Geographic variation in disease burden among patients with severe persistent asthma in the United States.

BACKGROUND: In the United States, a few studies have evaluated geographic variation of severe asthma at the subnational level. OBJECTIVE: To assess state-level geographic variation in the prevalence and characteristics of severe persistent asthma in the United States. METHODS: Patients aged above or equal to 12 years with severe persistent asthma were identified using nationally representative data from IQVIA open-source Medical/Pharmacy Claims and PharMetrics Plus databases (January 2019-December 2020). The index date was defined as the patient's earliest qualifying date for a severe asthma diagnosis. Baseline characteristics were measured during the 12-month pre-index period. Outcomes including exacerbation occurrence, asthma control, and medication use were measured during the 12-month post-index period and compared across states using census-level projections. RESULTS: A total of 2,092,799 patients with asthma were identified; 496,750 (23.7%) met criteria for severe persistent asthma and all inclusion criteria. Mean age was 50.5 years; 68.4% were females. The prevalence of severe persistent asthma varied across states, ranging from 19.6% (New Mexico) to 31.9% (Alaska). Among patients with severe persistent asthma, 40.9% had more than or equal to 1 exacerbation, ranging from 34.2% (Vermont) to 45.6% (Louisiana); 21.1% had uncontrolled disease, ranging from 16.5% (Vermont) to 24.0% (Arizona). Among patients with exacerbations, 13.7% had exacerbation-related emergency department visits or hospitalizations, ranging from 7.0% (North Carolina) to 17.7% (Nevada). Among patients with severe uncontrolled asthma, 15.6% used biologics post-index, ranging from 2.2% (Hawaii) to 27.9% (Mississippi). CONCLUSION: There is significant variability in severe persistent asthma prevalence and disease burden across US states. Reasons for geographic variation may include differences in socioeconomic/environmental factors or asthma management.

Lipid-Lowering Therapy Utilization and Dosage Among Patients with Acute Coronary Syndrome Events: A Retrospective Cohort from 12 Community Hospitals.

Introduction: Clinical practice guidelines recommend initiating a high-intensity LLT and continued monitoring of low-density lipoprotein cholesterol (LDL-C) following acute coronary syndrome (ACS). We used real-world data to describe LLT utilization after discharge and 1-year adherence. The reduction in LDL-C was also evaluated. Methods: Data were extracted from electronic health records (EHRs) from 12 hospitals in a large community healthcare system in midwestern United States between 2013 and 2019. Data on eligible patients recently discharged with an ACS event were linked to pharmacy claims data to describe LLT fill rates and 1-year post-discharge adherence. Adherence was reported as the proportion of days covered ≥80%. Results: Of the 10,589 eligible patients, 49% filled a high-intensity statin at discharge and only 36% were adherent at 1 year. The mean (SD) age was 66.1±13.3, 39.3% were females, 58.8% were Caucasian, and 53.0% had Medicare. There was a clear trend for greater fill rates at discharge among patients with higher LDL-C values than those with lower values (p<0.01). Key predictors of high-intensity (versus medium-intensity) LLT use within 21 days after an ACS event included ACS type (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.52-0.67 for NSTEMI versus STEMI), age group (OR: 0.59; 95% CI: 0.48-0.72 for >75 years versus <65 years), and statin use before index ACS event (OR: 1.56; 95% CI: 1.23-1.88). Conclusion: This real-world study found that despite recommendations in clinical practice guidelines, high-intensity LLT fill rates at discharge and 1-year adherence to LLT remain suboptimal. Clinical characteristics, including ACS type and LDL-C values, were strong predictors of filling and adherence to guideline-recommended therapy. Age, sex, and race/ethnicity disparities were observed in discharge fill rates and 1-year adherence. These results highlight the need for continued efforts at the patient and provider levels to improve LLT adherence among ACS patients.

Real-world characteristics of patients with sickle cell disease who initiated crizanlizumab therapy.

OBJECTIVE: To provide real-word evidence of patients with SCD initiating crizanlizumab, their use of other SCD treatments, and crizanlizumab treatment patterns. METHODS: Using IQVIA's US-based, Longitudinal Patient-Centric Pharmacy and Medical Claims Databases patients with a diagnosis of SCD between November 1, 2018, and April 30, 2021, and ≥1 claim for crizanlizumab (date of first claim = index date) between November 1, 2019, and January 31, 2021 who were ≥16 years of age, and had ≥12 months of pre-index data were selected for analysis. Two cohorts were identified based on available follow-up time (3- and 6-month cohorts). Patient characteristics were reported along with pre- and post-index SCD treatments and crizanlizumab treatment patterns (e.g. total doses received, gap-days between doses, days on therapy, discontinuation, and restarts). RESULTS: 540 patients met the base inclusion criteria (345 in the 3-month cohort and 262 in the 6-month cohort. Most patients (64%) were female with a mean (SD) age of 35 (12) years overall. Concomitant hydroxyurea use was observed in 19-39% of patients, while concomitant L-glutamine use was observed for 4-8% of patients. 85% of 3-month cohort patients received at least two doses of crizanlizumab, while 66% of the 6-month cohort received at least 4 doses of crizanlizumab. The median number of gap days between doses was 1 or 2. CONCLUSIONS: 66% of patients who receive crizanlizumab receive at least 4 doses within 6-months. The low median number of gap days suggests high adherence.

Burden of chemotherapy in patients with relapsed/refractory acute myeloid leukemia in the United States: a retrospective claims database study.

BACKGROUND: Real-world estimates of relapsed or refractory (R/R) acute myeloid leukemia (AML) chemotherapy episode costs are scarce. We quantified chemotherapy episode-related costs and healthcare resource use (HRU) in R/R AML. RESEARCH DESIGN AND METHODS: This real-world, retrospective analysis of United States claims from IQVIA's PharMetrics® Plus database (October 2008-September 2019) identified adults with R/R AML and ≥1 chemotherapy episode. Chemotherapy episode (ie, low- [LIC] or high-intensity [HIC] chemotherapy) costs and HRU were determined using inpatient, outpatient, and pharmacy claims. RESULTS: Mean (SD) and median total all-cause healthcare costs per R/R AML chemotherapy episode were $230,799 ($300,770) and $129,117. Mean (SD) and median adjusted direct R/R AML chemotherapy episode costs were $116,384 ($151,425) and $63,298, with increases noted from the first to the second and subsequent episodes and with HIC. Hospitalizations were the major cost driver; 64.1% of patients had ≥1 hospitalization and 36% required an intensive care unit stay. CONCLUSIONS: R/R AML chemotherapy episode costs were high, with higher costs reported with HIC and increasing lines of chemotherapy. Hospitalizations were a main cost driver. Novel therapies with comparable or improved effectiveness and decreased need for hospitalizations versus chemotherapy may help alleviate the clinical and economic burden of R/R AML.

Real-World Efficacy and Tolerability of Brigatinib in Patients with Non-Small Cell Lung Cancer with Prior ALK-TKIs in the United States.

BACKGROUND: Real-world evidence for brigatinib, a next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) used in ALK-rearranged non-small cell lung cancer, is scarce. This retrospective study evaluated real-world brigatinib utilization in the US post other ALK-TKIs. MATERIALS AND METHODS: Adults with ≥1 brigatinib claim (index date) between 1 April 2017 and 30 September 2020 in the IQVIA longitudinal pharmacy claims database were followed until dose reduction, discontinuation, or end of follow-up. Patients had ≥12 months pre- and ≥1-month post-index observations. RESULTS: A total of 413 patients treated with brigatinib were analyzed. Over 80% received ≥1 prior ALK-TKI; alectinib and crizotinib were the most common (58.8% and 51.3% patients, respectively). The median follow-up was 8.4 months. The median time to treatment discontinuation (TTD) for brigatinib was 10.3 months (95% CI, 8.2-15.0), with 45% remaining on therapy at 12 months. The TTD was shortest (~8 months) in patients receiving both crizotinib and alectinib and longest in patients who received alectinib only prior to brigatinib (11.8 months). Adherence was high, with 92.7% of patients having a medication possession ratio of >80%. The mean dose compliance score was 1.0. Most patients reached the brigatinib dose of 180 mg/day (77%); 13.2% of patients had a dose reduction, with 89.3% and 84.6% continuing 180 mg/day therapy at 3 and 6 months, respectively. CONCLUSIONS: Brigatinib appears to be effective and well-tolerated in the real-world ALK+ NSCLC population in the US, showing benefit in patients after a next-generation ALK-TKI. Notably, dose reduction rates appeared markedly less than those seen in trials when most trial-related dose reductions were for asymptomatic laboratory abnormalities.

Real-World Effectiveness of Dupilumab in Atopic Dermatitis Patients: Analysis of an Electronic Medical Records Dataset.

INTRODUCTION: While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch. METHODS: From Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy). RESULTS: More than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p < 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p < 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p < 0.0001 compared with pre-index). CONCLUSIONS: Consistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point.

Previously unrecognized risk factors for severe hypoglycaemia requiring emergency medical care in insulin-treated type 2 diabetes: Results from a real-world nested case-control study.

AIM: Several risk factors for severe hypoglycaemia (SH) are associated with insulin-treated diabetes. This study explored potential risk factors in adults with insulin-treated type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In this case-control study, adults with T2DM initiating insulin were identified in the IQVIA PharMetrics® Plus database. The index date was the date of the first SH event (cases). Using incidence-density sampling, controls were selected from those who had been exposed 'at risk' of SH for the same amount of time as each case. After exact-matching on the well-established factors, previously unreported risk factors were evaluated through conditional logistic regression. RESULTS: In 3153 case-control pairs, pregnancy [odds ratios (OR) = 3.20, p = .0003], alcohol abuse (OR = 2.43, p < .0001), short-/rapid-acting insulin (OR = 2.22/1.47, p < .0001), cancer (OR = 1.87, p < .0001), dementia/Alzheimer's disease (OR = 1.73, p = .0175), peripheral vascular disease (OR = 1.59, p < .0001), antipsychotics (OR = 1.59; p = .0059), anxiolytics (OR = 1.51, p = .0012), paralysis/hemiplegia/paraplegia (OR = 1.51, p = .0416), hepatitis (OR = 1.50, p = .0303), congestive heart failure (OR = 1.47, p = .0002), adrenergic-corticosteroid combinations (OR = 1.45, p = .0165), ß-adrenoceptor agonists (OR = 1.40, p = .0225), opioids (OR = 1.38, p < .0001), corticosteroids (OR = 1.35, p = .0159), cardiac arrhythmia (OR = 1.29. p = .0065), smoking (OR = 1.28, p = .005), Charlson Comorbidity Index score 2 (OR = 1.28, p = .0026), 3 (OR = 1.41, p = .0016) or ≥4 (OR = 1.57, p = .0002), liver/gallbladder/pancreatic disease (OR = 1.26, p = .0182) and hypertension (OR = 1.19, p = .0164) were independently associated with SH. CONCLUSIONS: Although all people with insulin-treated diabetes are at risk of SH, these results have identified some previously unrecognized risk factors and sub-groups of insulin-treated adults with T2DM at greater risk. Scrutiny of current therapies and comorbidities are advised as well as additional glucose monitoring and education, when identifying and managing SH in vulnerable populations.

Factors influencing series completion rates of recombinant herpes zoster vaccine in the United States: A retrospective pharmacy and medical claims analysis.

BACKGROUND/OBJECTIVES: Vaccination against herpes zoster (HZ) is an effective strategy in protecting the population against consequences of varicella zoster virus reactivation. Optimal immunogenicity with recombinant zoster vaccine (RZV) relies on completion of the 2-dose series within 2-6 months from the first dose. The objectives of this study were to estimate RZV completion rates and adherence with the recommended administration schedule in the general United States population aged at least 50 years and to evaluate factors influencing completion rates. METHODS: Longitudinal, open-source pharmacy and medical claims databases were analyzed for adults aged at least 50 years with a first RZV prescription filled between October 2017 and September 2019. The data were linked to Experian Marketing Services Consumer View data to obtain information regarding race. Completion rates and adherence were calculated overall and stratified according to claim source, age class, sex, and payer type. Logistic regression models were built for each subpopulation of interest to identify factors correlating with completion rates. RESULTS: Overall, cumulative completion rates were 70.41% and 81.80% at 6 and 12 months, respectively. Median time to second dose was approximately 4 months (4.08-5.13 months) and adherence 67.62%. Completion rates were lower in the medical claims database compared with the pharmacy claims database (48.98% vs. 73.23% at 6 months). Regression models confirmed that pharmacy claim was an independent factor for higher completion rates, while African American race and Medicaid status were associated with lower completion rates. Most comorbidities, including chronic obstructive pulmonary disease and type 2 diabetes mellitus, were associated with lower completion rates. CONCLUSION: Pharmacists contribute substantially to the overall high RZV completion rates in the United States. However, completion rates can be improved, especially in people receiving their first RZV dose at a physician's office. Future strategies should aim at lowering barriers to completing vaccination series in African Americans, Medicaid beneficiaries, and people with comorbidities.

Real-World Satisfaction with Secukinumab in Clearing the Skin of Patients with Plaque Psoriasis through 24 Months of Follow-Up: Results from US Dermatology Electronic Medical Records.

INTRODUCTION: Information on the long-term treatment satisfaction with secukinumab for patients with plaque psoriasis in real-world settings is limited. The objective of this study was to describe real-world treatment satisfaction in patients with plaque psoriasis who initiated secukinumab using data from an electronic medical records-based dermatology database. METHODS: Patients aged ≥ 18 years with plaque psoriasis in Modernizing Medicine Data Services' affiliate's database who received secukinumab 3/1/2018-1/21/2020 were included. Satisfaction with the treatment's effectiveness in clearing the skin of psoriasis was evaluated using a 5-point Likert scale during the 12-month baseline period and at 6-, 12-, 18-, and 24-month postindex visits for the overall population and at 6-, 12-, and 18-month postindex visits for subgroups stratified by prior biologic and systemic therapy use. Additionally, satisfaction levels were assessed among patients who were unsatisfied with treatment at baseline. RESULTS: Overall, 82.3% agreed that secukinumab was effective in clearing their skin at 6 months, which was maintained through 12 (81.7%), 18 (83.3%), and 24 months (81.4%). Similar results were observed in biologic-experienced/naive and systemic-experienced/naive patients. Overall mean (SD) treatment satisfaction improved from 2.49 (1.36) at baseline to 1.77 (1.06) at 6 months, with similar improvements in satisfaction scores reported at each follow-up period up through 24 months. Of the patients who were not satisfied at baseline, 77.9% reported being satisfied with their treatment at 6 months, which continued through 12 (74.4%), 18 (82.8%), and 24 months (71.4%). Patients receiving secukinumab experienced meaningful changes in percent affected body surface area and Physician Global Assessment scores that were sustained through 24 months, regardless of prior treatment experience. CONCLUSIONS: These real-world findings highlight the high level of sustained satisfaction with secukinumab treatment for improving and maintaining skin clearance in patients with moderate-to-severe disease, regardless of prior treatment experience.

Clinical and economic burden of neovascular age-related macular degeneration by disease status: a US claims-based analysis.

BACKGROUND: New treatment alternatives have revolutionized the management of nAMD. However, there is limited evidence on the clinical and economic burden of nAMD in commercially insured US patients. OBJECTIVES: To examine the clinical and economic burden in patients with nAMD by disease status in the commercially insured US patient population and to identify drivers of nAMD-related costs. METHODS: Patients with at least 1 International Classification of Diseases, 10th Revision Clinical Modification (ICD-10-CM) diagnosis for nAMD were identified from the IQVIA PharMetrics Plus database between April 2016 and August 2017 (index period). Patients had continuous enrollment for at least 6 months before and at least 12 months after the index date. Eye-level disease status was reported, along with intravitreal anti-VEGF treatment patterns. Health care resource utilization (HRU) (all-cause and nAMD-related) and direct health care costs were estimated over the 12 month follow-up period. Outcomes associated with falls and fractures were also assessed. Multivariate analysis identified drivers of annual nAMD-related outpatient costs among patients with anti-VEGF therapy. Incident patients (defined as those without an nAMD diagnosis 6 months prior to the index date) with at least 18 months of continuous enrollment after the index date were identified for a subset analysis to evaluate documented changes in disease status. RESULTS: A total of 6,076 patients with nAMD were identified for the prevalent cohort; 60.1%, 17.2%, and 5.9% had active CNV, inactive CNV, and inactive scar disease stage at index, respectively. The nAMD-related outpatient visit costs were roughly 4 and roughly 7 times higher, respectively, for the active CNV group ($8,658 [SD = $11,612]) compared with the inactive CNV ($2,406 [SD = $5,510]) and inactive scar ($1,198 [SD = $3,035]) groups (P < 0.0001). About 10% of prevalent patients had a fall/fracture claim over 12 months of follow-up. A total of 3,623 prevalent patients (59.6%) were eligible for the anti-VEGF treatment patterns analysis (mean [SD] duration of therapy = 7.7 [4.5] months; mean [SD] number of injections = 6.0 [3.7]). Qualified incident cases comprised 17.8% (n = 1,081) of the prevalent cohort. Approximately 20% of incident eyes with active CNV at baseline transitioned to inactive CNV. A total of 427 incident patients (39.5%) qualified for anti-VEGF treatment patterns analysis (mean [SD] duration of therapy = 6.2 [4.7] months, mean [SD] number of injections = 5.2 [3.5]). Significant drivers of total nAMD-related costs were the initial anti-VEGF agent and anti-VEGF injection frequency (P < 0.0001) in both prevalent and incident cohorts. CONCLUSIONS: The clinical and economic burden of nAMD treatment is substantial to the US healthcare system, where economic burden is higher among those with active CNV. Appropriate treatment may increase the duration of inactive disease periods and preserve visual acuity while lowering costs. DISCLOSURES: This study was funded by Allergan, an AbbVie Company. Allergan employees were involved in the study design, interpretation of data, writing of the manuscript, and the decision to submit for publication. Keyloun and Campbell are employees of Allergan. Multani, McGuiness, and Chen are employees of IQVIA, which received funding from Allergan for conducting the analysis. Almony and Shah-Manek have nothing to disclose.

Probabilistic Linkage of Randomized Controlled Trial Data to Administrative Claims: A Case Study of Patients from Baricitinib Clinical Trials.

INTRODUCTION: The aim of this work is to assess the feasibility of probabilistically linking randomized controlled trial (RCT) data to claims data in a real-world setting to inform future rheumatoid arthritis (RA) research. METHODS: This retrospective cohort study utilized IQVIA's Patient Centric Medical Claims (Dx) Database, IQVIA's Longitudinal Prescription Claims (LRx) Database, and Lilly's baricitinib RCT data from a sample of patients that consented to the linkage of their de-identified insurance claims to their de-identified RCT data. Patients were initially matched on age, gender, and three-digit ZIP code of the provider and further matched according to a point scoring system using additional clinical variables. RESULTS: A total of 245 patients from 49 US clinical trial sites were eligible for the study and 78 (31.8%) of these patients consented to participate. Of the 78 consented patients, 69 (88%) were successfully matched on age, gender, and three-digit ZIP code of the provider. Of the 69 patients successfully matched on age, gender, and three-digit ZIP code of the provider, 44 (63.8%) had at least one sufficient match using the point scoring system. Of these 44, 23 (52.3%) patients matched at a ratio of one RCT patient to one Dx/LRx patient, 11 (25.0%) at a ratio of 1:2, 7 (15.9%) at a ratio of 1:3 and three (6.8%) at a ratio of 1:4 or greater. To further improve match ratios, a variable hierarchy was applied to the 18 RCT patients with 2-3 matches. Overall, 38 of the 78 (48.7%) consented RCT patients were successfully matched 1:1 to claims database patients. CONCLUSIONS: This probabilistic linkage methodology demonstrates the feasibility, at a moderate linkage rate, of linking patients from RCTs to real-world data, which can provide a means to assess additional information not usually collected within or following a clinical trial.

Early examination of real-world uptake and second-dose completion of recombinant zoster vaccine in the United States from October 2017 to September 2019.

Shingrix (Recombinant zoster vaccine, RZV) was approved in October 2017 in the United States (US) for the prevention of herpes zoster in adults aged 50 years and older. The vaccine is administered in two doses, with the second dose administration recommended between two and six months after the first dose. Examination of uptake and series completion is important to ensure appropriate use, especially at the time of vaccine introduction. This report provides demographic characteristics of patients receiving RZV between October 2017 and September 2019, first- and second-dose uptake, and a cumulative estimation of second-dose completion by month for US adults aged 50 years and older. Monthly uptake increased rapidly since October 2017; overall, 7,097,441 first doses of RZV were administered along with 4,277,636 second doses during the observed timeframe. Among people with an observed first-dose administration, 70% and 80% completed the two-dose series within six and 12 months post initial dose, respectively. This evidence suggests that RZV has rapidly been adopted by a large population in the US and most are following manufacturer or policy recommendations regarding series completion. Further analyses are needed to explore potential patient, provider, and policy-relevant characteristics associated with second-dose completion that could serve as targets for further improvement.

Clinical and Economic Burden of Glaucoma by Disease Severity: A United States Claims-Based Analysis.

PURPOSE: To provide updated estimates of the clinical and economic burden in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG) by disease severity in the United States and to estimate incremental costs associated with disease progression. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with 1 or more International Classification of Diseases, 10th Revision, Clinical Modification, diagnoses for OAG or OHT who are 40 years of age or older. METHODS: Patients were identified from IQVIA's PharMetrics Plus database during the index period (October 1, 2015, to August 31, 2017). Patients had continuous health plan enrollment for 12 months or more before and after the index date (first OAG or OHT diagnosis during index period) and were stratified by baseline disease severity based on diagnosis code. Annual eye-related outpatient healthcare use and costs were estimated on a per-user basis. A generalized linear model was used to estimate adjusted mean costs by severity and to evaluate the impact of observed disease worsening on costs. A multivariate logistic regression analysis evaluated the relationship between severity and odds of falls or fractures. MAIN OUTCOME MEASURES: Total eye-related outpatient costs and odds of falls or fractures. RESULTS: One hundred seventy-seven thousand three hundred fifty-two OHT and OAG patients were identified (67.8% with OAG). Open-angle glaucoma patients showed higher eye-related outpatient costs than OHT patients (median, $516 [interquartile range (IQR), $323-$898] vs. $344 [IQR, $197-$617], respectively). Patients with severe OAG showed higher eye-related outpatient costs than moderate and mild OAG patients (median, $639 [IQR, $381-$1264] vs. $546 [IQR, $345-$950] vs. $476 [IQR, $304-$765], respectively; P < 0.0001), as well as higher glaucoma-related pharmacy costs (median, $493 [IQR, $122-$1457] vs. $244 [IQR, $84-$1113] vs. $139 [IQR, $66-$818], respectively; P < 0.0001). In adjusted analyses, disease worsening was associated with at least 2-fold higher annual eye-related outpatient costs (P < 0.0001). Severe OAG patients had significantly higher odds of fall or fracture compared with OHT patients (odds ratio, 1.34; 95% confidence interval, 1.13-1.59). CONCLUSIONS: Updated estimates showed highest eye-related costs for those with severe disease and disease progression among patients with OAG and OHT. Severe OAG was associated with increased risk of falls or fractures compared with patients with OHT. Therapies that delay disease progression may provide clinical and economic benefits.

Economic and Clinical Burden Associated With Intensification of Glaucoma Topical Therapy: A US Claims-based Analysis.

PRECIS: Incremental addition of intraocular pressure-lowering topical drops is associated with shorter-lasting benefit and higher health-related costs with each additional agent, suggesting a need for new treatment options to improve disease control and reduce treatment burden. PURPOSE: The purpose of this study was to evaluate treatment intensification as a driver of clinical and economic burden in patients receiving topical glaucoma medications for open-angle glaucoma/ocular hypertension. METHODS: This retrospective analysis of administrative claims data (January 2011 to July 2017) from the IQVIA PharMetrics Plus database included diagnosed patients who initiated or intensified treatment with 1 to 4 topical glaucoma medications of a different drug class between January 2012 and July 2015 (index date being the first such event during this period). Patients with prior open-angle glaucoma surgery or an equal or greater number of topical glaucoma medication classes during the preindex period were excluded. Treatment intensification rates and eye-related outpatient costs were assessed over 24 months postindex. RESULTS: Of 48,402 patients (mean age: 61.4 y), 22,874 (47.3%), 16,214 (33.5%), 7137 (14.7%), and 2177 (4.5%) received a first, second, third, or fourth medication class, respectively, as their first observed initial or intensified regimen. Among cohorts receiving 1, 2, 3, or 4 medication classes, 7.8%, 12.2%, 17.2%, and 22.6% of patients and 12.6%, 18.5%, 25.9%, and 33.7% of patients had subsequent treatment augmentation (class addition or glaucoma procedure, laser or surgical) within 12 and 24 months postindex, respectively. Eye-related outpatient costs over 24 months increased with each additional topical glaucoma medication class at index [mean (SD): $1610 ($3460), $2418 ($4863), $2872 ($5110), and $3751 ($6608) in the 1, 2, 3, or 4 class cohorts, respectively]. CONCLUSION: Multiple-drop therapies yielded shorter-lasting benefits with each additional agent and were associated with the increased clinical and economic burden.

Economic burden and risk factors of migraine disease progression in the US: a retrospective analysis of a commercial payer database.

AIMS: To evaluate the prevalence and risk factors of migraine progression and to assess the incremental burden of migraine progression on healthcare systems. MATERIALS AND METHODS: Adult patients were required to have a migraine diagnosis in IQVIA's US adjudicated claims database between 1 January 2012 and 30 June 2016, continuous enrollment ≥12 months before and after the index date (i.e. the first observed migraine diagnosis), and ≥1 additional migraine diagnosis claim during the 12-month post-index period. A previously-developed algorithm identified patients with prevention-eligible episodic migraine (EM). All-cause healthcare resource utilization (HCRU) and costs were evaluated at baseline, over the follow-up period and pre/post progression from prevention-eligible EM to chronic migraine. Cox proportional hazards models were used to evaluate risk factors associated with progression. RESULTS, LIMITATIONS, AND CONCLUSIONS: Of the 125,436 patients with prevention-eligible EM that were initially identified, 5,790 (4.6%) were further identified as progressed. Patients who progressed had higher healthcare costs and higher medication use at baseline compared to patients that did not progress. Mean (SD) all-cause total costs per patient per month were $1,790 ($3,788), significantly higher in the post-progression period compared to $1,414 ($2,456) in the pre-progression period in patients who progressed (p < .0001). Younger age, female sex, initial diagnosis by a neurologist, chronic pain, and use of triptans and/or non-specific acute medications were all significant progression risk factors. Results are limited by the use of a heterogeneous population (incident, prevalent, treated, and untreated patients), coding biases, and lack of information on non-prescription drug utilization and plan limits. Limitations aside, there are substantial HCRU and cost burden associated with migraine progression. Younger age, female sex, and the use of specific drug classes are likely to increase migraine disease progression risk.

Economic and Clinical Burden of Acute Myeloid Leukemia Episodes of Care in the United States: A Retrospective Analysis of a Commercial Payer Database.

BACKGROUND: In the United States, the incidence of acute myeloid leukemia (AML) has steadily increased over the last decade; in 2019, it was estimated that AML would affect 21,450 new patients and lead to 10,920 deaths. Detailed real-world cost estimates and comparisons of key AML treatment episodes, such as in high-intensity chemotherapy (HIC), low-intensity chemotherapy (LIC), hematopoietic stem cell transplantation (HSCT), and relapsed/refractory (R/R), are scarce in the commercially insured U.S. OBJECTIVE: To examine health resource utilization (HRU), clinical burden, and direct health care costs across various AML treatment episodes in a large sample of commercially insured U.S. METHODS: A retrospective cohort analysis was conducted. Patients with newly diagnosed AML were followed to identify the key active treatment episodes across the course of their disease. Data were obtained from 2 sources: IQVIA's Real-World Data (RWD) Adjudicated Claims Database - U.S. (formerly known as PharMetrics Plus), which comprises adjudicated claims for more than 150 million unique enrollees across the United States, and IQVIA Charge Detail Master Hospital Database, which has detailed data regarding services received in an inpatient setting. Calculation of all-cause HRU was based on physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Calculation of all-cause health care costs was based on total allowed costs and reported by the following cost components: physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Symptom and toxicity events were estimated via proxies such as diagnosis codes, procedures, and treatments administered. RESULTS: The final study sample consisted of 1,542 HIC-induction (HIC-I), 591 HIC-consolidation (HIC-C), 628 LIC, 1,000 patients with HSCT, and 707 patients with R/R AML. Total mean episode costs were highest in R/R episodes ($439,104), followed by HSCT ($329,621), HIC-I ($198,657), HIC-C ($73,428), and LIC ($53,081) episodes. Across all treatment episodes, hospitalization was the largest contributor to cost with mean hospitalization costs ranging from $308,978 in the R/R setting to $49,580 for patients receiving LIC; of these, costs related to intensive care unit admission were a noteworthy contributor. In patients with R/R AML and HSCT, expenditures related to pharmacy utilization averaged $24,640 and $12,203, respectively, and expenditures related to physician office visits averaged $10,926 and $6,090, respectively; these expenditures were much lower across other episodes. Across all categories of symptom and toxicity events, cardiovascular events was the only category of event that was a significant predictor of higher cost across all episodes. Symptom and toxicity events commonly associated with AML were associated with significantly increased costs, especially in R/R episodes. CONCLUSIONS: This resource utilization and direct health care cost analysis highlights the substantial economic burden associated with key AML treatment episodes in the United States, specifically during HIC-I, HSCT, and R/R episodes. DISCLOSURES: This study was funded by Astellas Pharma. Astellas employees were involved in the study design, interpretation of data, writing of the manuscript, and the decision to submit the manuscript for publication. Pandya and Wilson are employees of Astellas Pharma U.S. Walsh was an employee of Astellas Pharma U.S. while the study was conducted. Chen, McGuiness, and Wade are employees of IQVIA, which received funding from Astellas Pharma U.S. Madeiros was employed at Stanford University while this study was conducted and received a consulting fee from Astellas for work on this study. Data discussed in this study were previously presented at the 59th Annual American Society for Hematology Meeting & Exposition, 2017; December 9-12, 2017; Atlanta, GA.

Economic and Clinical Burden of Relapsed and/or Refractory Active Treatment Episodes in Patients with Acute Myeloid Leukemia (AML) in the USA: A Retrospective Analysis of a Commercial Payer Database.

This retrospective study estimated healthcare resource use (HRU), symptoms and toxicities (SxTox), and costs in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML), stratified by hematopoietic stem cell transplantation (HSCT) status. Claims data were used to identify adult patients with AML diagnoses from 1 January 2008 to 31 March 2016 in the USA. Patients were considered R/R if they had an AML relapse ICD-9 code (205.02) or a line of therapy consistent with R/R disease. The final R/R sample (N = 707) included 476 patients with and 231 patients without HSCT. The mean total episode cost (from relapse date to death or end of study period) for all patients was $439,104 (with HSCT $524,595 and without HSCT $263,310). Inpatient visits accounted for the greatest cost component (mean $308,978) followed by intensive care unit stays (mean $221,537), non-clinician (e.g., lab tests) visits (mean $30,909), and outpatient pharmacy utilization (mean $24,640). Patients with HSCT appeared to have longer episodes of care compared with patients without HSCT (16.8 vs 11.1 months), perhaps reflecting longer survival for HSCT patients. Mean number of visits within each category and their associated costs appeared to be higher in patients with HSCT compared with patients without HSCT. Patients with HSCT appeared to experience more SxTox compared with patients without HSCT across all categories. Results of the current study suggest that there is a substantial HRU and cost burden on R/R AML patients in the USA receiving active treatments. More effective therapies with improved tolerability would meet this tremendous unmet need in the R/R AML population.Funding: Astellas Pharma, Inc.

Real-World Treatment Patterns, Time to Next Treatment, and Economic Outcomes in Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide or Carfilzomib.

BACKGROUND: Negligible real-world evidence exists for later line treatment of multiple myeloma (MM) to assist treatment decisions or reimbursement models, such as episode-based payments. OBJECTIVE: To describe the treatment patterns and clinical/economic outcomes when pomalidomide or carfilzomib is used for relapsed/refractory MM. METHODS: A U.S. claims database was used to identify MM patients with an initial pomalidomide or carfilzomib claim (index date) between February 1, 2013, and February 28, 2015, which was assumed to be relapse therapy. Treatment regimens were defined as all MM chemotherapy observed within 60 days of index. Patients receiving pomalidomide and carfilzomib within 60 days of index were excluded. Time to next treatment (TTNT), a progression proxy, was defined as the addition of a new agent > 60 days from index or as treatment restart following a > 90-day therapy gap. Cost estimations used plan-allowed amounts. Descriptive statistics were used to compare outcomes between treatment groups, and regression models were used to adjust for baseline patient characteristics. RESULTS: There were 454 patients initiating treatment with pomalidomide (n = 264) or carfilzomib (n = 190) during the index period. The most frequent initial regimens for pomalidomide patients included pomalidomide + dexamethasone (47.0%) and pomalidomide alone (33.0%); the most frequent regimens for carfilzomib patients were carfilzomib alone (45.3%) and carfilzomib + dexamethasone (14.7%). The most frequent next line treatment for pomalidomide patients who progressed was the addition of (14.0%) or switch to (15.0%) carfilzomib ± dexamethasone and for carfilzomib patients, the most frequent next line treatment was pomalidomide + dexamethasone (9.3%) and carfilzomib alone or carfilzomib + dexamethasone + cyclophosphamide (6.7% each). The median (95% CI) TTNT for pomalidomide patients was 11.9 (10.7-14.8) compared with 9.4 (7.7-10.0) months for carfilzomib (P = 0.060). For patients followed to progression (pomalidomide: n = 100, 37.9%; carfilzomib: n = 75, 39.5%), mean TTNT was longer for patients initiating therapy with pomalidomide (6.9 months) versus carfilzomib (5.3 months, P = 0.016). When adjusted for baseline confounders, pomalidomide patients had a nonsignificant longer time to a subsequent treatment line. Inpatient encounters observed during the index line were very low (mean = 1) for both groups; outpatient encounters were fewer in pomalidomide patients. Adjusted analyses revealed inpatient encounters were higher (P = 0.005), while outpatient use was lower in pomalidomide patients (P = 0.006). Unadjusted median costs incurred during the initial line were similar between the 2 groups (pomalidomide: $102,805; carfilzomib: $127,203; P = 0.110) but significantly lower in pomalidomide patients after adjusting for baseline characteristics (P = 0.013). Unadjusted per patient per month (PPPM) costs incurred over the entire follow-up period were lower in pomalidomide-initiated patients ($18,298 vs. $24,734, P = 0.001) but not statistically significant in adjusted analyses (P = 0.230). CONCLUSIONS: A longer time to a subsequent line of therapy was observed in pomalidomide patients compared with carfilzomib patients, although the difference lost significance in adjusted analyses. Compared with carfilzomib, pomalidomide patients were observed to have lower unadjusted median PPPM costs over the entire post-index period and lower adjusted mean monthly costs during initial therapy. DISCLOSURES: Funding for this study was provided by Celgene. Chen, McGuiness, and Wade are employees of QuintilesIMS, which was contracted by Celgene to undertake this research. McGuiness also owns stock in Pfizer. Parikh, Abouzaid, Purnomo, and Hussein are employees of Celgene and participated fully in the development and approval of the manuscript. Portions of the results of this research were previously presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; June 3-7, 2016; Chicago, Illinois. Study concept and design were contributed by Chen, Parikh, Abouzaid, McGuiness, and Wade. Chen and McGuiness took the lead in data collection, along with Wade, and data interpretation was performed by Hussein and Wade, with assistance from the other authors. The manuscript was written by McGuiness, Chen, and Wade, with assistance from Parikh and Abouzaid, and revised by McGuiness and Hussein, along with the other authors.