Post-index Date Research Articles

Real-World Treatment Patterns and Outcomes in Patients with Hemophagocytic Lymphohistiocytosis (HLH) and Other Clinical Conditions Treated with Emapalumab: The Real-HLH Study Design

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by overactivation of the immune system due to systemic release of proinflammatory cytokines, especially of interferon gamma (IFNγ), and persistent activation of macrophages/histiocytes and T cells. Emapalumab, a fully human, anti-IFNγ monoclonal antibody that binds to both free and receptor-bound IFNy, neutralizing its biologic activity, was approved by the Food and Drug Administration (FDA) in 2018 for the treatment of adult and pediatric patients with primary HLH with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. The safety and efficacy of emapalumab was based on results from a pivotal phase 2/3 trial which reported a 63% overall response in patients treated with emapalumab. Since approval, no study has evaluated the use of emapalumab in a larger cohort of patients in the real-world clinical setting.Aim: To assess real-world treatment patterns and outcomes, clinical and demographic characteristics among patients treated with emapalumab.Method: This retrospective, non-interventional, observational medical chart review study will include patients treated across treatment centers in the US with emapalumab in a non-clinical trial setting. The study aims to include more than 100 patients who have been treated with at least one dose of emapalumab between November 20, 2018 and December 31, 2020 (patient identification period). The date that the patient initiates treatment with emapalumab within the patient identification period is defined as the index date. The post-index date is defined as the period from the index date through to the study end date (June 30, 2021), end of data availability for the patient, or date of death, whichever occurs first. Patients will be classified into three groups (i.e. primary HLH, secondary HLH, or non-HLH) based on the information obtained from their charts, the HLH 2004 diagnostic criteria, and adjudication by the REAL-HLH Steering Committee.Results: The primary objective of the study is to describe treatment patterns in patients with HLH treated with emapalumab in a real-world clinical setting, including emapalumab dose, treatment duration, and reasons for initiating or discontinuing treatment. The secondary objectives are to describe demographic and clinical characteristics of patients with HLH treated with emapalumab, and their outcomes. The exploratory objectives include detailing the demographic, clinical characteristics, treatment patterns, and outcomes of patients with non-HLH clinical conditions treated with emapalumab (Table 1). Demographics and clinical characteristics will be analyzed at the time of diagnosis. Treatment patterns and outcomes will be analyzed during the post-index date.Conclusion: The study aims to assess treatment patterns and outcomes, clinical and demographic characteristics among patients treated with emapalumab, a novel IFNγ blocking agent, in real-world clinical settings in the US. [Display omitted] DisclosuresAllen: Sobi: Consultancy. Leiding: Sobi: Consultancy. Chandrakasan: Sobi: Consultancy. Walkovich: X4 Pharmaceuticals: Other: Local PI for clinical trial involving mavorixafor and patients with neutropenia; Swedish Orphan Biovitrum AB (Sobi): Consultancy, Honoraria; Pharming: Honoraria, Membership on an entity's Board of Directors or advisory committees; Horizon Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oladapo: Sobi: Current Employment. Yee: Sobi: Current Employment. Pednekar: Sobi: Consultancy; PRECISIONheor: Current Employment. Raza: Sobi: Consultancy; PRECISIONheor: Current Employment. Jordan: Sobi: Consultancy.

Characteristics and Outcomes of COVID-19 Patients with Mature B-Cell Non-Hodgkin Lymphomas (mB-Cell NHL): A US Nationwide Electronic Health Record (EHR) Database Study

IntroductionCOVID-19 poses a serious concern for mB-cell NHL patients given their advanced age, high burden of comorbidities, and immune dysfunction. Limited by smaller sample sizes during the early period of the COVID-19 pandemic, previous studies were unable to thoroughly evaluate the impact of COVID-19 on patients with mB-cell NHL 1,2. We aim to describe demographics and clinical characteristics, outcomes, and risk factors associated with death and other severe outcomes among COVID-19 patients with mB-cell NHL in a large US nationwide database.MethodsThis retrospective cohort study was conducted using the Optum EHR database, comprising data from an integrated network of ambulatory and hospital care providers across the US. Patients with COVID-19 (diagnosis code of U07.1, U07.2, or a positive result of SARS-Cov-2 virus PCR or antigen tests) between Feb. 1, 2020 and Jan 7, 2021 (index date) and mB-cell NHL diagnosis prior to the COVID-19 diagnosis were included. Patients were excluded if they were under 18 years of age, had missing age or sex, or had <1year continuous eligibility prior to their index date (pre-index period). All baseline characteristics, including demographics and comorbidities, were determined during the one-year pre-index period. Severe outcomes, including death, hospitalization, ICU admission, and acute respiratory insufficiency (ARI), were evaluated within 30 days post-index date. Multivariable logistic regression was conducted to identify variables independently associated with severe outcomes.ResultsAmong 2,767 patients with mB-cell NHL who were infected with SARS-CoV-2 between Feb. 1, 2020 and Jan. 7, 2021 (mean age±SD: 67.9 years±14.7, 53.9% male), majority were white (73.9%), followed by African American (10.9%), Hispanic (6.9%), and Asian (1.2%). The most common subtypes of mB-cell NHL were chronic lymphocytic leukemia/small lymphocytic lymphoma (26.9%), multiple myeloma (22.4%), diffuse large B-cell lymphoma (13.2%), and follicular lymphoma (7.3%). Of these patients, 93.4% have at least one comorbidity. The most common comorbidities were hypertension (58.5%), neurological disease (49.4%), diabetes (28.2%), ischemic heart disease (25.5%), cardiac arrhythmia/conduction disorders (24.4%), chronic kidney disease (CKD, 19.2%), heart failure/cardiomyopathy (18.1%), and COPD (12.3%).Overall, 960 patients (34.7%) developed severe outcomes, among which, 847 patients (30.6%) were hospitalized, 214 patients (7.7%) were admitted to the ICU, 201 patients (7.3%) experienced ARI, and 220 patients (8.0%) died. Multivariable logistic regression showed that increased odds of severe outcomes were independently associated with older age (85+ years vs. <65 years; adjusted odds ratio [OR], 2.0; 95% CI, 1.4-2.7), male gender (OR, 1.4; 95% CI, 1.1-1.6), insurance coverage with Medicaid (OR, 1.8; 95% CI, 1.1-2.9) and/or Medicare (vs. commercial only; OR, 1.9; 95% CI, 1.5-2.5), infected during the first quarter (OR, 5.6; 95% CI, 3.4-9.4) or second quarter of 2020 (vs. fourth quarter of 2020; OR, 1.7; 95% CI, 1.4-2.1), having CKD (OR, 1.3; 95% CI, 1.0-1.6), COPD (OR, 1.4; 95% CI, 1.0-1.8), diabetes (OR, 1.3; 95% CI, 1.1-1.6), and receiving active treatment for NHL (OR, 1.4; 95% CI, 1.0-2.0) within 30 days prior to COVID-19 diagnosis (Figure).ConclusionsThis study demonstrated key demographic and clinical characteristics associated with severe outcomes among COVID-19 patients with mB-cell NHL using one of the largest nationwide databases. Risk factors for severe outcomes identified in the general population, such as older age, male gender, and having certain underlying medical conditions were also identified in this study. In addition, COVID-19 infection occurring earlier in the pandemic and receiving active NHL treatments were associated with severe outcomes. These latter two observations might reflect the improvement in patient management during the latter period of the pandemic and that active mB-cell NHL disease and treatment rendered an increased risk of severe outcomes in COVID-19 patients with mB-cell NHL. These insights highlight the importance of utilizing demographic, clinical and treatment information to estimate the risk for severe outcomes, whereas prospective studies focusing on optimal COVID-19 management are required to identify specific actions that can be taken to improve outcomes of COVID-19 in patients with mB-cell NHL. [Display omitted] DisclosuresYue: Joule: Current Employment. Hallett: AbbVie: Current Employment. Liu: AbbVie: Current Employment. Iyengar: AbbVie: Current Employment. Basa: AbbVie: Current Employment. Yang: AbbVie: Current Employment.

Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Prevalence of type 2 inflammatory diseases in pediatric patients with atopic dermatitis: Real-world evidence

Patients with atopic dermatitis (AD) are considered at increased risk of developing other type 2 inflammatory diseases. However, real-world evidence based on large commercially insured pediatric populations in the United States is scarce. To use a large claims database (IBM MarketScan 2013-2017) in the United States to assess prevalence and incidence of type 2 inflammatory diseases in pediatric patients with AD. Pediatric patients with AD were matched 1:1 to patients without AD. Prevalence was assessed for conjunctivitis, rhinitis, urticaria, asthma, eosinophilic esophagitis, and chronic rhinosinusitis/nasal polyps at the 12months' post-index date (the first AD diagnosis date for patients with AD; a randomly selected outpatient visit for control patients). The incidence of other type 2 inflammatory diseases post-index was assessed among patients 0-2years of age. A total of 244,776 AD and matched non-AD patients were selected. The prevalence and incidence of type 2 inflammatory diseases were higher among patients with AD. Overall, the prevalence more than doubled for asthma, eosinophilic esophagitis, urticaria, and rhinitis, and increased with AD severity. AD identification was based on billing diagnoses; the observation period was only 12months; and the study was limited to commercially insured patients. The burden of type 2 inflammatory diseases in pediatric patients with AD is substantial, highlighting the need to optimize management of AD and its numerous associated morbidities.

Healthcare Costs Incurred by Patients with Multiple Myeloma Following Triple Class Exposure (TCE) in the US.

IntroductionMultiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody).MethodsAdult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009–February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date.ResultsA total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs.ConclusionIn this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40487-021-00175-z.

A Retrospective Analysis of Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults.

BackgroundClinicians use sex-based kidney function estimating equations, but the appropriate sex modifier for transgender adults undergoing hormone therapy (HT) is undetermined.ObjectivesCompare median estimated creatinine clearance (eCrCL; Cockcroft-Gault) and estimated glomerular filtration rates (eGFRs; Modification of Diet in Renal Disease [MDRD] and Chronic Kidney Disease Epidemiology Study [CKD-EPI]) before and during HT when estimated with and without sex assigned at birth.MethodsSingle-system retrospective cohort study of transgender adults (2007-2017) prescribed ≥90 days HT (index date = first order) and measured serum creatinine ≤6 months pre-index date (baseline) and ≤12 months post-index date. We grouped patients based on testosterone or estrogen treatment and compared eCrCL and eGFRs at baseline up to 6-12 months post-index date using equations based on sex assigned at birth (female or male modifier in testosterone or estrogen groups, respectively) or gender identity (male or female modifier in testosterone or estrogen groups, respectively). We used Wilcoxon signed-rank tests (Bonferroni correction) for all comparisons.ResultsIn total, 29 (median age 26 years, follow-up 259 days) and 41 patients (29 years, 250 days) were prescribed testosterone or estrogen, respectively. In the testosterone group, the maximum eCrCL and eGFR changes based on sex assigned at birth were −14%, P = 0.0181; −18%; P = 0.0009, respectively, and based on gender identity were +5%, P > 0.025 and +11%, P = 0.0094, respectively. In the estrogen group, eCrCL or eGFRs based on sex assigned at birth did not change from baseline but based on gender identity were −17%, P < 0.0001 and −26%, P < 0.0001, respectively.Conclusion and RelevanceFemale-based equations may underestimate kidney function in transgender adults undergoing testosterone or estrogen treatment. Prospective cohort studies are needed to confirm the clinical significance of these findings.

Wilson's Disease: An Analysis of Health Care Use and Cost Burden of Commercially Insured Adults in the United States.

The economic and health care use burdens of Wilson’s disease (WD) are unknown. In this study, we aimed to quantify this health care resource use and economic burden. We performed a retrospective case‐control analysis of individuals in the Truven Health MarketScan Commercial Claims database (2007‐2017). Using propensity scores, 424 WD cases were matched 1:1 to chronic liver disease (CLD) controls without WD. Total and service‐specific parameters, expressed in monthly averages, were quantified for the 6‐month pre‐WD diagnosis versus the 12‐month period after diagnosis. Wilcoxon signed‐rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare health care burdens. Relative to the 6‐month pre‐WD diagnosis, the 12 months after diagnosis had more claims per patient (2.87 vs. 3.35; P < 0.0001) and increased per patient health care costs (US $2,089 vs. US $3,887; P < 0.0001). WD cases incurred US $1,908 more in total unadjusted costs compared to controls in the 12‐month postindex date monthly averages. The increase in claims was primarily due to outpatient visits (1.62 vs. 1.82) and pharmaceutical claims (1.11 vs. 1.37). Cases also had higher health care costs for inpatient admissions (US $559 vs. US $1,264), outpatient visits (US $770 vs. US $1,037), and pharmaceutical claims (US $686 vs. US $1,489). Conclusion: WD is associated with significant health care cost and use burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

The use of mono- and combination drug therapy in men and women with lower urinary tract symptoms (LUTS) in the UK: a retrospective observational study

BackgroundCombination drug therapy for lower urinary tract symptoms (LUTS) is beneficial to selected patients and recommended by guidelines. Patterns of real-world LUTS drug use, especially combination drug therapy, have not been studied extensively. Moreover, further understanding of the recent landscape is required following the introduction of the beta-3-adrenoceptor agonist mirabegron in the UK in 2013 for overactive bladder (OAB). The objective was to describe mono- and combination drug therapy use for LUTS in patients in UK clinical practice.MethodsThis was a retrospective, descriptive, observational database study using UK Clinical Practice Research Datalink GOLD and linked databases. Men and women ≥ 18 years with a first prescription for any LUTS drug from 2014 to 2016 with ≥ 12 months continuous enrollment pre- and post-index date were included. Primary endpoints were mono- or combination drug therapy use for LUTS in male and female cohorts. Secondary endpoints were description of treatment prescribed, treatment persistence and patient demographics. Data were analyzed descriptively. Sub-cohorts were defined by drugs prescribed at index date.Results79,472 patients (61.3% male) were included, based on index treatments. Of all men, 82.5% received any benign prostatic obstruction (BPO) drug, 25.4% any OAB drug, and 7.9% any BPO drug plus any OAB drug. As either mono- or combination drug therapy, 77.1% received an alpha-blocker, 18.9% a 5-alpha reductase inhibitor, 23.9% an antimuscarinic agent, and 2.1% mirabegron. Of all women, 94.5% received any OAB drug, 6.0% duloxetine, and 0.5% any OAB drug plus duloxetine. As either mono- or combination drug therapy, 87.7% received an antimuscarinic, and 9.7% mirabegron. In men or women receiving OAB treatment, approximately 2.5% received combination drug therapy with an antimuscarinic agent and mirabegron. For OAB drug monotherapies, mirabegron had the highest persistence in both male and female cohorts.ConclusionsThis study provides a better understanding of the recent landscape of LUTS drug use in UK clinical practice. It highlights potential undertreatment of storage symptoms in men with LUTS and the low use of combination OAB treatments.

Impact of COVID-19 on Lung Allograft and Clinical Outcomes in Lung Transplant Recipients: A Case-control Study.

The impacts of COVID-19 on lung allograft function, rejection, secondary infection, and clinical outcomes in lung transplant recipients (LTRs) remain unknown. A 1:2 matched case-control study was performed to evaluate rehospitalization, lung allograft function, and secondary infections up to 90 d after COVID-19 diagnosis (or index dates for controls). Twenty-four LTRs with COVID-19 (cases) and 48 controls were identified. Cases and controls had similar baseline characteristics and lung allograft function. LTRs with COVID-19 had higher incidence of secondary bacterial infection (29.2% versus 6.3%, P = 0.008), readmission (29.2% versus 10.4%, P = 0.04), and for-cause bronchoscopy (33.3% versus 12.5%, P = 0.04) compared with controls. At d 90, mortality in cases versus controls was 8.3% versus 2.1% (P = 0.21), incidence of invasive fungal infections in cases versus controls was 20.8% versus 8.3% (P = 0.13) and forced expiratory volume in 1 s (FEV1) decline ≥10% from baseline occurred in 19% of cases versus 12.2% of controls (P = 0.46). No acute cellular rejection, acute antibody-mediated rejection, or new donor-specific anti-HLA antibodies were observed among cases or controls within 90 d post index date. We found LTRs with COVID-19 were at risk to develop secondary infections and rehospitalization post COVID-19, compared with controls. While we did not observe post viral acute cellular rejection or antibody-mediated rejection, further studies are needed to understand if LTRs with COVID-19 who did not recover baseline lung function within 90 d have developed chronic lung allograft dysfunction stage progression.

Burden of Pneumonia Among Hospitalized Patients with Influenza: Real-World Evidence from a US Managed Care Population

IntroductionPneumonia is among the most prevalent complications of influenza. The purpose of this study is to quantify the burden of pneumonia among hospitalized patients with influenza.MethodsReal-world retrospective data from 01JAN2014-30JUN2019 (study period) were obtained from Optum’s de-identified Clinformatics® Data Mart Database (2007–2020) for patients who had ≥ 1 diagnosis for influenza during the identification period and ≥ 1 all-cause inpatient visit within 1 day of diagnosis. Cases had ≥ 1 diagnosis claim for an influenza-related pneumonia within the 30 days after the initial influenza diagnosis date. Controls had no evidence of influenza-related pneumonia in the 30 days following the initial influenza diagnosis. Final 1:1 matching was determined using propensity score matching (PSM). Statistical significance between the cohorts was tested.ResultsAfter PSM, there were 4878 hospitalized patients with influenza in each of the case and control groups. During the index hospitalization, cases vs. controls had longer length of stay [Mean (standard deviation): 6.5 (8.3) vs. 1.9 (3.7)], greater intensive care unit (ICU) use (38.4 vs. 16.8%), and greater mechanical ventilation use (invasive: 11.4 vs. 2.3%; non-invasive: 6.8 vs. 2.6%) (all p < 0.001). Cases also had higher readmission rates than controls (12.3 vs. 3.5% within 30 days; 20.0 vs. 6.1% within 90 days; p < 0.001 for both). Post-index date direct all-cause healthcare costs were higher for cases than for controls (median total cost: $18,428 vs. $621 for 30 days; $21,774 vs. $3312 for 90 days; $25,960 vs. $8699 for 6 months; $35,875 vs. $21,619 for 1 year; all p < 0.001).ConclusionsPneumonia as a complication of influenza increases risk of mortality and leads to greater healthcare resource use and direct medical costs among patients hospitalized with influenza. These effects are seen early during the index hospitalization and within the first 30 days after diagnosis, but their impact continues throughout a year of follow-up.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00169-2.

Hemoglobin A1C testing frequency among patients with type 2 diabetes within a US payer system: a retrospective observational study

Objective The American Diabetes Association (ADA) guidelines recommend A1C testing schedules for patients with type 2 diabetes; however, level of real-world guideline adherence remains unclear. The current study evaluated A1C testing frequency and its association with glycemic control and cardiovascular outcomes. Methods A retrospective study was conducted utilizing Aetna’s Enterprise Data Warehouse. Adult patients with a medical claim for type 2 diabetes in 2017 (index date) were included. Patients had continuous enrollment through December 2019 and ≥1 reported A1C measurement from 2017 to 2019. Follow-up was up to 36 months post-index date. Results Of the 112,572 eligible patients, 50.0% were female and median age was 70 years; 32.9% of patients with controlled baseline A1C (<8%, 64 mmol/mol) received less than the 2 tests/year recommended by the ADA, while 60.6% of patients with uncontrolled baseline A1C received less than the quarterly testing recommended by the ADA. More frequent testing was associated with age (65–75 years), uncontrolled baseline A1C and presence of comorbidities. In separate multivariable models, 2–3 A1C tests/year were associated with greater likelihood of A1C < 8% (64 mmol/mol) vs. <2 tests/year (OR = 1.07, 95% confidence interval [CI] 1.02–1.12), while >3 tests/year was associated with a modestly increased risk of cardiovascular events vs. <2 tests/year (OR = 1.08, 95% CI 1.01–1.15). Conclusions A large proportion of type 2 diabetes patients were not tested per guideline recommendations. The relationship between A1C testing frequency and glycemic control was inconsistent, though there was a significant association between more frequent testing and experiencing a CV event.

Association of physician specialty with psoriatic arthritis treatment and costs.

To describe current psoriatic arthritis treatment and costs by provider specialty using real-world claims data. Observational, retrospective cohort study of patients in the IBM MarketScan Commercial and supplemental Medicare databases. Eligible patients had newly diagnosed psoriatic arthritis with 12 months of continuous enrollment pre- and post index date for their initial claim. Patients were assigned to 1 of 5 provider specialty cohorts. During the 1-year follow-up period, we collected psoriatic arthritis treatment agent and regimen type and total annual medical and health care costs. We used multivariate regression models to determine the conditional associations of provider specialty with costs. A total of 2132 patients with incident psoriatic arthritis qualified. Most providers were rheumatologists (n = 1365; 64%). Rheumatologists commonly prescribed oral small molecules (methotrexate, 56.3% of prescriptions; sulfasalazine, 8.6%; apremilast, 7.0%) as the index therapy, whereas 23.8% of prescriptions were for tumor necrosis factor inhibitors (adalimumab, 14.2%; etanercept, 7.9%; and infliximab, 1.7%). Compared with other specialists, dermatologists prescribed biologics and other specialty drugs more frequently-adalimumab (32.7%), apremilast (14.3%), etanercept (11.6%), and ustekinumab (8.8%)-and methotrexate less frequently (30.6%). The greatest unadjusted median health care costs were observed among dermatologists ($45,548) compared with rheumatologists ($30,411), primary care physicians ($29,927), rheumatologists/dermatologists ($27,393), and other specialists ($27,774). However, after adjusting for patient-level factors, multivariate regression analyses found that provider specialty was not associated with higher health care costs. In patients with newly diagnosed psoriatic arthritis, physician specialty was associated with different medication choices but not costs.

Clinical and Economic Burden of Transfusion-Dependent β-Thalassemia in Adult Patients in the United States

Introduction: β-thalassemia is a genetic blood disorder in which defective β-globin synthesis leads to ineffective erythropoiesis. Patients with transfusion-dependent β-thalassemia require lifelong management with blood transfusions and iron chelation therapy. Complications related to iron overload can cause significant morbidity and mortality, and it is well understood that the chronic management of this disease presents a substantial burden to patients in terms of healthcare visits and costs. However, the specific clinical and economic burden has not been well characterized in the USA.Objectives: The objectives of this study were to analyze the clinical and economic burden of current disease management for patients with transfusion-dependent (TD) β-thalassemia in the USA over a 1-year time period.Methods: This retrospective matched cohort study was conducted using the Truven Health MarketScan® Research Databases (Truven Health Analytics, Ann Arbor, MI). The MarketScan® Databases provide detailed utilization, outcomes, and cost data for healthcare services performed in inpatient and outpatient settings, and contains de-identified data from > 110 million patient lives. Adult patients with TD β-thalassemia and matched controls were identified between Jan 1, 2011 and Sep 30, 2015. Patients were required to be ≥ 18 years old at the index date with ≥ 12 months of continuous enrollment post index date. TD β-thalassemia patients were required to have ≥ 2 claims with a β-thalassemia (ICD-9-CM 282.44, ICD-10-CM D56.1) or hemoglobin E-β thalassemia (ICD-9-CM 282.47, ICD-10-CM D56.5) diagnosis, and ≥ 8 transfusion events to be defined as TD. Patients were excluded if they had ≥ 2 claims with any sickle cell diagnosis. Controls were required to have ≥ 1 medical claim and were excluded if they had a diagnosis of any thalassemia or sickle cell condition. Patients with TD β-thalassemia were matched to controls in a 1:5 ratio using exact matching based on age, sex, index year, payer type, and census division. Comorbidities were not used in matching because patients with TD β-thalassemia have a high burden of disease-associated comorbidities. Index date was the first claim for a β-thalassemia diagnosis in patients with TD β-thalassemia or the first medical claim for controls. Outcomes examined were disease burden such as comorbid conditions, healthcare utilization and costs specific to the management of TD β-thalassemia, as well as general healthcare utilization and costs during the 12 months post index date. Chi-squared tests and Fisher's exact test were used for categorical variables and the Wilcoxon-Mann-Whitney test was used for continuous outcomes.Results: Fifty patients with TD β-thalassemia met selection criteria and were matched to 250 controls. Mean age was 34.7 ± 9.1 years for both patients and controls. Patients with TD β-thalassemia had higher rates of diabetes (18% vs 6%, P = 0.009), cardiac disease (30% vs 2%, P < 0.001), hypogonadism (22% vs 7%, P = 0.002), osteoporosis (16% vs 1%, P < 0.001), and hypothyroidism (12% vs 4%, P = 0.045) compared with controls. On average, patients with TD β-thalassemia required 17 transfusions per year, 23 days apart. Mean number of outpatient visits was significantly higher in the TD β-thalassemia cohort compared with matched controls; however, inpatient and ER visits were not significantly different (Table 1). Mean total healthcare costs among the TD β-thalassemia cohort were USD 128,062 ± 62,260, compared with USD 5,438 ± 11,855 in controls (P < 0.001). Medical and medication costs were significantly higher in the TD β-thalassemia cohort compared with matched controls (Table 2). Among patients with TD β-thalassemia, total costs were primarily driven by chelation and transfusion costs, with other costs displayed in the figure. The majority of patients with TD β-thalassemia received oral chelators (72%), whereas 30% of patients received injectable chelators; 14% of patients received both oral and injectable chelators.Conclusions: Ongoing comprehensive treatment for TD β-thalassemia poses a substantial clinical and economic burden as compared with matched controls. Patients with TD β-thalassemia had significantly higher healthcare resource utilization, medication costs, and total costs compared with matched controls, and required frequent visits to their healthcare provider, which poses a burden to their quality of life and work productivity. [Display omitted] DisclosuresSheth:Novartis, Celgene, ApoPharma, Bluebird Bio: Consultancy. Weiss:Celgene: Employment; Zocdoc: Other: Equity ownership (options have not vested yet); Zocdoc: Other: Husband's employment. Parisi:Celgene: Employment, Equity Ownership. Ni:Celgene: Employment.

Real-World Patterns of Care for Patients with Follicular Lymphoma Treated with Lenalidomide and Rituximab (R2) in the US Medicare Population

Introduction: Follicular lymphoma (FL) is the most common indolent lymphoma and the second most common subtype of non-Hodgkin lymphoma (NHL). While rituximab-based immunochemotherapy remains a standard in front-line and relapsed FL settings, novel therapies hold the potential for chemotherapy-free treatment and may offer particular clinical benefit in the subgroup of patients with early relapse following immunochemotherapy. Rituximab with lenalidomide (R2) represents one such chemotherapy-free regimen currently in late-stage clinical trials for indolent lymphoma. While we await final reports from these ongoing trials, little is known about the current use of R2 in the routine care of patients with FL.M ethods: Our population-based cohort study utilized 100% Medicare claims data from January 2009 through December 2014. We selected a population of patients with FL (ICD-9: 202.0x) with at least one claim for rituximab during the identification period (January 1, 2010 through October 31, 2014). We then identified the subgroup of patients who received R2 by requiring claims for at least two consecutive cycles of lenalidomide and rituximab. The first prescription date for lenalidomide was defined as the index date. Patients were required to have continuous medical and pharmacy benefits for ≥ 12 months pre-index date (the baseline period), and ≥ 2 months post-index date (the follow-up period). Treatment discontinuation was defined as a gap in therapy of > 60 days. Patients initiating R2 within 90 days of a prior treatment were considered refractory to previous therapy. Patient demographics, clinical characteristics, and previous treatment regimens were recorded throughout the pre-index period. Patients receiving R2 were followed until the end of data availability.Results: Of 18,199 patients with FL receiving rituximab-based therapy during our study period, 226 (1.2%) were identified as receiving R2. The median age at the time of receiving R2 was 75 years (interquartile range [IQR] = 9 years); patients were mostly male (56.2%) and white (89.8%). Comorbid conditions at the initiation of R2 therapy were common, with a mean Charlson comorbidity index score of 5.1. Medical claims related to anemia (65.5%), chronic obstructive pulmonary disease (36.7%), and kidney dysfunction (30.5%) were the most prevalent comorbid conditions. The median time from the first identifiable FL claim until R2 initiation was 589 days (IQR = 895 days). Almost all patients (n = 224) showed evidence of previous FL-related treatment, with 39% showing evidence of at least two prior lines of treatment during the study period before initiating R2 therapy. A significant proportion of patients were refractory to their previous therapy (57.5%), and of those patients 35.3% were receiving R-chemotherapy, 26.2% were receiving rituximab monotherapy, and the remaining 38.5% were receiving other chemotherapy agent or regimens. The most frequent treatment regimens received in the pre-R2 period were rituximab monotherapy (42.5%), rituximab + bendamustine (38.9%), R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone [24.4%]), and rituximab + cyclophosphamide (20.4%). Additionally, 26.1% of patients had prior radiotherapy use. The median treatment gap between previous FL therapy and R2 was 124 days (IQR = 293 days). The median duration of R2 therapy was 100 days (IQR = 99 days).Conclusions: In our large US population-based study of older patients with FL receiving therapy between 2009 and 2014, R2 therapy was used infrequently compared with rituximab monotherapy and standard immunochemotherapy. R2 was nearly exclusively administered in the relapsed setting, with almost half of patients receiving R2 immediately being refractory to other rituximab-based treatments. With claims through the end of 2014, our study does not account for the impact of other recently approved novel FL therapies. Overall, R2 therapy has historically been limited to the relapsed/refractory FL setting and future observational studies will be important to assess whether upcoming R2 trial results impact FL treatment and outcomes in the real-world setting. DisclosuresHuntington:Pharmacyclics: Honoraria; Janssen: Consultancy; Celgene: Consultancy, Other: Travel. Keshishian:Celgene: Other: Employee of STATinMED Research, which is a paid consultant to Celgene Corporation. Xie:Celgene: Other: Employee of STATinMED Research, which is a paid consultant for Celgene Corporation. Baser:Celgene: Other: Employee of STATinMED Research, which is a paid consultant for Celgene Corporation. McGuire:Celgene: Employment, Equity Ownership.

Lenalidomide Maintenance for Patients with Newly Diagnosed Multiple Myeloma Post Autologous Stem Cell Transplant: A Comparison of Real-World Treatment Outcomes and Costs

BACKGROUNDIn 2017, lenalidomide maintenance therapy (R-MT) was approved for patients (pts) who received an up-front autologous hematopoietic stem cell transplantation (ASCT) in the United States (US) and Europe. The total cost of care for pts on R-MT in the US has not been previously studied using a large administrative claims database. This study aimed to compare real-world outcomes and costs among pts with newly diagnosed multiple myeloma (MM) receiving R-MT vs no maintenance (No-MT) post ASCT.METHODSFrom the Truven Marketscan data set, we identified adult pts with ≥ 2 claims for MM (International Classification of Diseases, 9th/10th Revision, Clinical Modification code: 203.0x, C90.0x) 30 days apart and ≥ 1 MM treatment during the identification period (1/1/2011 to 9/30/2016). Pts were required to have continuous enrollment for 6 months pre and ≥ 6 months post initial ASCT date plus 90 days (index date), in addition to ≥ 1 full cycle of therapy with a valid first-line regimen, and evidence of ASCT during follow-up period. Patients were excluded if they had evidence of prior MM diagnosis or treatment. R-MT was defined as lenalidomide monotherapy of < 20 mg per day for ≥ 21 of 28 days. Treatment outcomes and healthcare costs during follow-up were compared among those initiating R-MT vs No-MT. Time to treatment discontinuation (TTTD) was defined as the duration from initiation of R-MT to discontinuation of R-MT. Time to next treatment (TTNT) was defined as the duration from the index date until the initiation of another second-line therapy. Kaplan-Meier (KM) and Cox proportional hazard models were performed to evaluate TTTD and TTNT. Per patient per month (PPPM) total healthcare costs were calculated at 12, 24, and 36 months among pts initiating R-MT or No-MT. Pharmacy costs included oral MM treatments and other oral medications. Outpatient costs were composed of IV medications and physician and ER visits, while hospitalizations were part of inpatient costs. Generalized linear regression models with negative binomial distribution and log link function were used to assess differences in PPPM while adjusting for differences in baseline characteristics.RESULTSA total of 250 and 233 pts initiated R-MT and No-MT, respectively. Mean age (58.5 vs 58.0 y, P= .5236) and Charlson Comorbidity Index score (5.2 vs 5.3, P= .5234) were similar, but there were more males in the No-MT group (52.0% vs 61.4%, P= .0378). Time from start of first-line regimen to ASCT (5.48 vs 5.47 months, P= .9589) and the mean follow-up time post index date (22.1 vs 21 months, P= .1414) were similar in both groups. R-MT pts had a median duration of maintenance of 10 months. The median TTTD using the KM method was 21.02 months (95% CI: 16.78, 25.76). During the study period, a total of 60 (24%) and 99 (42.5%) R-MT and No-MT pts received a second-line treatment. At 12, 24, and 36 months, the proportion of pts who had a second-line treatment was as follows: R-MT-12.4%, 21.2%, 22.8%; No-MT-35.2%, 40.3%, 42.1%. Median TTNT was significantly longer among those treated with R-MT vs No-MT (Figure 1). Adjusted total PPPM costs during the first 12 months of follow-up was higher among pts treated with R-MT vs No-MT ($13,095 vs $8,910, adjusted difference $4,514, P < .0001). Mean pharmacy PPPM costs were higher in R-MT pts ($8,603 vs $2,269, P < .0001) while outpatient costs were higher in the No-MT group ($3,761 vs $5,360, P < .0001), and inpatient costs were similar ($731 vs $1,281, P < .5076). The adjusted difference in total PPPM costs during 12-24 months of follow-up was $6,579, P < .0001. A similar cost trend was observed in months 24-36 of follow-up; however, even fewer patients had sufficient follow-up: Adjusted difference: $6,110, P= .0024.CONCLUSIONPts remain on R-MT for several months to well over a year. R-MT pts incurred higher costs within the study period; however, their TTNT was significantly longer, and they were over half as likely to progress to a second-line treatment compared with No-MT pts. Pharmacy costs in R-MT pts were higher in the initial year of follow-up while No-MT pts had higher outpatient costs, presumably driven by the need for second-line therapy in a higher proportion of patients. Additional follow-up is required to assess total healthcare costs in subsequent years. [Display omitted] DisclosuresHari:Celgene: Consultancy, Honoraria, Research Funding. Ung:Celgene Corporation: Other: Fellowship is funded by Celgene. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Ni:Celgene: Employment. Parikh:Celgene Corporation: Employment. Agarwal:Celgene Corporation: Employment.

Measurement of Pharmacist-Physician Collaborative Care on Therapeutic Inertia in Patients With Type 2 Diabetes.

Team-based care practice models have been shown to improve diabetes-related therapeutic inertia, yet the method and type of antidiabetic treatment intensification (TI) leading to improvements in glycemic control are not well understood. To evaluate time to TI in a pharmacist-physician practice model (PPM) as compared with usual medical care (UMC), explore the method and type of antidiabetic TI, and evaluate achievement of hemoglobin A1C (A1C) goal among each cohort. This was a retrospective cohort study conducted between January 1, 2017, and December 31, 2018. Median time to TI was calculated and compared between patients in the PPM and UMC groups using the log rank test. Descriptive statistics were used to evaluate the method and type of TI and A1C goal achievement. A total of 56 patients were included. The median (interquartile range) time to antidiabetic TI among the PPM cohort was 37.5 days (8, 216.5), as compared with 142 days (16, 465) in the UMC cohort (P = 0.19). At 1 year post-index date, 25% of patients in the PPM cohort reached their A1C goal compared with 18.8% of patients in the UMC cohort. This effect was maintained in the subgroup (n = 49) of patients receiving TI (23.1% vs 17.8%). A shorter time to TI and improvement in A1C goal achievement was observed with pharmacist-physician care compared with UMC. These findings suggest that pharmacist-physician care may be one of several interventions necessary to overcome therapeutic inertia in diabetes care.

Real-World Claims Analyses of Comorbidity Burden, Treatment Pattern, Healthcare Resource Utilization, and Costs in Pediatric Psoriasis.

There are limited real-world data on treatment patterns, comorbidities, and healthcare burden in pediatric patients with psoriasis. We examined patient demographics, comorbidity burden, treatment patterns, and healthcare use and costs in pediatric psoriasis. A retrospective, real-world, exploratory study was conducted using US claims databases. Pediatric patients aged < 18years with newly diagnosed psoriasis (index date) were selected from IBM® MarketScan® databases (2016-2018). Patients were enrolled continuously for ≥ 12months pre- and post-index date. Pre-index demographics, comorbidity, treatment drug classes prescribed, and post-index healthcare resource utilization and costs were studied. Study measures are reported for total population and by severity (categorized as mild and moderate-to-severe psoriasis). Variables were compared using t-test (continuous) or chi-square and Fisher's exact test (categorical). Overall, 4754 pediatric patients with psoriasis (58.3% females) met the selection criteria and were included in the study. Mean and standard deviation (SD) age was 12.6 (3.7) years on index date, with 13.4% patients having moderate-to-severe psoriasis. The mean (SD) Deyo-Charlson Comorbidity Index was 0.14 (0.40); anxiety (6.6%), depression (4.1%), and obesity (3.9%) were the most prevalent comorbidities observed. Topical treatments were prescribed to most patients as first-line treatment of mild (79.1%) and moderate-to-severe (52.0%) psoriasis. Other first-line therapies prescribed in moderate-to-severe cases included non-biologic systemics (21.0%), phototherapy (15.0%), and biologics (9.2%). Healthcare use and costs increased with psoriasis severity during the post-index period. Mean annual total all-cause costs per patient were higher for patients with moderate-to-severe psoriasis compared with mild psoriasis ($27,541 vs. $5,034; P < 0.001). Psychiatric, metabolic, and inflammatory disorders were observed comorbidities in pediatric patients with psoriasis. For moderate-to-severe psoriasis, topicals, phototherapy, and biologics were a common first-, second-, and third-line treatment sequence. Higher unadjusted healthcare costs by severity were driven by outpatient prescription costs.

Treatment Patterns and Outcomes, Before and After Humulin R U-500 Initiation, Among High-Dose Type 2 Diabetes Mellitus Patients in the United States

ObjectiveSeverely insulin-resistant type 2 diabetes (T2D) patients face unique treatment challenges. Humulin R U-500 (U-500R) as insulin monotherapy with both basal/bolus properties addresses these challenges, although it remains understudied. This retrospective study compared real-world patient characteristics, treatment patterns, and outcomes before and after U-500R initiation. MethodsAdults with T2D on dispensed doses of >180 units/d U-500R monotherapy (index date=first fill) with ≥9-month continuous enrollment both pre- and post-index date and ≥180 units/d insulin pre-index were identified using Veterans Health Administration data (January 1, 2014-January 30, 2017). Overall group was further stratified into elderly and 201 to 300 units dispensed total daily dose (dTDD) subgroups. Syringe and KwikPen users were separately analyzed as subcohorts. Treatment patterns (dTDD), insulin dosage (units/kg), proportion of days covered (PDC) with insulins, and outcomes (HbA1c and hypoglycemic events) were descriptively evaluated, with regression models used to confirm associations between exposure and outcomes. ResultsAmong 951 U-500R initiators (overall group), mean dTDD (248.5 vs 392.1), percentage of patients with insulin dosage >2 units/kg (38.6% vs 88.1%), and mean PDC (73% vs 77%) significantly increased from the pre- to post-index periods (all P<.001). Changes in HbA1c (9.3% vs 8.5%; P<.0001) and hypoglycemia events per patient per year (2.1 vs 3.1, P<.0001) were statistically significant and confirmed by regression models (P<.0001). Subgroups (elderly, 492; 201 to 300 units, 148) and device subcohorts (syringe, 714; KwikPen, 244) showed similar trends. ConclusionU-500R initiation was associated with significantly improved treatment compliance patterns and glycemic control, with modest increase in hypoglycemia events.

Burden and cost of comorbidities in patients with neuromyelitis optica spectrum disorder

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is associated with various comorbidities, including non-autoimmune and autoimmune conditions. The burden and cost of illness for NMOSD are unclear, particularly in the context of comorbidities. MethodsClaims data from IBM MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018 were analyzed. Patients with NMOSD were specified as having inpatient or outpatient claims for NMOSD diagnosis or specific NMOSD symptoms claims and no subsequent claims for multiple sclerosis (MS) or use of MS disease-modifying therapy (DMT). Continuous enrollment ≥ 6 months before and ≥ 1 year after the first claim (index date) was required for study inclusion. Total costs stratified by comorbidities within 12 months post-index date were calculated per patient and compared 1:5 with matched non-NMOSD controls. ResultsA total of 162 patients with NMOSD and 810 non-NMOSD controls were evaluated. A significantly higher proportion of NMOSD patients had comorbidities than non-NMOSD controls (66.7% vs 41.5%; P < 0.001). Concomitant autoimmune disease occurred in 19.1% vs 4.9% (P < 0.001) of patients with NMOSD vs non-NMOSD controls. NMOSD patients incurred significantly higher total median (interquartile range) healthcare costs per patient ($68,386.48 [$23,373.54–$160,862.70]) than matched non-NMOSD controls with autoimmune disease ($17,215.13 [$6715.48–$31,441.93]; P < 0.001) or patients with NMOSD without autoimmune comorbidity ($23,905.42 [$8632.82–$67,251.54]; P = 0.022). Similarly, patients with NMOSD and non-autoimmune comorbidities incurred higher median healthcare costs than matched controls. ConclusionsPatients with NMOSD experience significant disease burden and cost that are amplified by comorbidities. Effective therapies are needed, particularly for patients with concomitant autoimmune disease.

649-P: Impact of Early Initiation of Dulaglutide on A1C in Patients with Type 2 Diabetes

This retrospective, observational study assessed glycemic control over a 6-month follow-up among patient cohorts with T2D who initiated dulaglutide (DU) 0.75 mg or 1.5 mg following use of either 1, 2 or 3+ oral antihyperglycemic drugs (OAD) during the 24-month pre-index period. This analysis used US claims data from the HealthCore Integrated Research Database (HIRD®) between November 2012 and February 2020 (index date=earliest DU fill between November 2014 and August 2019). Patients ≥18 years old with T2D, ≥1 pharmacy claim for OAD during the pre-index period, continuous enrollment from 24 months pre-index to 6 months post-index date, and ≥1 A1C result within both 6 months pre- and 6 months post-index were included. There were differences in patient characteristics between the cohorts with significant trends (*see figure) of increasing age, comorbidity index scores and pre-index A1C seen with increasing number of prior OADs. Early initiation of DU, proxied by initiation after 1 OAD, resulted in an A1C reduction of 1.39%, and reductions of 1.30% and 1.01% in the 2 OAD and 3+ OAD cohorts, respectively (figure). Greater A1C reductions were observed across subgroups with higher pre-index A1C in each OAD cohort. In this real-world study, a clinically relevant reduction in A1C was seen within 6 months across all cohorts defined by the timing of initiation of DU, with increasing trend of A1C reduction seen with fewer number of prior OADs.View largeDownload slideView largeDownload slide DisclosureM. Hoog: Employee; Self; Eli Lilly and Company, Lilly Diabetes, Stock/Shareholder; Self; Abbott, Eli Lilly and Company, PPD. J. L. Smith: Employee; Self; HealthCore, Other Relationship; Self; Eli Lilly and Company. M. Yu: Employee; Self; Lilly Diabetes, Employee; Spouse/Partner; LifeLabs, Stock/Shareholder; Self; Lilly Diabetes, Stock/Shareholder; Spouse/Partner; Lilly Diabetes. J. Peleshok: Employee; Self; Eli Lilly and Company. R. Mody: Employee; Self; Eli Lilly and Company. M. Grabner: Other Relationship; Self; Eli Lilly and Company.