MR prioritization strategy based on the identification of high-risk medication at patients' admission treatment could be of interest in non-elderly patients. METHOD: This prospective study was conducted between July and September 2017 in an internal medicine unit at Bordeaux teaching hospital. All patients aged 16 to 74 years and receiving at least two long-term treatments at admission were considered eligible. High-risk medications were defined on the basis of a pharmacovigilance study, which identified the drugs most involved in serious adverse effects reported in the Nouvelle-Aquitaine region in non-elderly adults. They included antithrombotics, analgesics, antipsychotics and cardiac therapies. MR-induced treatment changes were compared according to the existence of high-risk medications at admission in study participants. RESULTS: Among the 92 study participants, 46 presented with high-risk medications at admission (median age 66 years, IQR 58-70) and 46 without such (median age 54 years, IQR 47-64). High risk-medications (HRM) existing at admission were antithrombotics (52.2%) and antipsychotics (22.4%). MR resulted in treatment changes in 37% of patients admitted with at-risk medications vs. 8.7% of those admitted without such (P=0.001). Overall, the mean number of treatment changes performed after MR was of 1 (95%CI 0.4-1.6) in patients with high-risk medication at admission and of 0.2 (95%CI 0-0.4) in patients without such. MR-induced treatment changes assessed as clinically major at least once by pharmacists or clinicians was greater in HRM group (43.5%) than in non-HRM group (31.6%). However, the consistency was low between clinicians and pharmacists, especially to distinguish the clinical importance of significant and minor interventions. CONCLUSION: Targeting high-risk medications at admission appeared efficient for the prioritization of MR in non-elderly patients hospitalised in internal medicine.

Occurrences and Outcomes of Immune Checkpoint Inhibitors-Induced Vitiligo in Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: The use of immune checkpoint inhibitors (ICI) in melanoma and non-small cell lung cancer patients is associated with the onset of vitiligo. However, previous studies have suggested conflicting results on the conditions of occurrence of ICI-induced vitiligo. OBJECTIVE: The aim of this study was to describe the occurrences and outcomes of several cases of ICI-induced vitiligo. METHODS: A retrospective study was carried out using the French Pharmacovigilance Database (FPD) between the beginning of the commercialization of ICI in France and 1 January 2019, selecting for analysis the vitiligo reactions of patients due to treatment with ICI. RESULTS: Among the 95 case patients identified in the FPD, the median times to onset of vitiligo after the start of pembrolizumab, nivolumab and ipilimumab therapies were 5.4, 5.0, and 3.8 months, respectively. Furthermore, 37 patients (45%) discontinued ICI treatment due to disease progression. The median follow-up time of all patients was 33 months (interquartile range 2-56). CONCLUSIONS: This study provided an overall picture of ICI-induced vitiligo in daily medical practice on a large number of pharmacovigilance observations of case patients. Among the observations of ICI-induced vitiligo, the diagnosed cancer was melanoma for almost all patients. Most patients in the study experienced other associated adverse drug reactions (ADRs), such as colitis, pruritus, hypothyroidism, hyperthyroidism, thyroiditis, pancreatitis, and gastritis. Furthermore, our data suggest that the resolution of pembrolizumab- or nivolumab-induced vitiligo could be a marker of disease progression. Future studies evaluating vitiligo outcomes are warranted.

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.

Safety of levonorgestrel 52 mg intrauterine system compared to copper intrauterine device: a population-based cohort study.

OBJECTIVE: To compare the risk of all-cause death, hospitalizations (any cause), ectopic pregnancy, pelvic inflammatory disease or infection, uterine perforation, device removal, neuro-psychiatric drugs initiation, or new psychiatric visit(s) between levonorgestrel (LNG) 52 mg intrauterine system (IUS) and copper intrauterine device (IUD) users in France. STUDY DESIGN: We identified a historical cohort of women aged 20-55 years with a first dispensing of either LNG 52 mg IUS or copper-IUD between January 1, 2010, and December 31, 2014, in the French National Claims database, SNDS. We used propensity score matching to balance the two groups on baseline sociodemographic and clinical characteristics to minimize confounding. We estimated Cox proportional hazards models to compare health outcomes between LNG 52 mg IUS and copper-IUDs users. RESULTS: We matched 9318 LNG 52 mg IUS users (mean age 36.2±6.8 years) to 10,185 copper-IUD users (mean age 35.4±7.1 years). After matching and age-adjustment, LNG 52 mg IUS users had a slightly higher risk of anxiolytic drugs initiation (HR 1.08, 95%CI 1.01-1.15) and device removal (HR 1.05, 95%CI 1.01-1.10) compared to copper-IUD users, with no differences for other studied outcomes. CONCLUSION: French IUS users report slightly more anxiolytic treatment initiation and IUD removal compared to copper-IUD users. These results are consistent with a potential pharmacovigilance signal of anxiety-related disorders in LNG 52 mg IUS users. IMPLICATIONS STATEMENT: In French LNG 52 mg IUS users, there was slightly more anxiolytic treatment initiation and IUD removal compared to copper-IUD users. No risk difference was found for all-cause death, hospitalizations, ectopic pregnancy, pelvic disorders, and uterine perforation. We cannot exclude that the associations are related to differences in characteristics of women who chose each type of type of IUD.

Patterns of Use, Safety, and Effectiveness of Targeted Therapies in First-Line Treatment of Metastatic Colorectal Cancer According to Age: The STROMBOLI Cohort Study.

BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Their real-life evaluation is insufficient, especially in elderly and frail patients. The aim was to describe use, safety, and effectiveness of targeted therapies in first-line mCRC treatment according to age. PATIENTS AND METHODS: Two field cohorts of patients initiating bevacizumab or cetuximab for first-line mCRC were pooled. Patients characteristics, use, and safety were compared between younger and elderly patients (<75 vs. ≥75 years). Two-year overall survival (OS) and progression-free survival (PFS) were estimated in both age groups using the Kaplan-Meier method adjusted on factors associated with death or progression identified with Cox multivariate modeling. RESULTS: Eight hundred patients (n = 411, 51.4% bevacizumab) were included: 498 (62.3%) male, median age 64 years, 118 (14.8%) Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. Elderly patients (n = 126, 15.8%) were more often treated with 5-fluorouracil alone than younger. Severe adverse events were equivalent across age groups. ECOG-PS ≥1, abnormal hemoglobin, and abnormal alkaline phosphatases were associated with a higher risk of death; OS adjusted on these factors was similar between elderly and younger patients. ECOG-PS ≥1, lung metastases, abnormal hemoglobin, and abnormal creatinine clearance were associated with a higher risk of progression or death; PFS adjusted on these factors was similar across groups. CONCLUSION: Despite treatment adaptations, elderly patients could benefit from targeted therapies as younger without safety warning.