Association Between Hematologic Response and Change in Health-Related Quality of Life Among Patients with Light-Chain (AL) Amyloidosis.

Purpose: The purpose of this secondary data analysis was to examine the association between hematologic response and health-related quality of life (HRQoL) among patients with light-chain (AL) amyloidosis. Patients and Methods: Data for this secondary analysis were collected through a non-interventional, longitudinal, online self-report survey of patients with AL amyloidosis. Patients completed an initial online survey, with follow-up surveys administered 1, 6, 12, 18, and 24 months after completion of the initial survey. The online survey included an assessment of patients' most recent self-reported hematologic response status. Eight domains and 2 summary components of HRQoL were evaluated with the SF-36v2® Health Survey. A series of logistic regression models were used to examine the association between self-reported hematologic response at 24 months (dichotomized as new or maintained complete hematologic response; less than a complete response) and change in HRQoL from baseline to 24 months (dichotomized as meaningful worsening; improvement or preservation). Results: For all measured domains of HRQoL except physical functioning, there was no statistically significant relationship between meaningful worsening in HRQoL and hematologic response status at 24 months. Patients without a complete hematologic response had an odds of experiencing meaningful worsening of HRQoL that was similar to that of patients with a complete hematologic response. Conclusion: Among patients with AL amyloidosis, change in HRQoL was generally not associated with hematologic response. Achieving a complete hematologic response does not necessarily mean that a patient will experience increased or stable HRQoL. When defining treatment success, it is important to recognize that clinical markers such as hematologic response may not fully encapsulate the patient experience.

Health-Related Quality of Life Instruments for Clinical Trials in AL Amyloidosis: Report from the Amyloidosis Forum HRQOL Working Group.

Systemic AL (light chain) amyloidosis is a rare protein misfolding disorder associated with plasma cell dyscrasia affecting various organs leading to organ dysfunction and failure. The Amyloidosis Forum is a public-private partnership between the Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research with the goal of accelerating the development of effective treatments for AL amyloidosis. In recognition of this goal, 6 individual working groups were formed to identify and/or provide recommendations related to various aspects of patient-relevant clinical trial endpoints. This review summarizes the methods, findings, and recommendations of the Health-Related Quality of Life (HRQOL) Working Group. The HRQOL Working Group sought to identify existing patient-reported outcome (PRO) assessments of HRQOL for use in clinical trials and practice deemed relevant across a broad spectrum of patients with AL amyloidosis. A systematic review of the AL amyloidosis literature identified 1) additional signs/symptoms not currently part of an existing conceptual model, and 2) relevant PRO instruments used to measure HRQOL. The Working Group mapped content from each identified instrument to areas of impact in the conceptual model to determine which instrument(s) provide coverage of relevant concepts. The SF-36v2® Health Survey (SF-36v2; QualityMetric Incorporated, LLC) and Patient-Reported Outcomes Measurement Information System-29 Profile (PROMIS-29; HealthMeasures) were identified as instruments relevant to patients with AL amyloidosis. Existing evidence of reliability and validity was evaluated with a recommendation for future work focused on estimating clinically meaningful within-patient change thresholds for these instruments. For sponsors, the context of use-including specific research objectives, trial population, and investigational product under study-should inherently drive selection of the appropriate PRO instrument and endpoint definitions to detect meaningful change and enable patient-focused drug development.

In-hospital mortality in amyloid light chain amyloidosis: analysis of the Premier Healthcare Database.

Aim: Describe the clinical and economic burden of hospitalizations for amyloid light chain (AL) amyloidosis. Materials & methods: This retrospective analysis used nationally representative hospital discharge data (2017-2020) to report discharge status, resource use and costs for hospitalizations among patients with AL amyloidosis. Results: Of 1341 patients identified, 92% were discharged alive and 8% experienced in-hospital death. Compared with the average US hospital stay during 2017-2019 (4.7 days, mean costs of $13,046 and mean charges of $54,496), hospital stays for AL amyloidosis were longer and costlier (9.7 days, $27,098.61, $111,233.91), especially in patients with in-hospital death (12.2 days, $44,966, $182,338.18). Conclusion: AL amyloidosis is associated with significant clinical and economic burden.

Diagnostic amyloid light chain amyloidosis hospitalizations associated with high acuity and cost: analysis of the Premier Healthcare Database.

Aim: Estimate the frequency and costs of diagnostic admissions among hospitalized patients with amyloid light chain (AL) amyloidosis. Materials & methods: This retrospective analysis used nationally representative hospital discharge data from 2017 to 2020 to report resource use and cost for hospitalizations during which AL amyloidosis was diagnosed. Results: Of 1341 admissions, 17.6% were diagnostic. Bone marrow (79.5%) and kidney (44.9%) biopsies were the most common qualifying biopsies. Diagnostic hospitalizations had longer length of stay (14.5 vs 8.4 days; p < 0.001) and higher cost ($40,052 [USD] vs $24,360; p < 0.001) than nondiagnostic ones. Conclusion: Diagnostic admissions are more likely to be urgent/emergent, require longer stays and have higher costs compared with hospitalizations in known AL amyloidosis patients. Improved diagnostic pathways toward early diagnosis are needed.

Work Outcomes Among Patients with Light Chain (AL) Amyloidosis: Findings from Three Patient Cohorts.

BACKGROUND: Light chain (AL) amyloidosis is a rare and progressive disease that affects myriad organs and systems. Patients with cardiac involvement have the highest risk of death. This report compiles findings across three cohorts of patients with AL amyloidosis to understand patterns of employment and work impacts. METHODS: Data came from three cohorts recruited through patient advocacy organizations in the US. Patients in Cohort 1 completed the SF-36v2® Health Survey (SF-36v2), the Work Productivity and Activity Impairments - Specific Health Problem (WPAI) questionnaire, and the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The relationship between work impacts (WPAI scores) and HRQoL (SF-36v2 scores) was investigated using multivariable logistic regression and summarized according to cardiac severity using New York Heart Association (NYHA) classes estimated from KCCQ-12 scores. Changes in employment, days of missed work, and long-term disability due to AL amyloidosis were summarized for patients diagnosed in the past 24 months and stratified by NYHA class (Cohort 2). Findings were contextualized using patient interviews (Cohort 3). RESULTS: Work-related impacts, especially reduced productivity, were common among patients with AL amyloidosis. WPAI scores were significantly related to HRQoL (p<0.05 for all models). Among patients with cardiac involvement, the greatest degree of work impacts was observed for those in NYHA class 3 or 4. Changes in employment, missed work, and long-term disability were common among newly diagnosed patients, especially among those in NYHA class 3 or 4. Patient interviews supported the survey findings; patients described absences, reduced productivity at work, and loss of employment due to the disease and its treatment. CONCLUSION: Patients with AL amyloidosis, particularly those with more advanced disease, experience impacts across a range of employment-related outcomes. These findings highlight the need for more effective treatments and interventions which may improve functioning and patient outcomes, while reducing indirect costs associated with the disease.

Content Validation of the ATTR Amyloidosis Patient Symptom Survey: Findings from Patient and Clinician Cognitive Debriefing Interviews.

PURPOSE: Amyloid transthyretin (ATTR) amyloidosis is a rare, progressive, and fatal disease. The ATTR Patient Symptom Survey (ATTR-PSS) was previously developed through literature review and concept elicitation input from clinicians and patients and revised after evaluation by a patient focus group. This study further evaluated the content validity of the ATTR-PSS through qualitative cognitive debriefing interviews with clinicians and patients. METHODS: Seven clinicians and 10 patients with ATTR amyloidosis were interviewed individually regarding their overall impressions, the clarity and appropriateness of the survey, relevance of concepts measured, and comprehensiveness and comprehensibility of items and response choice sets. RESULTS: Clinicians acknowledged the usefulness of the ATTR-PSS in research and clinical settings. They suggested minor modifications to the survey instructions, the addition of 3 symptoms, and the transfer of 10 conditions from the symptom list to 2 separate items. Patients found the ATTR-PSS to be easy to complete and relevant to their experiences. Their feedback resulted in modification to instruction text, edits to the description of 4 symptoms, removal of 1 symptom, and addition of 2 diagnoses. CONCLUSION: The findings support the content validity of the ATTR-PSS as an appropriate measure of symptom frequency, severity, and impact in patients with wild-type and hereditary ATTR amyloidosis.

Untangling the clinical and economic burden of hospitalization for cardiac amyloidosis in the United States.

PURPOSE: Cardiac dysfunction is common in amyloid light-chain (AL) amyloidosis, a rare disease caused by extracellular deposition of misfolded immunoglobulin light chains. This study aimed to examine economic/clinical disease burden in hospitalized cardiac amyloidosis patients. PATIENTS AND METHODS: Cardiac amyloidosis patients ≥18 years old hospitalized between 2014 and 2016 were identified in claims if they had ≥1 inpatient claim consistent with amyloidosis and evidence of cardiac dysfunction. Descriptive statistics were reported. RESULTS: 3239 cardiac amyloidosis patients [1795 (55.4%) with concurrent renal disease] were identified. Mean (SD) length of stay was 8.3 (11.1) days. 25.2% were admitted to the intensive care unit. Mean overall hospitalization costs were USD$20,584. In-hospital mortality was 9.0% overall. 16.8% were readmitted within 30 days, with 11.2% dying in-hospital and a mean readmission cost of USD$18,536. CONCLUSION: Hospitalization for cardiac amyloidosis is costly, with high rates of readmission and mortality. Opportunities exist to improve care.

Associations between Health-Related Quality of Life and Self-Reported Emergency Room Department Visits and Inpatient Hospitalizations: Insights from a Secondary Data Analysis of Patients with Light-Chain (AL) Amyloidosis.

INTRODUCTION: Light-chain (AL) amyloidosis is a rare, progressive, and typically fatal disease. Health-related quality of life (HRQoL) has been shown to be a significant prognostic factor associated with clinical outcomes such as survival and response to treatment. A better understanding of how patterns of HRQoL may be prospectively associated with costly healthcare resource utilization, such as emergency department (ED) visits and inpatient hospitalizations, is warranted. METHODS: A secondary data analysis of a non-interventional, longitudinal online study of patients with AL amyloidosis (n = 224) was conducted. Negative binomial regression models were used to examine whether initial HRQoL scores (as measured by the SF-36v2® Health Survey [SF-36v2], where higher scores reflect better HRQoL) and changes in HRQoL were associated with the number of ED visits and inpatient hospitalizations during a 12-month period. Incidence rate ratios were interpreted by 5-point decrements in initial HRQoL scores and minimally important changes in HRQoL change scores. RESULTS: There were significant inverse associations between initial SF-36v2 scores and subsequent rates of ED visits and inpatient hospitalizations across all domains and summary components (p < 0.05 for all). In contrast, changes in physical, but not mental, functioning were associated with rates of ED visits and inpatient hospitalizations during a 12-month period of observation. CONCLUSION: Scores from patient-reported HRQoL surveys may be helpful in identifying patients at risk of future ED visits and hospital admissions, and may serve as a proxy for disease severity. Such information can provide stakeholders with insight into the humanistic and societal cost associated with AL amyloidosis.

Mortality and healthcare costs in Medicare beneficiaries with AL amyloidosis.

AIMS: Examine mortality and healthcare costs in Medicare beneficiaries with newly diagnosed immunoglobulin light chain (AL) amyloidosis. PATIENTS & METHODS: Cases were identified in 2012-2015 Medicare 5% data with ≥1 inpatient/≥2 outpatient claims consistent with AL amyloidosis and ≥1 AL-specific treatment. Cases were matched 3:1 with disease-free controls. Descriptive statistics were reported. RESULTS: A total of 249 (33.3%) cases were matched to 747 (66.7%) controls. A total of 19.7% of cases died within 1 year of follow-up versus 5.5% of controls; 30.6 versus 11.8% died within 2 years (p < 0.001). Mean (SD) costs in 1-year of follow-up were significantly higher among cases versus controls ($71,040 [65,766] vs $13,722 [27,493]; p < 0.001). CONCLUSION: Mortality was nearly four-times higher, and costs nearly five-times higher in beneficiaries with AL amyloidosis versus controls.

Epidemiology of AL amyloidosis: a real-world study using US claims data.

Amyloid light-chain (AL) amyloidosis is a rare disease caused by extracellular deposition of misfolded immunoglobulin light chains. This study aimed to provide an up-to-date estimate of prevalence and incidence of AL amyloidosis in the United States. Using claims databases from years 2007 to 2015, adults ≥18 years old with AL amyloidosis were included if they had (1) at least 1 inpatient or 2 outpatient claims consistent with AL amyloidosis and (2) received 1 AL-specific treatment. Prevalence was calculated as the number of AL patients divided by the number of enrollees on June 30th of each calendar year. Incidence was calculated as the number of patients with AL who were disease-free and enrolled with a health plan for 1 year prior, divided by the number of enrollees with enrollment from July 1st of the previous year to June 30th of each calendar year. The prevalence of AL amyloidosis increased significantly between 2007 and 2015, from 15.5 cases per million in 2007 to 40.5 in 2015, an annual percentage change (APC) of 12% (P < .001). The incidence ranged from 9.7 to 14.0 cases per million person-years (APC, 3%; P = .114) with no statistically significant increase. There was an increase in AL amyloidosis prevalence over a 9-year period coupled with stable incidence rates. Although there is no diagnosis code specific to AL amyloidosis and no validated method for identifying this condition using claims data, extrapolating from our data, there are at least 12 000 adults in the United States living with AL amyloidosis, and the number seems likely to rise.

Healthcare resource utilization and costs in amyloid light-chain amyloidosis: a real-world study using US claims data.

AIM: To estimate healthcare utilization and costs in amyloid light-chain (AL) amyloidosis. PATIENTS & METHODS: AL amyloidosis patients were identified in 2007-2015 claims databases if they had ≥1 inpatient/≥2 outpatient claims consistent with AL amyloidosis and received ≥1 AL-specific treatment. Descriptive statistics were reported. RESULTS: 50.1% (n = 3670) were admitted ≥1 time during the year, 11.3% (n = 827) ≥3 times. From 2007 to 2015, bortezomib use increased from 4.6 to 25.3%; melphalan use decreased from 18.9 to 2.0%; costs increased from 92,866 to $114,030. Among incident patients with at least 2 years of follow-up, healthcare utilization and costs decreased from first to second year post-diagnosis. CONCLUSION: AL chemotherapy-based prescribing practices changed. Total annual healthcare costs increased over time among AL amyloidosis patients.

Treatment Tolerability in Patients with Immunoglobulin Light-Chain Amyloidosis.

BACKGROUND: Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare and often fatal disease for which there is currently no treatment approved by the US Food and Drug Administration or the European Medicines Agency. Treatment options, which are typically based on therapies for multiple myeloma and are used off-label, are associated with substantial adverse events (AEs). Because the severity of AEs is often determined by clinicians, evaluations of treatment tolerability may not fully consider patients' own experience with treatment. OBJECTIVES: To explore the prevalence of AEs and treatment tolerability problems as reported by patients who received therapies for AL amyloidosis, and to examine the effects of AEs on treatment continuation and on health-related quality of life (HRQOL). METHODS: Patients with AL amyloidosis were recruited for this noninterventional, longitudinal, online survey. The patients responded to survey items regarding demographics, disease characteristics, most recent AL amyloidosis treatment, and HRQOL. The study analyses are based on data collected during the 6-month follow-up survey and are restricted to patients who completed the baseline and 6-month surveys and received treatment for AL amyloidosis within 6 months before the follow-up survey. RESULTS: A total of 100 patients met the inclusion criteria and were included in the study. The patients self-reported having a variety of AEs, which ranged in severity. Overall, 69.4% of patients had problems tolerating their treatment in the past 6 months, of whom 22% discontinued at least 1 therapy. In addition, approximately 33% of patients reduced their AL amyloidosis treatment because of AEs. Most often reported AEs included fatigue (83%), shortness of breath (53%), nausea (52%), and diarrhea (51%). Overall, 50% of the patients reported that their treatment was moderately well-tolerated and 41% said it was very well-tolerated. Those whose treatment was not well-tolerated had significantly worse HRQOL than patients whose treatment was well-tolerated. CONCLUSIONS: Patient-reported experiences should be considered by clinicians when making treatment-related decisions. More research is needed to explore additional factors that may contribute to treatment discontinuation in patients with AL amyloidosis.

The Cost of Hematopoietic Stem-Cell Transplantation in the United States.

BACKGROUND: Hematopoietic stem-cell transplantation (HSCT) requires highly specialized, resource-intensive care. Myeloablative conditioning regimens used before HSCT generally require inpatient stays and are more intensive than other preparative regimens, and may therefore be more costly. OBJECTIVE: To estimate the costs associated with inpatient HSCT according to the type of the conditioning regimen used and other potential contributors to the overall cost of the procedure. METHOD: We used data from the Truven Health MarketScan insurance claims database to analyze healthcare costs for pediatric (age <18 years) and adult (age ≥18 years) patients who had autologous or allogeneic inpatient HSCT between January 1, 2010, and September 23, 2013. We developed an algorithm to determine whether conditioning regimens were myeloablative or nonmyeloablative/reduced intensity. RESULTS: We identified a sample of 1562 patients who had inpatient HSCT during the study period for whom the transplant type and the conditioning regimen were determinable: 398 patients had myeloablative allogeneic HSCT; 195 patients had nonmyeloablative/reduced-intensity allogeneic HSCT; and 969 patients had myeloablative autologous HSCT. The median total healthcare cost at 100 days was $289,283 for the myeloablative allogeneic regimen cohort compared with $253,467 for the nonmyeloablative/reduced-intensity allogeneic regimen cohort, and $140,792 for the myeloablative autologous regimen cohort. The mean hospital length of stay for the index (first claim of) HSCT was 35.6 days in the myeloablative allogeneic regimen cohort, 26.6 days in the nonmyeloablative/reduced-intensity allogeneic cohort, and 21.8 days in the myeloablative autologous regimen cohort. CONCLUSION: Allogeneic HSCT was more expensive than autologous HSCT, regardless of the regimen used. Myeloablative conditioning regimens led to higher overall costs than nonmyeloablative/reduced-intensity regimens in the allogeneic HSCT cohort, indicating a greater cost burden associated with inpatient services for higher-intensity preparative conditioning regimens. Pediatric patients had higher costs than adult patients. Future research should involve validating the algorithm for identifying conditioning regimens using clinical data.

Prescription opioid abuse: a literature review of the clinical and economic burden in the United States.

Between 2002 and 2007, the nonmedical use of prescription pain relievers grew from 11.0 million to 12.5 million people in the United States. Societal costs attributable to prescription opioid abuse were estimated at $55.7 billion in 2007. The purpose of this study was to comprehensively review the recent clinical and economic evaluations of prescription opioid abuse. A comprehensive literature search was conducted for studies published from 2002 to 2012. Articles were included if they were original research studies in English that reported the clinical and economic burden associated with prescription opioid abuse. A total of 23 studies (183 unique citations identified, 54 articles subjected to full text review) were included in this review and analysis. Findings from the review demonstrated that rates of opioid overdose-related deaths ranged from 5528 deaths in 2002 to 14,800 in 2008. Furthermore, overdose reportedly results in 830,652 years of potential life lost before age 65. Opioid abusers were generally more likely to utilize medical services, such as emergency department, physician outpatient visits, and inpatient hospital stays, relative to non-abusers. When compared to a matched control group (non-abusers), mean annual excess health care costs for opioid abusers with private insurance ranged from $14,054 to $20,546. Similarly, the mean annual excess health care costs for opioid abusers with Medicaid ranged from $5874 to $15,183. The issue of opioid abuse has significant clinical and economic consequences for patients, health care providers, commercial and government payers, and society as a whole.

Opioid utilization patterns among medicare patients with diabetic peripheral neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) affects a large percentage of patients with type 2 diabetes and is associated with moderate-to-severe pain. Patients with DPN bear a substantial economic burden as a result of increased overall healthcare utilization. The reported costs of treating DPN are nearly $11 billion, with elderly (aged ≥65 years) patients with type 2 diabetes accounting for 93.1% ($10.2 billion) of the total costs. OBJECTIVES: To describe the real-world utilization patterns of long-acting opioids (LAOs) and chronic short-acting opioids (SAOs) use in a sample of Medicare enrollees (aged ≥65 years) with painful DPN, and to identify potential areas for improvement in the management of elderly patients with painful DPN who are treated with opioids. METHODS: In this retrospective pharmacy claims analysis, the Chronic Opioid Medication Use Evaluation (MUE) software was used to import and analyze individual plan, retrospective pharmacy utilization claims data from the MarketScan claims databases. Patients aged ≥65 years who had painful DPN as identified by ≥2 International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for painful DPN (250.6X or 357.2) in at least 2 quarters in 2009, and who had ≥1 claims for LAO and/or chronic use of SAO (≥60 days of continuous therapy), were selected for analysis. Pharmacy claim data were extracted for 12 months, and various opioid utilization measures were reported. RESULTS: A total of 1448 unique Medicare patients with painful DPN were identified who had 11,740 claims for an LAO and/or chronic use of an SAO. Of the 1448 patients, 62% had chronic use of an SAO, and of these, 89% had no concurrent claim for LAO (minimum, 60-day overlap). The most frequently filled LAOs were fentanyl transdermal (38%), oxycodone controlled release (CR; 26%), and morphine CR/extended release (ER)/sustained release (SR; 20%). The daily average consumptions for fentanyl transdermal, oxycodone CR, and morphine CR/ER/SR were 0.3, 2.5, and 2.4, respectively. Among the study population, 15.2% of the patients filled an LAO or SAO prescription at ≥2 pharmacies. Furthermore, these elderly patients with painful DPN used greater doses of LAOs than what is recommended in the package insert, and 1.6% of patients used high doses of acetaminophen and 15.2% utilized multiple pharmacies to obtain their opioid prescriptions. Moreover, this population had prevalent concomitant use of opioids and prescribed gastrointestinal (GI) medications. CONCLUSION: Results from our retrospective pharmacy claims analysis demonstrated that elderly patients with painful DPN use doses of LAOs above those recommended in the package insert, with some patients using high doses of acetaminophen and utilizing multiple pharmacies to obtain their opioid prescriptions. In addition, this population had prevalent concomitant use of opioids and prescription GI medications. The use of software, such as the Opioid MUE, to monitor opioid drug utilization trends and examine other utilization measures can assist healthcare decision makers and payers in their utilization reviews to appropriately manage this population.