Risk factors for severe COVID-19 among patients with systemic lupus erythematosus: a real-world analysis of a large representative US administrative claims database, 2020-2021.

OBJECTIVES: To identify risk factors for progression to severe COVID-19 and estimate the odds of severe COVID-19 associated with vaccination among patients with systemic lupus erythematosus (SLE). METHODS: This retrospective cohort study identified adults with SLE in the Merative™ MarketScan® Databases. Patients were continuously enrolled the year before 1 April 2020 (baseline) and had a COVID-19 diagnosis between 1 April 2020 and the earliest of death, enrolment end or 31 December 2021. Severe COVID-19 was defined as hospitalisation with a COVID-19 diagnosis. Demographics on 1 April 2020, baseline comorbidities, corticosteroid use ≤30 days before COVID-19 diagnosis and other SLE medication use ≤6 months before COVID-19 diagnosis were assessed. Vaccination was identified by claims for a COVID-19 vaccine or vaccine administration. Backward stepwise logistic regression estimated odds of progression to severe COVID-19 associated with patient characteristics and vaccination. RESULTS: Among 2890 patients with SLE with COVID-19, 500 (16.4%) had a COVID-19-related hospitalisation. Significant risk factors for progression to severe COVID-19 included rituximab (OR (95% CI) 2.92 (1.67 to 5.12)), renal failure (2.15 (95% CI 1.56 to 2.97)), Medicaid (vs Commercial; 2.01 (95% CI 1.58 to 2.57)), complicated hypertension (1.96 (95% CI 1.38 to 2.77)) and time of infection, among others. Vaccination had a significant protective effect (0.68(95% CI 0.54 to 0.87)) among all patients with SLE with COVID-19, but the effect was not significant among those with prior use of belimumab, rituximab or corticosteroids. CONCLUSIONS: Certain chronic comorbidities and SLE medications increase the odds of progression to severe COVID-19 among patients with SLE, but vaccination confers significant protection. Vaccine effectiveness may be attenuated by SLE treatments. Protective measures such as pre-exposure prophylaxis and booster vaccines should be encouraged among patients with SLE.

Comparing the burden of illness in patients with alopecia areata vs atopic dermatitis in the US population from a payer perspective.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. AA frequently co-occurs with other inflammatory autoimmune conditions, presenting a significant clinical burden. OBJECTIVE: To compare the burden of illness, direct and indirect costs in adult patients with AA vs atopic dermatitis (AD). METHODS: This retrospective cohort study used US administrative claims data from the Merative MarketScan Commercial Claims and Encounters Database to compare commercially insured adults with AA to those with AD. Patients with an AA diagnosis between January 2017 and September 2019 were propensity score matched to patients with AD. Comorbidity burden, medication use, health care resource utilization, health care costs, and indirect costs during a 12-month follow-up period were compared between cohorts. RESULTS: Overall, 25,446 adult patients with AA were selected for the matched analysis with the AD cohort. Patients with AA generally had lower comorbidity burden than patients with AD; mean Deyo-Charlson Comorbidity Index scores were 0.36 (SD = 0.99) and 0.39 (SD = 0.92), for AA and AD, respectively (P = 0.007). Patients with AA had significantly lower proportions of allergic rhinitis, asthma, pruritus, skin infections, and urticaria, but higher proportions of thyroid disease, when compared with patients with AD (all P < 0.001). A smaller proportion of patients with AA had prescriptions for topical (45.3% vs 64.8%; P < 0.001) and oral (20.3% vs 29.6%; P < 0.001) corticosteroids and antianxiety and/or antidepressants (24.7% vs 29.7%; P < 0.001), but a significantly larger proportion for intralesional corticosteroids (triamcinolone) (49.6% vs 21.7%; P < 0.001), compared with patients with AD. Despite a lower comorbidity burden and generally less medication usage in patients with AA, total all-cause health care costs did not significantly differ between the AA and AD cohorts ($10,705 vs $10,816; P = 0.712), and outpatient costs were higher in patients with AA ($6,297 vs $5,859; P = 0.014). Female patients with AA had significantly greater costs for both outpatient and outpatient pharmacy when compared with female patients with AD. Patients with AA were more likely to have a claim for long-term disability (0.6% vs 0.3%; P = 0.001) and higher long-term disability-associated indirect costs ($73 [SD = $1,442] vs $25 [SD = $774]; P = 0.004) compared with patients with AD. CONCLUSIONS: We found similar total health care costs in patients with AA and AD, despite a lower proportion of comorbidities and prescription use in patients with AA. Outpatient costs were also significantly higher overall in patients with AA. Although often dismissed as a cosmetic condition, AA, an autoimmune disease, has a similar level of medical expenditure as AD. DISCLOSURES: This study was funded by Eli Lilly and Company. Mr Fenske and Drs Ding, Morrow, and Smith are employed by Eli Lilly and Company. Drs Manjelievskaia, Moynihan, and Silver are employed by Merative. Drs Manjelievskaia, Moynihan, and Silver were employed by IBM Watson Health at the time of study completion. IBM Watson Health received funding from Eli Lilly and Company to conduct this study.

Clinical and economic burden of uncontrolled severe noneosinophilic asthma.

OBJECTIVES: To quantify the clinical and economic burden of patients with severe asthma with low blood eosinophil counts (BECs) untreated with biologics. STUDY DESIGN: Retrospective cohort study in IBM MarketScan claims database. METHODS: Patients 12 years and older with severe asthma with BEC data were selected between January 1, 2013, and June 30, 2018 (date of the most recent BEC was used as the index date). Inclusion criteria were (1) presence of BEC laboratory test result, (2) continuous enrollment for 12 months preceding and following the index date, (3) meeting the Healthcare Effectiveness Data and Information Set definition of persistent asthma, (4) meeting the Global Initiative for Asthma definition of severe asthma, and (5) an absence of biologic treatment, other respiratory diagnoses, and malignancies 12 months preceding and following the index date. Asthma exacerbations, levels of disease control, and all-cause and asthma-related health care costs were reported during the 12-month postindex period for patients with a BEC less than 300 cells/mcL. RESULTS: The sample included 8073 patients with severe asthma; 78% (n = 6260) presented with a BEC less than 300 cells/mcL. Mean (SD) age of the sample was 54.8 (14.2) years; 64% were female. Eighteen percent of patients had an asthma exacerbation; 19% had either uncontrolled or suboptimally controlled asthma based on the frequency of asthma-related hospital admissions, emergency department visits, or corticosteroid prescription fills. One-year all-cause and asthma-related total health care costs were $25,845 and $2802, respectively. Patients with suboptimally controlled and uncontrolled asthma spent $1471 and $3872 more, respectively, on asthma-related claims compared with patients with controlled asthma. CONCLUSIONS: Among patients with severe asthma with low eosinophils untreated with biologics, there is a high burden of disease among those who have suboptimal disease control, highlighting an unmet need in severe asthma treatment.

Costs of treatment change following first-line somatostatin analog monotherapy among patients with neuroendocrine tumors.

BACKGROUND: This study describes treatment characteristics and healthcare costs prior to and following treatment change from somatostatin analog (SSA) monotherapy among a privately-insured NET patient population in the US. METHODS: Patients with newly diagnosed NET and treated with SSA monotherapy were retrospectively identified in IBM MarketScan claims between 1/1/2014 and 3/31/2019. NET treatment change was captured ≥30 days after the SSA start date (earliest new treatment = index date). Healthcare costs (reimbursed amount in 2019 dollars) were reported for 1, 3, and 6 months pre- and post-index intervals. RESULTS: A total of 305 patients were identified (mean age: 58 years; female: 52%; metastatic disease: 49%). Most patients started on octreotide (81%) vs. lanreotide (19%). Common treatment changes included alternate SSA (38%), targeted therapy (30%), or chemotherapy (23%). Total costs increased on average by $13,272 between the month preceding and following treatment change (p < .001), with the highest increase among patients changing to targeted therapy ($19,677, p < .001) vs. an alternate SSA ($10,240, p < .001) or chemotherapy ($4,057, p = .155). The trajectory in mean cost difference using a 1, 3, and 6-month time period followed an increasing trend for patients who changed to targeted therapy (Δ$19,677, Δ$34,856, Δ$58,387) but was flat for patients who changed to the alternate SSA (Δ$10,240, Δ$10,026, Δ$11,727). CONCLUSIONS: Higher total healthcare costs were observed following treatment change from first-line SSA. Switching to the alternate SSA was associated with a fixed, one-time cost; whereas, switching to targeted therapy was associated with both an initial switching cost and a persistent monthly increase.

Exploration of machine learning techniques to examine the journey to neuroendocrine tumor diagnosis with real-world data.

Aim: Machine learning reveals pathways to neuroendocrine tumor (NET) diagnosis. Patients & methods: Patients with NET and age-/gender-matched non-NET controls were retrospectively selected from MarketScan claims. Predictors (e.g., procedures, symptoms, conditions for which NET is misdiagnosed) were examined during a 5-year pre-period to understand presence of and time to NET diagnosis using conditional inference trees. Results: Among 3460 patients with NET, 70% had a prior misdiagnosis. 10,370 controls were included. Decision trees revealed combinations of factors associated with a high probability of being a patient with NET (e.g., abdominal pain, an endoscopic/biopsy procedure, vomiting) or longer times to diagnosis (e.g., asthma diagnosis with visits to >6 providers). Conclusion: Decision trees provided a unique examination of the journey to NET diagnosis.

Lay abstract We present the novel analytic approach of machine learning using real-world data to describe patient pathways to neuroendocrine tumor (NET) diagnosis. Due to the rarity and presentation of the disease, NET diagnosis is commonly inaccurate and delayed. We aimed to demonstrate the potential of analytics using conditional inference trees. Decision trees revealed specific combinations of characteristics associated with a high probability of being a patient with NET (e.g., abdominal pain, an endoscopic/biopsy procedure, vomiting) or longer times to diagnosis (e.g., asthma diagnosis with visits to >6 providers). Results from this study support prior literature and add advanced analyses that take initial steps toward developing tools aimed to help clinicians with early and accurate NET diagnosis. The methodology can be improved upon and translated to other diseases.

Clinical and economic burden of severe asthma among US patients treated with biologic therapies.

BACKGROUND: Patients with severe asthma may remain uncontrolled despite biologic therapy in addition to standard therapy, but this disease burden has not been quantified. OBJECTIVE: To estimate the clinical and economic burden in a US national sample. METHODS: Patients who have severe asthma with indicated biologic treatment (earliest use = index date) were selected from the MarketScan database between January 1, 2013, and June 30, 2018. Inclusion criteria were continuous enrollment for 12 months postindex with a minimum of 2 biologic fills, greater than or equal to 12 years of age, evidence of medium- to high-dose inhaled corticosteroids and long-acting ß-agonist combination before the index, and absence of other respiratory diagnoses and malignancies. Disease exacerbations (used to classify asthma control), health care costs, and treatment characteristics were reported during the 12-month postindex period. RESULTS: The sample included 3262 biologic patients; 88% with anti-immunoglobulin E therapy (omalizumab) and 12% non-anti-immunoglobulin E (reslizumab, mepolizumab, benralizumab). The mean age was 49 (±15) years; 64% were women. Prescriptions included inhaled corticosteroids and long-acting ß-agonist (82%), systemic corticosteroids (76%), and leukotriene receptor antagonists (68%). Notably, 63% of patients presented greater than or equal to 1 asthma exacerbation (mean 1.3 per patient/year). Furthermore, 35% of patients were categorized as having controlled asthma, whereas 28% were suboptimally controlled and 29% were uncontrolled. Patients with uncontrolled disease had higher all-cause and asthma-related costs ($69,206 and $45,693, respectively) than patients with suboptimally controlled ($59,407 and $40,793, respectively) or controlled disease ($53,083 and $38,393, respectively). Furthermore, 62% of newly treated patients were persistent with their index biologic. CONCLUSION: Biologic therapies are effective in reducing exacerbations, but a substantial proportion of patients with severe asthma treated with current biologics continue to experience uncontrolled disease, highlighting a remaining unmet need for patients with severe uncontrolled asthma.

Real-world impact of brain metastases on healthcare utilization and costs in patients with non-small cell lung cancer treated with EGFR-TKIs in the US.

BACKGROUND: Non-small cell lung cancer (NSCLC) with brain metastases (BM) is difficult to treat and associated with poor survival. This study assessed the impact of BM on healthcare-related utilization and costs (HRUC) among patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Adults newly-diagnosed with metastatic NSCLC, initiating first-/second-generation EGFR-TKI treatment, with BM or no BM (NBM), were identified retrospectively from IBM MarketScan healthcare claims databases (2013-2017). HRUC were measured during the variable-length follow-up period. Generalized linear models assessed the impact of BM on total healthcare costs, standardized to 2017 US$. RESULTS: Overall, 222 BM and 280 NBM patients were included, with a mean duration of follow-up of 14 months. Adjusted NSCLC-related and all-cause costs over average follow-up were 1.2 times higher among BM patients (Δ$5,640 and Δ$6,366, respectively; p <0.05); differences were driven primarily by radiation treatment and radiology. More than two times more BM than NBM patients received NSCLC-related radiation treatment, in both inpatient (15.3% vs 6.8%; p <0.05) and outpatient settings (87.8% vs 37.5%; p <0.05). Per-patient per-month (PPPM) radiation costs were also higher among BM patients, both inpatient ($796 vs $464, p =0.172) and outpatient ($2,443 vs $747, p <0.05). All-cause PPPM radiology visits (2.0 vs 1.3) and associated costs ($3,824 vs $1,621) were higher among BM patients (both p <0.05). CONCLUSION: NSCLC-related HRUC, especially those attributable to radiation treatment, were higher among patients with BM. Future research should compare the potential for CNS-active EGFR-TKIs vs first-/second-generation EGFR-TKIs combined with radiotherapy to reduce HRUC.

Real-world Comorbidity Burden, Health Care Utilization, and Costs of Nonalcoholic Steatohepatitis Patients With Advanced Liver Diseases.

GOALS: This study evaluates the real-world comorbidity burden, health care resource utilization (HRU), and costs among nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients with advanced liver diseases [compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplantation (LT), hepatocellular carcinoma (HCC)]. BACKGROUND: NAFLD/NASH is a leading cause of liver diseases. MATERIALS AND METHODS: Adult NAFLD/NASH patients were identified retrospectively from MarketScan Commercial claims (2006-2016). Following initial NAFLD/NASH diagnosis, advanced liver diseases were identified using the first diagnosis as their index date. Mean annual all-cause HRU and costs (2016 USD) were reported. Adjusted costs were estimated through generalized linear models. Cumulative costs were illustrated for patient subsets with variable follow-up for each stage. RESULTS: Within the database, 485,774 NAFLD/NASH patients met eligibility criteria. Of these, 93.4% (453,564) were NAFLD/NASH patients without advanced liver diseases, 1.6% (7665) with CC, 3.3% (15,833) with DCC, 0.1% (696) with LT, and 0.1% (428) with HCC. Comorbidity burden was high and increased as patients progressed through liver disease severity stages. Compared with NAFLD/NASH without advanced liver diseases (adjusted costs: $23,860), the annual cost of CC, DCC, LT, and HCC were 1.22, 5.64, 8.27, and 4.09 times higher [adjusted costs: $29,078, $134,448, $197,392, and $97,563 (P<0.0001)]. Inpatient admissions significantly drove increasing HRU. CONCLUSION: Study findings suggest the need for early identification and effective management of NAFLD/NASH patients to minimize comorbidity burden, HRU, and costs in the privately insured US population.

Matched cohort study of healthcare resource utilization and costs in young children of mothers with postpartum depression in the United States.

Objective: To assess healthcare resource utilization (HRU) and costs in children of mothers with and without postpartum depression (PPD).Methods: Administrative claims data from the IBM Watson Health MarketScan Databases (2010-2016) were used. Women with live births (index date = delivery date) were identified and linked to their newborns. The mother-child pairs were divided into PPD and non-PPD exposure cohorts based on claims for depression, mood or adjustment disorders, or anxiety identified in the mother between 15 and 365 days after delivery. Mother-child pairs with PPD exposure were propensity score matched 1:3 to mother-child pairs without PPD exposure. Children were required to have 24 months of continuous health plan enrolment following delivery. Additional comparisons were performed between mother-child pairs with and without preterm delivery.Results: Overall, 33,314 mother-child pairs with PPD exposure were propensity score matched to 102,364 mother-child pairs without PPD exposure. During the 24-month follow-up period, HRU across most service categories was significantly higher among children in the PPD exposure cohort than non-PPD exposure cohort. Among outpatient services, the percentages of children with a physician specialist service (68% versus 64%), early-intervention screening (40% versus 37%), and an emergency room visit (48% versus 42%) were greater in children of mothers with PPD (all p < .001). Furthermore, children of mothers with PPD incurred 12% higher total healthcare costs in the first 24 months of life compared to children of mothers without PPD ($24,572 versus $21,946; p < .001). After excluding mothers with preterm delivery, the proportion of children with ER visits, physician specialist services, and outpatient pharmacy claims was significantly higher in the PPD exposure cohort than non-PPD exposure cohort (all p < .001).Conclusion: The results of this analysis suggest that HRU and costs over the first 24 months of life in children of mothers with PPD exceeded that of children of mothers without evidence of PPD.

Prenatal Cadmium Exposure Is Negatively Associated With Adiposity in Girls Not Boys During Adolescence.

Introduction: Cadmium is a pervasive toxic metal that remains a public health concern and exposure in early life has been associated with growth deficits in infancy and childhood. Growth during adolescence also may be sensitive to effects of cadmium exposure, given the changes in distribution of lean and adipose tissue that vary by sex during puberty. This study examines whether prenatal and concurrent cadmium exposures are associated with adiposity measures at ages 8-15 years in a well-characterized birth cohort. Methods: The sample included 185 participants from the ELEMENT birth cohorts in Mexico City with complete data on urinary cadmium exposures, anthropometry and covariates [child age and sex, household socioeconomic status, and maternal smoking history and body mass index (BMI)]. Maternal third trimester and adolescent urines were analyzed for cadmium using an Inductively Coupled Plasma Mass Spectrometer. Trained personnel obtained anthropometry including height, weight, waist circumference and subscapular, suprailiac, and triceps skinfold thickness. BMI z-scores for age and sex were calculated using the World Health Organization's reference standard. Linear regression models were used to estimate the association of prenatal and concurrent urinary cadmium levels with adolescent anthropometry, adjusting for covariates. Results: Among 87 males and 98 females, median age was 10 years (IQR 9 -11 years). Pregnant women and children had median urinary cadmium concentrations of 0.19 µg/L (IQR 0.12- 0.27 µg/L) and 0.14 µg/L (IQR 0.11- 0.18 µg/L), respectively. Regression models showed inverse relationships between prenatal cadmium exposure and adolescent adiposity. An IQR increase in prenatal cadmium was associated with percent decreases in BMI z-score (-27%, p = 0.01), waist circumference (-3%, p = 0.01), and subscapular (-11%, p = 0.01), suprailiac (-11%, p = 0.02), and triceps (-8%, p < 0.01) skinfold thickness. When stratified by sex, these relationships remained statistically significant in females but not males. Conclusions: Prenatal cadmium exposure was negatively associated with measures of both abdominal and peripheral adiposity in girls, but not in boys. These results emphasize the sex-dependent effects of in utero cadmium exposure on adiposity in adolescence.

Dietary predictors of urinary cadmium among pregnant women and children.

BACKGROUND: Cadmium is a toxic metal with modifiable exposure sources including diet. In pregnant women and children, unique dietary habits may contribute to DCd, and the relationship of diet to overall cadmium exposure can depend on specific factors during these transitional time periods. OBJECTIVES: This study aimed to identify and quantify food sources of DCd, describe the distribution of UCd, and determine the relationship of DCd and intake of specific foods with UCd, stratified by maternal smoking history, among pregnant women and children in a well-characterized Mexico City birth cohort. METHODS: Our sample included 192 pregnant women (third trimester) and 223 children (7-15years). DCd was calculated using FFQ and the U.S. TDS. We also measured UCd, maternal history of smoking, and additional covariates. RESULTS: Pregnant women and children had geometric mean UCd concentrations of 0.19±0.78µg/L and 0.14±0.60µg/L, respectively. On average, estimated daily DCd intake was 9.3±3.5µg for women and 12.2±5.4µg for children. Adjusted linear regression models showed a positive association between DCd and UCd among women (p=0.03) and children (p=0.03) without a maternal history of smoking. Intake of fruit and vegetables among women and potato consumption among children were positively associated with UCd. CONCLUSIONS: Pregnant women and their children are exposed to cadmium at dietary and urinary levels similar to those previously reported. Higher estimated DCd for children than for women could be attributed to the different FFQs or related to dietary pattern changes between age groups. DCd contributed to UCd in those without a maternal smoking history.

Trans-fatty acids in cooking oils in Bogota, Colombia: changes in the food supply from 2008 to 2013.

OBJECTIVE: Long-chain n-3 fatty acid intake in Colombia is low because fish consumption is limited. Vegetable oils with high n-3 fatty acid content are recommended, but their concentrations of trans fats were high in previous studies. Thus, regular monitoring of the fatty acid composition of vegetable oils is required. Our objective was to quantify the fatty acid composition in commercially available oils in Bogota, Colombia and determine if composition changed from 2008 to 2013. DESIGN: Cross-sectional study. We obtained samples of all commercially available oils reported in a survey of low- and middle-income families with a child participating in the Bogota School Children Cohort. SETTING: Bogota, Colombia. SUBJECTS: Not applicable. RESULTS: Sunflower oil had the highest trans-fatty acid content (2.18%). Canola oil had the lowest proportion of trans-fatty acids (0.40%) and the highest n-3 fatty acid content (9.37%). In terms of percentage reduction from 2008 to 2013 in 18:1 and 18:2 trans-fatty acids, canola oil had 89% and 65% reduction, mixed oils had 44% and 48% reduction, and sunflower oil had 25% and 51 % reduction, respectively. Soyabean oil became widely available in 2013. CONCLUSIONS: The content of trans-fatty acids decreased in all oils from 2008 to 2013, suggesting a voluntary reduction by industry. We believe that regular monitoring of the fatty acid composition of oils is warranted.