Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID-19 Pandemic

Objective: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control. Results: More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. Conclusion: Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.</p

Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries

INTRODUCTION: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. METHODS AND ANALYSIS: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. ETHICS AND DISSEMINATION: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences

Safety of levonorgestrel 52mg 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) 52mg intrauterine system (IUS) and copper intrauterine device (IUD) users in France. STUDY DESIGN: We identified a historical cohort of women aged 20-55years with a first dispensing of either LNG 52mg 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 52mg IUS and copper-IUDs users. RESULTS: We matched 9318 LNG 52mg IUS users (mean age 36.2+/-6.8years) to 10,185 copper-IUD users (mean age 35.4+/-7.1years). After matching and age-adjustment, LNG 52mg IUS users had a slightly higher risk of anxiolytic drugs initiation (HR 1.08, 95%CI 1.01 to 1.15) and device removal (HR 1.05, 95%CI 1.01 to 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 52mg IUS users. IMPLICATIONS STATEMENT: In French LNG 52mg 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

Does Ibuprofen worsen COVID-19 Disease?

Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche

NSAIDs and COVID-19: A Systematic Review and Meta-analysis

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been discouraged for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, fearing that they could increase the risk of infection or the severity of SARS-CoV-2. METHODS: Original studies providing information on exposure to NSAIDs and coronavirus disease 2019 (COVID-19) outcomes were retrieved and were included in a descriptive analysis and a meta-analysis with Cochrane Revue Manager (REVMAN 5.4), using inverse variance odds ratio (OR) with random- or fixed-effects models. RESULTS: Of 92,853 papers mentioning COVID-19, 266 mentioned NSAIDs and 61 mentioned ibuprofen; 19 papers had analysable data. Three papers described NSAID exposure and the risk of SARS-CoV-2 positivity, five papers described the risk of hospital admission in positive patients, 10 papers described death, and six papers described severe composite outcomes. Five papers studied exposure to ibuprofen and death. Using random-effects models, there was no excess risk of SARS-CoV-2 positivity (OR 0.86, 95% confidence interval [CI] 0.71-1.05). In SARS-CoV-2-positive patients, exposure to NSAIDs was not associated with excess risk of hospital admission (OR 0.90, 95% CI 0.80-1.17), death (OR 0.88, 95% CI 0.80-0.98), or severe outcomes (OR 1.14, 95% CI 0.90-1.44). With ibuprofen, there was no increased risk of death (OR 0.94, 95% CI 0.78-1.13). Using a fixed-effect model did not modify the results, nor did the sensitivity analyses. CONCLUSION: The theoretical risks of NSAIDs or ibuprofen in SARS-CoV-2 infection are not confirmed by observational data

Eur J Clin Pharmacol

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

Ambulatory drug changes in the elderly after hospital discharge: A cohort study

AIM: To describe the ambulatory changes in drug prescriptions 3 months after hospital discharge among elderly patients aged 75 and over, and to identify the reasons for these changes. METHODS: A prospective cohort study was conducted on subjects, discharged between 09/2016 and 01/2017 from the Bordeaux University Hospital. Prescription forms were collected from patients' pharmacists. The main outcome was the occurrence of at least one significant change (SC) defined as an initiation, a discontinuation, a switch or change in drug daily dosage as regards the drugs prescribed upon hospital discharge and those prescribed 3 months after. Whenever drug SC occurred, general practitioners were requested to elicit reasons for such changes. RESULTS: Among the 126 patients included in our study, 73 underwent a 3-month follow-up period, without death or being re-hospitalised. 87.7% of them had at least one SC 3 months after discharge, with an average of 3.1±2.5 SC per patient. Main changes involved: discontinuation or dose decrease of anxiolytics, hypnotics, antalgics, betablockers and calcium channel blockers; start or dose increase of diuretics, ACE inhibitors and angiotensin receptor blockers. In patients with a 3-month follow-up period, 27.4% underwent at least one ADR-induced SC. CONCLUSION: Most elderly patients experience drug prescription changes after discharge. Some, according to drug iatrogenic, could be avoided through better cooperation between hospital and ambulatory prescribers

Therapie

Some concerns have emerged about the evidence of benefits on survival outcomes or quality of life of new anticancer drugs. In parallel, the decreased cancer mortality leads to an increased number of patients exposed to cancer treatment-related consequences. In this context, pharmacoepidemiology is crucial to assess anticancer drug use, effectiveness and safety in real life conditions. We aimed to describe strengths, limitations and considerations associated with the use of the French national health insurance database (systeme national des donnees de sante [SNDS]) to conduct pharmacoepidemiological studies in oncology. The SNDS represents a powerful tool in pharmacoepidemiology owing to its extensive coverage, accurate description and quantification of drug exposure and individual data on patients. The main limitations of this database ensue from the administrative nature resulting in technical difficulties in its management and gaps in availability of data. Another limitation is the lack of accurate identification of diseases, comorbidities or outcomes and potential confounding with notably the lack of data regarding cancer stage, prognosis or risk factors. Finally, the accurate identification of the nature of chemotherapy received by patients is sometimes complex. To minimize these limitations, several approaches and statistical methods could be used as highlighted by national or international initiatives. First, the SNDS may be linked with cancer registry or clinical data. Then, several data sources could be combined using meta-analytical methods. The development of methodological tools and the use of standardized methods are crucial to enhance the quality of studies that can impact clinical practice and guide public decision. Pharmacoepidemiological approaches and pharmacovigilance represent an important cornerstone in oncology for signal detection or long-term follow up of cancer patients. In this context, validated methods to identify cancer patients and to describe chemotherapy regimens within these data should be promoted and remain too scarce despite international guidelines. Moreover, limits and strength of each data sources should be systematically discussed according to the research question. Optimized and framed use of claims database represents a future challenge in onco-pharmacoepidemiology

Br J Clin Pharmacol

Aims : To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting. Methods : A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1–3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively. Results : Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61–0.86]) and TERI (0.81 [0.68–0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts. Conclusion : DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM)