US Healthcare Claims Database Research Articles

Maternal and Infant Morbidity and Mortality in relation to Delivery Mode in a large US Healthcare Claims Database in 2019 and 2020.

Provide contemporary data on maternal and infant outcomes after delivery to better understand risks of Cesarean section (CS). Data for deliveries in 2019 and 2020 were obtained from a large US commercial healthcare claims database. Maternal morbidity measures included twenty Severe Maternal Morbidity (SMM) outcomes and seven additional obstetric and mental health outcomes. Infant morbidity measures included eight outcomes related to respiratory health, digestive health, atopic dermatitis, and birth trauma. Outcome prevalence was ascertained at 42 days (maternal only) and 360 days after delivery. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for prevalence adjusted for risk factors for delivery mode and each outcome. Analyses were conducted for 2019 and 2020 to assess the influence of the COVID-19 pandemic. A total of 436,991 deliveries were identified (145,061 CS; 291,930 vaginal). The prevalence of SMM was 3.3% at 42 days and 4.1% at 360 days. The covariate-adjusted odds of SMM were higher among CS than vaginal deliveries at 42 days (OR: 2.0, 95% CI: 1.9, 2.1) and 360 days (OR: 1.7, 95% CI: 1.7, 1.8). There were 226,983 infants available for analysis of outcomes at 360 days. Most adverse infant outcomes were more prevalent at 360 days among CS than vaginal deliveries, and the covariate-adjusted odds of any adverse infant outcome at 360 days were higher among CS than vaginal deliveries (OR: 1.2; 95% CI: 1.1, 1.3). Respiratory morbidity was most affected by delivery mode. Maternal and infant mortality up to 360 days was rare. Similar trends were observed in the 2019 and 2020 cohorts. This observational study, performed using recent data obtained from a large US commercial claims database, provides contemporary evidence of risks to mothers and infants of CS relative to vaginal delivery.

Emulating Randomized Trials by Observational Database Studies: The RCT-DUPLICATE Initiative in COPD and Asthma.

Observational studies are increasingly used to provide real-world evidence in regulatory decision-making. The RCT-DUPLICATE initiative conducted observational studies emulating two trials in patients with asthma and three in COPD. For each trial, new-user cohorts were constructed from two US healthcare claims databases, comparing initiators of the study and comparator drugs, matched on propensity scores. Proportional hazards models were used to compare the treatments on study outcomes. The observational studies involved more subjects than the corresponding trials, with treatment arms well-matched on baseline characteristics. An asthma example involved emulation of the 26-week FDA-mandated D5896 trial. With 6,494 asthma patients per arm, the hazard ratio (HR) of a serious asthma-related event with budesonide-formoterol versus budesonide was 1.29 (95% CI: 0.63-2.65), compared with 1.07 (95% CI: 0.70-1.65) in the trial. A COPD example is the emulation of the one-year IMPACT trial. With 4,365 COPD patients per arm, the HR of a COPD exacerbation with triple therapy versus dual bronchodilators was 1.08 (95% CI: 1.00-1.17), compared with 0.84 (95% CI: 0.78-0.91) in the trial. We found mainly discordant results between observational analyses and randomized trials, likely from the forced discontinuation of treatments prior to randomization in the trials, not mimicable in the observational analyses.

COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in PBC patients improve with OCA therapy. Patients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score-weighted EC group was derived from a US healthcare claims database. In the RCT, the primary endpoint occurred in 28.6% of OCA (n=168) and 28.9% of placebo patients (n=166; intent-to-treat [ITT] analysis hazard ratio [HR]=1.01, 95% CI=0.68-1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting (IPCW) and as-treated analyses shifted the HR to favor OCA. In the EC (n=1051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR=0.39; 95% CI=0.22-0.69; P=0.001). No new safety signals were identified in the RCT. Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the ITT estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC.

Abstract PO2-12-07: Risk of anaphylaxis associated with the use of pertuzumab or other biologics with potential for use outside the hospital

Abstract BACKGROUND Intravenous (IV) pertuzumab (P) and trastuzumab (H) are approved in the US for the treatment of HER2-positive breast cancer. P and H are also approved as a fixed-dose combination for SC injection (pertuzumab, trastuzumab, and hyaluronidase-zzxf; PH FDC SC). PH FDC SC may offer the possibility of treatment outside a hospital setting by a healthcare professional. Anaphylactic reactions can be a concern with the use of biologics. PH is also frequently initiated with six to eight cycles of taxanes, which can also be associated with anaphylaxis. We used administrative claims data to evaluate the risk of anaphylaxis associated with the real-world administration of PH or other biologic drugs in the real world. Our objective was to evaluate the risk of anaphylaxis associated with the administration of P and to contextualize the risk estimate by using other biologics that can be used outside the hospital as a benchmark. METHODS Cohorts of incident users were selected using retrospective records from a US healthcare claims database (IQVIA). Patients included were privately insured in the US, aged 16 to 65 years, and initiated a treatment of interest between 2012 and 2021. Possible and severe anaphylactic events (PAEs) were identified using the algorithm developed by the US Food and Drug Administration (FDA) Sentinel Initiative and updated with ICD10 codes (PMID: 34181291). PAEs were attributed to a drug if it occurred on the day of administration or the day after. The prevalence proportion (PP) of PAE was used to approximate the risk of anaphylaxis at each cycle. A sensitivity analysis using the proportion of prior P use amongst the cases of PAE beyond cycle 1 in the H cohort was conducted to approximate how many cases of PAE could have been missed at cycle 1 of P due to a depletion of susceptibles (as P IV and H may be administered sequentially in any order, patients with a PAE from H would not receive scheduled P and thus be excluded from the P cohort). RESULTS A total of 1,919,748 patients constituted 27 cohorts. Of them, 184,414 patients initiated monoclonal antibodies (mAbs) in 12 cohorts of which 12,264 and 184 initiated P IV and PH FDC SC, respectively. In the P IV cohort, seven PAE events were observed up to cycle 6 and none after. The PP at cycle 1 of P was 1.63 per 10,000 patients (95% confidence interval [CI] = 0.45, 5.94). The risk was comparable to that of other mAbs where anaphylaxis risk is described as uncommon/rare (Table). Accounting for a potential depletion of susceptibles increased the PP at cycle 1 of P to 2.45/10,000 (95% CI = 0.83, 7.19). No PAEs were reported in patients treated with PH FDC SC. CONCLUSIONS Using one of the largest datasets available, results suggest the risk of PAE with P administration could be within the range of what is observed with other mAbs that can be administered outside of the hospital. All events were observed when patients are expected to receive treatment at the hospital due to taxane administration. No PAE events were identified for PH FDC SC, but there were few patients in this cohort. Efforts are ongoing to identify a larger cohort treated with PH FDC SC. Risk of anaphylaxis by mAb * According to summary of product characteristics. † ≥1/1,000 to <1/100. ‡ ≥1/10,000 to <1/1,000. CI = confidence interval; H = trastuzumab; IV = intravenous; P = pertuzumab; PH FDC SC = pertuzumab, trastuzumab, and hyaluronidase-zzxf. Citation Format: Thibaut Sanglier, Tom Chambers, Joanna Harton, Laurentia Wahyudi, Magali Genevray, Eleonora Restuccia, Cécile Droz-Perroteau, Chau Dang. Risk of anaphylaxis associated with the use of pertuzumab or other biologics with potential for use outside the hospital [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-07.

Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study.

To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

Diagnosed and Drug-Treated Prevalence of Essential Tremor in Pediatric Patients: Retrospective Analyses of Two US Healthcare Claims Databases (S51.003)

Diagnosed and Drug-Treated Prevalence of Essential Tremor in Pediatric Patients: Retrospective Analyses of Two US Healthcare Claims Databases (S51.003)

Diagnosed and Drug-Treated Prevalence of Essential Tremor in Adult Patients: Retrospective Analyses of Two US Healthcare Claims Databases (S51.004)

Diagnosed and Drug-Treated Prevalence of Essential Tremor in Adult Patients: Retrospective Analyses of Two US Healthcare Claims Databases (S51.004)

Impact of Vagus Nerve Stimulation for the Treatment of Drug-resistant Epilepsy on Patterns of Use and Cost of Health Care Services and Pharmacotherapy: Comparisons of the 24-Month Periods Before and After Implantation

PurposeThis study examines the impact of vagus nerve stimulation (VNS) as treatment for drug-resistant epilepsy (DRE) on the use and cost of health care services and pharmacotherapy. MethodsUsing a large US health care claims database, we identified all patients with DRE who underwent VNS between January 1, 2012 and December 31, 2019. VNS implantation date was designated as the index date, and patients had to be continuously enrolled for the 24-month period before this date (preindex period). Outcomes included all-cause and epilepsy-related hospitalization, emergency department (ED) visits, and health care costs; health care claims resulting in an epilepsy diagnosis and all claims for antiseizure medications were deemed epilepsy related. Preindex data, except care related to preoperative medical clearance for VNS, were used to estimate multivariate regression models predicting outcomes during the 24-month postindex period (follow-up period). Predicted outcomes during follow-up were then compared with observed values. As a sensitivity analysis, we also replicated all analyses among subgroups defined by comorbid depression. FindingsA total of 659 patients underwent VNS for DRE and met the selection criteria. For the composite outcome of all-cause hospitalizations and ED visits, observed values were 42% lower than expected during the 24-month follow-up period; for the composite outcome of epilepsy-related hospitalizations and ED visits, observed values were 49% lower (P < 0.001 for both). Observed mean total all-cause costs, inclusive of costs of the procedure, were not significantly different than expected costs by month 19 of follow-up; mean total epilepsy-related costs were comparable by month 18. Findings were similar in subgroups with and without depression, although nominally greater differences (observed – expected) were seen in those with comorbid depression. ImplicationsOur findings suggest that VNS is associated with decreased risk of hospitalization or ED visits (all cause and epilepsy related) during the 2-year period subsequent to implantation and may become cost-neutral within 2 years of implantation (vs continued medical management of DRE without VNS). Although expected outcomes were estimated based on the 24-month period before implantation, the degree to which they approximated what would have happened in the absence of VNS is unknowable. Further research is needed to better understand the extend and duration of the impact of VNS on seizure frequency and severity and health-related quality of life, including its performance among those with and without comorbid depression.

Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database

Aim Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. Materials and methods We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. Results Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. Limitations Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. Conclusions After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

EE209 Real-World Opioid Overdose Patient Trends, Costs, and Comorbidities in the United States (2016-2019)

CDC indicates over 70% of drug overdoses involved a prescription or illicit opioid. A US healthcare claims database was analyzed to assess trends, baseline comorbidities, and per member per month costs (PMPMC) among opioid overdose patients (OOP).

EE9 Real-World Naloxone Prescription Trends, Costs, and Comorbidities in Commercial, Managed Medicare, and Medicaid Patients in the United States (2016-2019)

CDC recommends naloxone co-prescribing for at-risk prescription opioid patients. A large US healthcare claims database was analyzed to assess the prescription naloxone patient trends and other characteristics.

Development of a Novel Algorithm to Identify People with High Likelihood of Adult Growth Hormone Deficiency in a US Healthcare Claims Database.

Objective Adult growth hormone deficiency (AGHD) is an underdiagnosed disease associated with increased morbidity and mortality. Identifying people who may benefit from growth hormone (GH) therapy can be challenging, as many AGHD symptoms resemble those of aging. We developed an algorithm to potentially help providers stratify people by their likelihood of having AGHD. Design The algorithm was developed with, and applied to, data in the anonymized Truven Health MarketScan® claims database. Patients. A total of 135 million adults in the US aged ≥18 years with ≥6 months of data in the Truven database. Measurements. Proportion of people with high, moderate, or low likelihood of having AGHD, and differences in demographic and clinical characteristics among these groups. Results Overall, 0.5%, 6.0%, and 93.6% of people were categorized into groups with high, moderate, or low likelihood of having AGHD, respectively. The proportions of females were 59.3%, 71.6%, and 50.4%, respectively. People in the high- and moderate-likelihood groups tended to be older than those in the low-likelihood group, with 58.3%, 49.0%, and 37.6% aged >50 years, respectively. Only 2.2% of people in the high-likelihood group received GH therapy as adults. The high-likelihood group had a higher incidence of comorbidities than the low-likelihood group, notably malignant neoplastic disease (standardized difference −0.42), malignant breast tumor (−0.27), hyperlipidemia (−0.26), hypertensive disorder (−0.25), osteoarthritis (−0.23), and heart disease (−0.22). Conclusions This algorithm may represent a cost-effective approach to improve AGHD detection rates by identifying appropriate patients for further diagnostic testing and potential GH replacement treatment.

Indicators of Suboptimal Treatment and Associated Healthcare Costs Among Patients With Crohn's Disease Initiated on Biologic or Conventional Agents.

As the treatment landscape for Crohn's disease (CD) evolves, an up-to-date understanding of the burden associated with indicators of suboptimal treatment is needed. The aim of this study was to describe suboptimal treatment indicators and associated healthcare costs among CD patients initiated on a biologic or conventional agent. Adults with CD were identified in a US healthcare claims database (Optum's Clinformatics Data Mart; 01/2004-03/2019). The first biologic or conventional agent claim within 12 months of a CD diagnosis was the index date/agent. Indicators of suboptimal treatment (nonadherence, dose escalation, chronic corticosteroid use, augmentation, ≥1 CD surgery, ≥2 CD emergency department visits, ≥1 CD inpatient (IP) stay, switch, cycling, restart, inadequate induction) were identified in the 12-month postindex landmark period. The mean per-patient-per-year (PPPY) healthcare costs (2019 USD) were evaluated in the year postlandmark. There were 5107 patients (mean age ~44 years, 56% female) in the biologic and 6072 patients (~51 years; 59% female) in the conventional cohort. In the biologic cohort, 79.4% of patients had ≥1 suboptimal treatment indicator. Mean PPPY healthcare costs increased with the number of suboptimal treatment indicators, from $46 100 (no indicator) to $68 572 (≥4 indicators). The conventional cohort had similar patterns: 72.5% of patients presented ≥1 suboptimal treatment indicator, and mean PPPY healthcare costs increased from $17 329 (no indicator) to $67 568 (≥4 indicators). In both cohorts, IP and outpatient medical costs (excluding biologics) contributed a major portion of the increase. Among CD patients, suboptimal treatment indicators were common and were associated with an increased burden to the healthcare system.

1145-P: Individual SGLT2 Inhibitors and the Risk of Diabetic Ketoacidosis

SGLT2 inhibitors (SGLT2i) are increasingly prescribed to treat type 2 diabetes (T2D) given their cardiovascular benefits. However, SGLT2i are known to increase the risk of diabetic ketoacidosis (DKA) , a rare yet serious outcome. It remains unclear whether individual SGLT2i are associated with a differential risk of DKA. Using 3 US healthcare claims databases (1/2014 - 12/2020) we assembled 2 cohorts of adults with T2D initiating (1) individual SGLT2i, i.e., canagliflozin, dapagliflozin, or empagliflozin, for a within-class comparison between SGLT2i (cohort #1, median age=62 years, 55% male) , and (2) individual SGLT2i or dulaglutide, for comparisons between SGLT2i and an out-of-class comparison (cohort #2, median age=63 years, 54% male) . Cohorts were reweighed using inverse probability of treatment weights, accounting for &amp;gt;130 baseline patient characteristics. Hazard ratios (HRs) and 95% CIs were estimated for hospitalization for DKA in each database and pooled using random-effects models. Over a median follow-up of 6 months, neither empagliflozin [HR (95% CI) = 0.96 (0.78-1.19) ], or dapagliflozin [HR (95% CI) = 0.76 (0.58-1.01) ] had a differential DKA risk vs. canagliflozin. All 3 SGLT2i were associated with a similar increase in DKA risk vs. dulaglutide (Table) . In this large cohort study, we found no difference in the risk of DKA across individual SGLT2i, but all SGLT2i types were associated with an increased risk of DKA vs. dulaglutide. Disclosure D.Abrahami: None. E.D'andrea: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. J.M.Paik: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20326)

1146-P: SGLT2 Inhibitors and the Risk of Early Bladder Cancer Events

SGLT2 inhibitors (SGLT2is) have been shown to reduce the risk of cardiovascular and mortality events in large cardiovascular outcome trials in patients with type 2 diabetes. However, their safety profile is controversial, with some trials reporting imbalances in bladder cancer events, all of which occurred relatively soon after randomization. To address this safety concern, we used 3 US healthcare claims databases and 1 UK primary care database (01/2013-12/2020) . In each database, we identified adults newly treated with either SGLT2is (total n=453,726) or GLP-1 receptor agonists (GLP1RAs, n=375,990) (comparison #1) , and SGLT2is (n=347,055) or DPP-4 inhibitors (DPP4is, n=854,141) (comparison #2) . Propensity score-based fine stratification was used to reweigh the cohorts, adjusting for a wide range of patient characteristics at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for bladder cancer in each database using Cox proportional hazards models. After a median follow-up of 1.8 years, use of SGLT2is may slightly reduce the risk of bladder cancer, compared to GLP1RAs [HR (95% CI) =0.90 (0.81-1.00) ]. Compared to use of DPP4is, SGLT2is are not associated with bladder cancer incidence [HR (95% CI) : 1.00 (0.91-1.11) ] after a median follow-up of 2.0 years (Table) . Overall, the results of this large international cohort study provide reassurance on the short-term effects of SGLT2is on bladder cancer incidence. Disclosure D.Abrahami: None. H.Tesfaye: None. H.Yin: None. O.Yu: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck &amp; Co., Inc., Nant Pharma, Pfizer Inc. S.Schneeweiss: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. L.Azoulay: Consultant; Pfizer Inc. Funding Canadian Institutes of Health Research (PJT-169040)

Clinical characteristics and disease outcomes in non-diabetic chronic kidney disease: retrospective analysis of a US healthcare claims database

BackgroundThe observational, real-world evidence FLIEDER study aimed to describe patient clinical characteristics and investigate clinical outcomes in non-diabetic patients with chronic kidney disease (CKD) using data collected from routine clinical practice in the United States.MethodsBetween 1 January, 2008–31 December, 2018, individuals aged ≥ 18 years, with non-diabetic, stage 3–4 CKD were indexed in the Optum® Clinformatics® Data Mart US healthcare claims database using International Classification of Diseases-9/10 codes for CKD or by laboratory values (estimated glomerular filtration rate [eGFR] 15–59 mL/min/1.73 m2). The primary outcomes were hospitalization for heart failure, a composite kidney outcome of end-stage kidney disease/kidney failure/need for dialysis and worsening of CKD stage from baseline. The effects of the intercurrent events of a sustained post-baseline decline in eGFR ≥ 30%, ≥ 40%, and ≥ 57% on the subsequent risk of the primary outcomes were also assessed.ResultsIn the main study cohort (N = 504,924), median age was 75.0 years, and 60.5% were female. Most patients (94.7%) had stage 3 CKD at index. Incidence rates for hospitalization for heart failure, the composite kidney outcome, and worsening of CKD stage from baseline were 4.0, 10.3, and 4.4 events/100 patient-years, respectively. The intercurrent event analysis demonstrated that a relative decline in kidney function from baseline significantly increased the risk of cardiorenal events.ConclusionsThis real-world study highlights that patients with non-diabetic CKD are at high risk of serious adverse clinical outcomes, and that this risk is amplified in patients who experienced greater post-baseline eGFR decline.Graphical abstract

Systemic Corticosteroid Use for COVID-19 in US Outpatient Settings From April 2020 to August 2021

This study uses 2 large US health care claims databases (Medicare fee-for-service and the US Food and Drug Administration’s Sentinel System) to examine systemic corticosteroid use among nonhospitalized patients with COVID-19.

Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019.

Light-chain (AL) amyloidosis is a multisystem disorder with a high early mortality and diagnostic delays of >1year from symptom onset. This retrospective observational study sought to characterize the clinical prodrome and diagnostic delay to inform early detection. We identified 1523 adults with newly diagnosed AL amyloidosis in the Optum de-identified Clinformatics® Datamart US healthcare claims database as those with ≥2 new diagnosis codes for AL or other amyloidosis in 90days with ≥1 multiple myeloma treatment within 730days, excluding patients with prior hereditary or secondary amyloidosis and Familial Mediterranean Fever. We considered 34 signs/symptoms using diagnosis codes in all observable time on or before AL amyloidosis diagnosis. Sign/symptom prevalence was compared to that of 1:4 matched population controls. The overlap and sequence of signs/symptoms and the median time from first sign/symptom to AL amyloidosis diagnosis were explored. Healthcare utilization was summarized. The most common individual AL amyloidosis signs/symptoms were malaise/fatigue (61%) and dyspnea (59%). Cardiac signs/symptoms were observed in 77% of patients, followed by renal (62%) and neurologic (59%) signs/symptoms. Multisystem involvement (≥3 systems) was present in 54%. Monoclonal gammopathy was detected in 29% before diagnosis. Median time from symptom onset to AL amyloidosis diagnosis was 2.7years. Healthcare utilization was high between first AL amyloidosis signs/symptoms and diagnosis, with 50% visiting ≥5 physician types. AL amyloidosis patients have a lengthy and complex clinical prodrome. Novel approaches to early diagnosis are needed to improve outcomes.

Characteristics of Treated Asthmatics Experiencing Exacerbations in a US Database: A Retrospective Cohort Study.

RationaleThe National Heart, Lung, and Blood Institute (NHLBI) recommend a stepwise approach to asthma management, with the goals of maintaining asthma control and reducing exacerbations. Although asthma treatments reduce the frequency of exacerbations, they still occur. We aimed to characterize the treated United States of America (US) adult asthma population, including those experiencing exacerbations, in terms of socio-demographics, clinical characteristics, and healthcare resource utilization (HRU).Patients and MethodsA retrospective cohort of asthma patients aged ≥18 years on 01 January 2014 with ≥1 ICD-9 asthma code (493.xx) enrolled in a US healthcare claims database during 2013–2014. Patients who had ≥2 asthma medication dispensings during 2013 (baseline), including ≥1 in the 90-day period before index date, were classified according to NHLBI step. Patients with chronic obstructive pulmonary disease, cystic fibrosis, or lung cancer diagnoses were excluded. Demographics, comorbidities, clinical characteristics, and HRU were described during baseline. Exacerbations and HRU were described during 2014 (follow-up period).ResultsIn total, 72,156 patients were included; 10,590 (14.7%) had ≥1 exacerbation during follow-up. Approximately 44% of patients were classified as NHLBI Steps 1–2, 41% as Steps 3–4, and 11% as Steps 5–6. Exacerbation frequency increased with step (Steps 1, 2, and 3: 12–14%; Steps 4, 5, and 6: 16–26%). Compared with the overall population during baseline, patients with an exacerbation had similar demographics, but differences were observed for comorbid allergic rhinitis (46.4% vs 40.1%, respectively), blood eosinophil counts ≥300 cells/μL (45.5% vs 39.6%, respectively), and asthma-related healthcare encounters (62.9% vs 52.4%, respectively). Overall, asthma-related HRU during follow-up increased with NHLBI step.ConclusionExacerbations were observed among patients classified at each NHLBI step and were more frequent with increasing step. Exacerbations and asthma-related HRU highlight the continued unmet need in the treated US asthma population.

Real-World Occurrence of Symptoms and Toxicities and Associated Cost Implications in Acute Myeloid Leukemia (AML) Treatment Episodes: A Retrospective Database Analysis in the US

Background:There is a lack of published estimates of the occurrence of major symptoms and toxicities (SxTox events) and associated costs during AML episodes of care in real-world data. This analysis evaluated the frequency and cost implication of SxTox events in a US commercially insured population with AML during these episodes of care: high intensity chemotherapy (HIC), low intensity chemotherapy (LIC), hematopoietic stem cell transplant (HSCT) and relapsed-refractory (R/R) treatment.Methods:A large US healthcare claims database (PharMetrics Plus™) was linked to charge detail master (CDM) hospital data, to identify incident adult patients (≥ 2 outpatient or ≥ 1 inpatient claim with an AML diagnosis) between 1/1/2008 and 3/31/2016. Patients had continuous health plan enrolment for ≥ 6 months pre and ≥ 3 months post the first diagnosis date (index) to assure collection of representative data. Episodes evaluated included HIC induction (inpatient high dose cytarabine+anthracycline use within 3 months post-index), HIC consolidation (cytarabine +/- anthracycline use within 2 months following a prior HIC), LIC (receipt of low-intensity or less toxic chemotherapy in the outpatient setting within 3 months post-index), HSCT (a record of transplant specific diagnosis/procedure codes) and R/R patients (ICD-9 diagnosis code of 205.02 for relapsed AML, or a new line of therapy (new agent or re-initiation of treatment after 90-day gap), after a prior treatment of HIC, LIC, or HSCT). SxTox events of interest observed during episodes were identified via diagnostic and treatment codes and reported as frequencies. A generalized linear model (GLM) was used to assess the contribution of events to total episode costs while controlling for age, gender and Charlson Comorbidity Index (CCI) score.Results:The study sample consisted of 1,542 HIC induction (mean age 47.0 years; mean follow-up 2.1 months), 591 consolidation (mean age 47.0 years; mean follow-up 1.5 months), 628 LIC (mean age 64.9 years; mean follow-up 2.0 months), 1,000 HSCT (mean age 51.4 years; mean follow-up 6.4 months) and 910 R/R patients (mean age 52.3 years; mean follow-up 12.6 months). The SxTox events most frequently observed during HIC induction episodes were blood and lymphatic system disorders (98.8%), infections (91.1%), gastrointestinal (GI) disorders (69.1%), nervous system disorders (56.2%), cardiovascular (CV) disorders (44.6%), bleeding (39.0%), and skin and subcutaneous tissue disorders (31.2%). Most HIC consolidation patients experienced blood and lymphatic system disorders (96.4%) and infections (89.5%); while other SxTox events were less frequent except bleeding event rates were higher (73.6%) than during induction (Table 1). LIC patients experienced lower rates of SxTox events compared to HIC induction; frequently observed events were blood and lymphatic system disorders (84.1%), infections (64.3%), bleeding (54.0%), GI (47.5%), CV (36.5%), and renal disorders (27.9%). HSCT patients had similar SxTox event rates as those occurring during HIC induction, while the following SxTox events were more frequent: GI disorders, bleeding events, renal, and CV disorders. R/R patients had a higher occurrence and wider range of high frequency SxTox events, including blood and lymphatic system disorders (96.8%), infections (96.4%), GI disorders (83.2%) bleeding (68.9%), CV disorders (67.5%), nervous system disorders (62.7%), skin and subcutaneous tissue disorders (36.6%), renal disorders (35.6%), and vascular disorders (31.5%). Multivariate GLM results revealed that R/R episodes were sensitive to the occurrence of any SxTox events, which significantly increased costs during R/R episodes, while the occurrence of SxTox events had a mixed impact on increasing total costs in other episodes. CV disorders consistently increased total costs in the following episodes: HIC induction (22% higher; p<0.001), consolidation (23% higher; p=0.005), LIC (36% higher; p<0.001), and R/R episodes (32% higher; p<0.001).Conclusions:This analysis observed that major symptoms and toxicities are associated with a significant clinical and economic burden during AML treatment episodes in the US. These SxTox events had the broadest impact on R/R AML patients which may suggest R/R AML patients are less tolerant of currently available treatments. Therapies with lower toxicity would fill an unmet need, especially in R/R AML. [Display omitted] DisclosuresPandya:Astellas Pharma Global Development: Employment. Chen:QuintilesIMS: Employment. Wilson:Astellas Pharma Global Development: Employment. Groves:QuintilesIMS: Employment. Horvath:Astellas Pharma Global Development: Employment. Wade:QuintilesIMS: Employment.