GLP-1 RAs are peptides used to treat patients with T2D. Anaphylaxis has been observed with these treatments, and in the lixisenatide development program, more cases of anaphylaxis were reported for ...lixisenatide than placebo (0.2% vs 0.1%). The aim was to assess anaphylaxis incidence rates (IRs) among patients with T2D initiating GLP-1 RAs, with a focus on lixisenatide. We conducted a cohort study in 3 large US claims databases using data from 2017-2021. We included new users of GLP-1 RAs with T2D aged ≥18 years and enrolled ≥6 months in the database before GLP-1 RA initiation (start of follow-up). Medications included were: lixisenatide and insulin glargine/lixisenatide, exenatide, liraglutide and insulin degludec/liraglutide, dulaglutide, and semaglutide. We identified the first anaphylaxis event during follow-up using a validated algorithm. We report anaphylaxis crude IRs and 95% confidence intervals (CIs) for each medication cohort, pooled across data sources. There were 696,089 new users with 456,612 person-years (p-y) of exposure to GLP-1 RAs. Baseline characteristics (demographics, medications, medical conditions) were similar across the medication cohorts. IRs ranged from 1.0 (lixisenatide) to 6.0 (exenatide) per 10,000 p-y with wide 95% confidence intervals (Figure). Anaphylaxis is rare with GLP-1 RA treatments. Lixisenatide is unlikely to confer higher risk of anaphylaxis than other GLP-1 RAs.
Disclosure
M.S.Anthony: Other Relationship; Sanofi. C.W.Saltus: Other Relationship; Sanofi. S.Berreghis: Employee; Sanofi. L.E.Parlett: Employee; HealthCore Inc., Research Support; Sanofi. C.Bocage: Employee; Anthem, Inc, Stock/Shareholder; Anthem, Inc. K.E.Walsh: Consultant; Sanofi. J.Juhaeri: Employee; Sanofi. C.Johannes: Other Relationship; Sanofi-Aventis U.S. L.Djebarri: Employee; Sanofi. D.C.Beachler: Employee; Anthem, Inc, HealthCore Inc. V.R.Aroda: Consultant; Applied Therapeutics Inc., Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Applied Therapeutics Inc., Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Sanofi. B.Calingaert: Other Relationship; Sanofi. C.Pan: None. C.Crowe: Employee; HealthCore Inc. S.Lanes: None. K.J.Rothman: None.
Identifying health outcomes in healthcare databases Lanes, Stephan; Brown, Jeffrey S.; Haynes, Kevin ...
Pharmacoepidemiology and drug safety,
October 2015, 2015-Oct, 20151001, Letnik:
24, Številka:
10
Journal Article
We conducted a study to assess whether testosterone therapy (TT) alters prostate cancer risk using a large U.S. commercial insurance research database.
From the HealthCore Integrated Research ...Database (HIRD), we selected men ages 30 years or greater who were new users of TT during 2007 to 2015. We selected two comparison groups: (i) unexposed (matched 10:1) and (ii) new users of phosphodiesterase type 5 inhibitor (PDE5i). Incident prostate cancer was defined as diagnosis of prostate cancer within 4 weeks following prostate biopsy. Propensity scores and inverse probability of treatment weights were used in Poisson regression models to estimate adjusted incidence rates, incidence rate ratios (IRR), and 95% confidence intervals (CI). Subgroup analyses included stratification by prostate cancer screening, hypogonadism, and follow-up time.
The adjusted prostate cancer IRR was 0.77 (95% CI, 0.68-0.86) when comparing TT with the unexposed group and 0.85 (95% CI, 0.79-0.91) in comparison with the PDE5i group. Inverse associations between TT and prostate cancer were observed in a majority of subgroup analyses, although in both comparisons estimates generally attenuated with increasing time following initial exposure. Among TT users, duration of exposure was not associated with prostate cancer.
Men who received TT did not have a higher rate of prostate cancer compared with the unexposed or PDE5i comparison groups. The inverse association between TT and prostate cancer could be the result of residual confounding, contraindication bias, or undefined biological effect.
This study suggests that limited TT exposure does not increase risk of prostate cancer in the short term.
To measure prevalence, incidence, and mortality of cardiovascular outcomes among persons with chronic obstructive pulmonary disease (COPD) and to assess the extent these outcomes differ from persons ...without COPD.
Retrospective cohort study in longitudinal health care databases maintained by the government of Saskatchewan, Canada. Subjects were persons age 40 years or older who were diagnosed with COPD during 1997-2000 and who received two or more prescriptions for bronchodilators within 6 months of diagnosis. Each subject was matched by age and sex to two controls without COPD or asthma.
Of COPD patients (n = 11,493), 54% were male, and 74% were 65 years or older. Prevalence of all cardiovascular diseases was higher in the COPD group than in the comparison group. After adjusting for cardiovascular risk, odds ratios of prevalence were: arrhythmia 1.76 (confidence interval CI: 1.64-1.89), angina 1.61 (CI: 1.47-1.76), acute myocardial infarction 1.61 (CI: 1.43-1.81), congestive heart failure 3.84(CI: 3.56-4.14), stroke 1.11 (CI: 1.02-1.21), pulmonary embolism 5.46 (CI: 4.25-7.02). Risk of hospitalization due to each cardiovascular cause was elevated in the COPD group. The risk ratio for cardiovascular mortality was 2.07 (CI: 1.82-2.36) and all cause mortality was 2.82 (CI: 2.61-3.05).
Persons with diagnosed and treated COPD are at increased risk for hospitalizations and deaths due to cardiovascular diseases.
Purpose
Real‐world evidence (RWE) is increasingly used for medical regulatory decisions, yet concerns persist regarding its reproducibility and hence validity. This study addresses reproducibility ...challenges associated with diversity across real‐world data sources (RWDS) repurposed for secondary use in pharmacoepidemiologic studies. Our aims were to identify, describe and characterize practices, recommendations and tools for collecting and reporting diversity across RWDSs, and explore how leveraging diversity could improve the quality of evidence.
Methods
In a preliminary phase, keywords for a literature search and selection tool were designed using a set of documents considered to be key by the coauthors. Next, a systematic search was conducted up to December 2021. The resulting documents were screened based on titles and s, then based on full texts using the selection tool. Selected documents were reviewed to extract information on topics related to collecting and reporting RWDS diversity. A content analysis of the topics identified explicit and latent themes.
Results
Across the 91 selected documents, 12 topics were identified: 9 dimensions used to describe RWDS (organization accessing the data source, data originator, prompt, inclusion of population, content, data dictionary, time span, healthcare system and culture, and data quality), tools to summarize such dimensions, challenges, and opportunities arising from diversity. Thirty‐six themes were identified within the dimensions. Opportunities arising from data diversity included multiple imputation and standardization.
Conclusions
The dimensions identified across a large number of publications lay the foundation for formal guidance on reporting diversity of data sources to facilitate interpretation and enhance replicability and validity of RWE.
Idiopathic pulmonary fibrosis is a life-threatening condition, and few data concerning the impact on healthcare utilization and associated costs are available. The objective of this study was to ...describe the burden of illness (comorbidity, healthcare resource utilization, and associated costs) in patients with idiopathic pulmonary fibrosis.
Two cohorts (patients with idiopathic pulmonary fibrosis and matched controls) were retrospectively identified from US claims databases between January 1, 2001 and September 30, 2008. Cases with idiopathic pulmonary fibrosis were defined by age of 55 years or older and either two or more claims with a code for idiopathic fibrosing alveolitis (ICD-9 516.3), or one claim with ICD 516.3 and a subsequent claim with a code for post-inflammatory pulmonary fibrosis (ICD-9 515). The prevalence and incidence of pre-selected comorbidities, healthcare resource utilization (hospital, outpatient, drugs), and direct medical costs were assessed in each cohort.
A total of 9286 patients with idiopathic pulmonary fibrosis were identified. When compared with age- and gender-matched controls, these patients were at significantly increased risk for comorbidities including pulmonary hypertension and emphysema. The all-cause hospital admission rate (0.5 per person-year) and the all-cause outpatient visit rate (28.0 per person-year) were both ∼2-fold higher than in controls. Total direct costs for patients with idiopathic pulmonary fibrosis were $26,378 per person-year; the incremental costs over controls were $12,124 (2008 value).
Patients with idiopathic pulmonary fibrosis experience increased comorbidity, healthcare resource utilization, and direct medical costs compared to controls.
Prostate cancer is a commonly studied outcome in administrative claims studies, but there is a dearth of validated case identifying algorithms. The long-term development of the disease increases the ...difficulty in separating prevalent from incident prostate cancer. The purpose of this validation study was to assess the accuracy of a claims algorithm to identify incident prostate cancer among men in commercial and Medicare Advantage US health plans.
We identified prostate cancer in claims as a prostate cancer diagnosis within 28 days after a prostate biopsy and compared case ascertainment in the claims with the gold standard results from the Georgia Comprehensive Cancer Registry (GCCR).
We identified 74,008 men from a large health plan claims database for possible linkage with GCCR. Among the 382 prostate cancer cases identified in claims, 312 were also identified in the GCCR (positive predictive value PPV = 82%). Of the registry cases, 91% (95% confidence interval = 88, 94) were correctly identified in claims. Claims and registry diagnosis dates of prostate cancer matched exactly in 254/312 (81%) cases. Nearly half of the false-positive cases also had claims for prostate cancer treatment. Thirteen (43%) false-negative cases were classified as noncases by virtue of having a biopsy and diagnosis >28 days apart as required by the algorithm. Compared to matches, false-negative cases were older men with less aggressive prostate cancer.
Our algorithm demonstrated a PPV of 82% with 92% sensitivity in ascertaining incident PC. Administrative health plan claims can be a valuable and accurate source to identify incident prostate cancer cases.
This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks ...varied by number and severity of exacerbation in a commercially insured population in the United States.
This was a retrospective cohort study of newly diagnosed COPD patients ≥40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the "exacerbation cohort". Moderate exacerbations were outpatient visits with contemporaneous antibiotic or glucocorticoid administration; severe exacerbations were emergency department visits or hospitalizations for AECOPD. Follow-up started on the exacerbation date. Distribution of time between diagnosis and first exacerbation was used to assign index dates to the "unexposed" cohort. Cox proportional hazards models estimated risks of a cardiovascular event or death following an exacerbation adjusted for medical and prescription history and stratified by follow-up time, type of cardiovascular event, exacerbation severity, and rank of exacerbation (first, second, or third).
Among 435,925 patients, 170,236 experienced ≥1 exacerbation. Risk of death was increased for 2 years following an exacerbation and was highest during the first 30 days (any exacerbation hazard ratio (HR)=1.79, 95% CI=1.58-2.04; moderate HR=1.22, 95% CI=1.04-1.43; severe HR=5.09, 95% CI=4.30-6.03). Risks of cardiovascular events were increased for 1 year following an AECOPD and highest in the first 30-days (any exacerbation HR=1.34, 95% CI=1.23-1.46; moderate HR=1.23 (95% CI 1.12-1.35); severe HR=1.93 (95% CI=1.67-2.22)). Each subsequent AECOPD was associated with incrementally higher rates of both death and cardiovascular events.
Risk of death and cardiovascular events was greatest in the first 30 days and rose with subsequent exacerbations. Risks were elevated for 1-2 years following moderate and severe exacerbations, highlighting a sustained increased cardiopulmonary risk associated with exacerbations.
To assess the effect on FEV1 and clinical outcomes of adding ipratropium bromide to salbutamol in the treatment of acute asthma.
We conducted a pooled analysis of three randomized double-blinded ...clinical trials conducted in the United States, Canada, and New Zealand. The studies enrolled 1,064 patients aged 18 to 55 years who presented at the emergency department with acute asthma. Patients were randomized to treatment with a combination of nebulized 2.5 mg salbutamol plus 0.5 mg ipratropium bromide, or 2.5 mg salbutamol alone. Medications were administered at baseline and, in the US study, at 45 min. FEV1 was measured at baseline, 45 min, and 90 min. Patients were followed up for 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization.
Treatment groups were comparable at baseline. Of the 1,064 patients randomized, 1,015 patients (95%) remained in the study for measurement at 45 min, and 961 patients (90%) completed the final measurement at 90 min. Comparison of overall improvement in FEV1 at 45 min indicated a better response for patients receiving combination therapy (mean difference=43 mL, 95% confidence interval CI=-20, 107). The distribution of change in FEV1 was skewed by a small number of patients with extreme values (38 of 1,064=3.6%) that may have been due to unreliable lung function testing. Removing these outliers produced a larger and more precise estimate of effect (mean difference=55 mL, 95% CI=2,107). Because the distribution was skewed, we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy. The difference between median values at 45 min is 40 mL (Wilcoxon p value=0.03). In addition, 4.9% (95% CI=-1%, 11%) more patients in the combination group achieved at least 20% of their potential improvement, as measured by the difference between their baseline FEV1 and their predicted FEV1. Patients receiving combination therapy had lower risk for each of three clinical outcomes: the need for additional treatment (relative risk RR=0.92, 95% CI=0.84, 1.0), risk of asthma exacerbation (RR=0.84, 95% CI=0.67, 1.04), and risk of hospitalization (RR=0.80, 95% CI=0.61, 1.06).
Adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function, and reduces the risk of the need for additional treatment, subsequent asthma exacerbations, and hospitalizations. These apparent benefits of adding ipratropium bromide were independent of the amount of beta-agonist that had been used earlier in the attack, and possibly related to a recent upper respiratory tract infection. Confirmatory studies are needed, especially for clinical outcomes.
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