Real-world treatment patterns in patients initiating third-line therapy for relapsed or refractory multiple myeloma in Germany, Italy, the United Kingdom, France, and Spain.

OBJECTIVES: To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe. METHODS: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. RESULTS: Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). CONCLUSIONS: From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.

Treatment preferences of patients with relapsed or refractory multiple myeloma in the United States, United Kingdom, Italy, Germany, France, and Spain: results from a discrete choice experiment.

Introduction: Newer treatment options for relapsed/refractory multiple myeloma (RRMM) with efficacy and safety profiles that differ from traditional therapies have facilitated personalized management strategies to optimize patient outcomes. In the context of such personalized management, understanding how treatment characteristics influence patients' preferences is essential. This study assessed patients' preferences for RRMM treatment attributes and determined trade-offs between potential benefits, administration procedures, and adverse effects. Methods: Patients' preferences were evaluated using a discrete choice experiment (DCE). Patients with RRMM who reported failing two lines of anti-myeloma treatment (immunomodulatory agent and a proteasome inhibitor [PI]) or ≥ 3 lines (including ≥1 PI, immunomodulatory agent, or anti-CD38 monoclonal antibody), were recruited across the US, UK, Italy, Germany, France, and Spain. DCE attributes and levels were identified using a targeted literature review, a review of clinical data for relevant RRMM treatments, qualitative patient interviews, and input from clinical and myeloma patient experts. The DCE was administered within an online survey from February-June 2022. Preference data were analyzed using an error-component logit model and willingness to make trade-offs for potential benefits, and relative attribute importance scores were calculated. Results: Overall, 296 patients from the US (n = 100), UK (n = 49), Italy (n = 45), Germany (n = 43), France (n = 39), and Spain (n = 20) participated in the DCE. Mean (standard deviation) age was 63.8 (8.0) years, 84% had a caregiver, and patients had a median of 3 (range: 2-8) prior lines of therapy. Efficacy attributes most influenced patients' preferences, with increasing overall response rate (25-85%) and overall survival (6 months to 2 years) contributing to ~50% of treatment decision-making. Administration procedures were also considered important to patients. Avoiding individual side effects was considered relatively less important, with patients willing to tolerate increases in side effects for gains in efficacy. Patient characteristics such as rate of disease progression, sociodemographics, or clinical characteristics also influenced treatment preferences. Conclusion: Patients with RRMM were willing to tolerate increased risk of side effects for higher efficacy. Preferences and risk tolerance varied between patients, with preference patterns differing by certain patient characteristics. This highlights the importance of shared decision-making for optimal treatment selection and patient outcomes.

Care patterns of patients with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype.

BACKGROUND: Interstitial lung diseases (ILDs) include a variety of parenchymal lung diseases. The most common types of ILDs are idiopathic pulmonary fibrosis (IPF), autoimmune ILDs and hypersensitivity pneumonitis (HP). There is limited real world data on care patterns of patients with chronic fibrosing ILDs with a progressive phenotype other than IPF. Therefore, the aim of this study is to describe care patterns in these patients. METHODS: This retrospective cohort study used claims data from 2015 to 2019 from the Optum Research Database. The study population included adults (≥ 18 years old) with at least two diagnosis codes for fibrosing ILD during the identification period (1OCT2016 to 31DEC2018). A claim-based algorithm for disease progression was used to identify patients likely to have a progressive fibrotic phenotype using progression proxies during the identification period. Index date was the first day of progression proxy identification after fibrosing ILD diagnosis. Patients were required to have continuous enrollment for 12 months before (baseline) and after (follow-up) index date. Patients with an IPF diagnosis were excluded. Descriptive statistics were used to describe the patient population and care patterns. RESULTS: 11,204 patients were included in the study. Mean age of the patient population was 72.7 years, and 54.5% were female. Unclassified ILDs (48.0%), HP (25.2%) and autoimmune ILDs (16.0%) were the most common ILD types. Other respiratory conditions were prevalent among patients including chronic obstructive pulmonary disease (COPD) (58.9%), obstructive sleep apnea (OSA) (25.0%) and pulmonary hypertension (9.8%). During baseline, 65.3% of all patients had at least one pulmonology visit, this proportion was higher during follow-up, at 70.6%. Baseline and follow-up use for HRCT were 39.9% and 48.8%, and for pulmonary function tests were 43.7% and 48.5% respectively. Use of adrenal corticosteroids was higher during follow-up than during baseline (62.5% vs. 58.0%). Anti-inflammatory and immunosuppressive medication classes were filled by a higher percentage of patients during follow-up than during baseline. CONCLUSIONS: Comprehensive testing is essential for diagnosis of a progressive phenotype condition, but diagnostic tests were underutilized. Patients with this condition frequently were prescribed anti-inflammatory and immunosuppressive medications.

Characteristics of hospitalizations and emergency department visits due to generalized pustular psoriasis in the United States.

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare and severe, inflammatory skin disease. GPP is characterized by recurrent flares that consist of disseminated erythematous skin rash with sterile neutrophil-filled pustules that can result in an emergency department (ED) visit or hospital stay due to systemic complications. This study characterizes hospitalizations, ED visits, and inpatient treatment due to GPP in the United States (US). METHODS: A descriptive, retrospective cross-sectional analysis was conducted in Cerner Health Facts, a US electronic medical record database. Hospitalizations and ED visits were identified between 1 October 2015 and 1 July 2017. Visits were included in the study if they were GPP-related, defined as a GPP diagnosis (ICD-10-CM code: L40.1) in the first or second position at admission or discharge, and if the discharge date was within the study period. Hospitalizations and ED visits were the units of analysis. Demographics, comorbidities, medication use, and outcomes were characterized with descriptive statistics. Outcomes included length of stay, intensive care unit (ICU) admission, and death. RESULTS: A total of 71 GPP-related hospitalizations and 64 GPP-related ED visits were included in the study. Other specified inflammatory skin conditions (OSICS)/skin and subcutaneous tissue infections (54%/34%), fluid and electrolyte disorders (46%), hypertension (30%), septicemia (24%), and acute renal failure (18%) were the most frequently coded conditions accompanying a GPP-related hospitalization. OSICS/skin and subcutaneous tissue infections (47%/42%) were the most commonly coded conditions accompanying a GPP-related ED visit. Medication use during GPP-related hospitalizations included topicals (triamcinolone (42%); clobetasol (17%)), systemic corticosteroids (prednisone (20%); methylprednisolone (11%)), and non-biologic and biologic immunosuppressants (cyclosporine (6%); methotrexate (4%); etanercept (1%)). Analgesics (acetaminophen 67%; morphine 24%), and antibiotics (vancomycin 21%) were also common. The median length of stay for hospitalizations was 5 days. Three hospitalizations included an ICU admission and two hospitalizations resulted in death. CONCLUSIONS: The presence of concurrent immune-mediated conditions, and frequent prescribing of analgesics, including opioids, illustrate the burden of GPP in patients requiring acute and inpatient care.

Economic burden of generalized pustular psoriasis and palmoplantar pustulosis in the United States.

OBJECTIVE: To estimate healthcare resource utilization (HCRU) and economic burden of generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) in a commercially insured population the United States (US). METHODS: Adult patients with a GPP or PPP diagnosis were identified between April 1, 2016 and August 1, 2019 in the IQVIA PharMetrics Plus database. Patients required continuous enrollment in medical and pharmacy benefits 6 months before and ≥2 months after the index diagnosis. GPP and PPP cohorts were exactly matched 1:3 on demographics and index date to a plaque psoriasis and a control cohort of the general population. All-cause HCRU and cost measures (direct medical and pharmacy) were reported as per patient per month (PPPM). Generalized linear models estimated adjusted cost ratios between matched cohorts, controlling for comorbidities. RESULTS: HCRU was high among GPP and PPP patients. Rates of inpatient visits were 4 times higher in GPP patients and 2 times higher in PPP patients compared to their matched cohorts. GPP patients experienced significantly higher total healthcare costs compared to matched cohorts (GPP vs plaque psoriasis: cost ratio 1.36, 95% confidence interval (1.22, 1.50); GPP vs control: 5.58 (3.73, 8.36)). PPP patients had significantly higher total healthcare costs compared to the general population (4.11 (3.31, 5.11)), while costs were comparable to plaque psoriasis patients (1.06 (0.97, 1.16)). CONCLUSIONS: GPP and PPP patients have significant economic burden due to higher direct medical and pharmacy costs. Further investigation is needed to better understand the drivers of economic burden in patients with GPP and PPP, and how HCRU and costs are impacted by disease severity.

Defining Patient Engagement in Research: Results of a Systematic Review and Analysis: Report of the ISPOR Patient-Centered Special Interest Group.

OBJECTIVES: Lack of clarity on the definition of "patient engagement" has been highlighted as a barrier to fully implementing patient engagement in research. This study identified themes within existing definitions related to patient engagement and proposes a consensus definition of "patient engagement in research." METHODS: A systematic review was conducted to identify definitions of patient engagement and related terms in published literature (2006-2018). Definitions were extracted and qualitatively analyzed to identify themes and characteristics. A multistakeholder approach, including academia, industry, and patient representation, was taken at all stages. A proposed definition is offered based on a synthesis of the findings. RESULTS: Of 1821 abstracts identified and screened for eligibility, 317 were selected for full-text review. Of these, 169 articles met inclusion criteria, from which 244 distinct definitions were extracted for analysis. The most frequently defined terms were: "patient-centered" (30.5%), "patient engagement" (15.5%), and "patient participation" (13.4%). The majority of definitions were specific to the healthcare delivery setting (70.5%); 11.9% were specific to research. Among the definitions of "patient engagement," the most common themes were "active process," "patient involvement," and "patient as participant." In the research setting, the top themes were "patient as partner," "patient involvement," and "active process"; these did not appear in the top 3 themes of nonresearch definitions. CONCLUSION: Distinct themes are associated with the term "patient engagement" and with engagement in the "research" setting. Based on an analysis of existing literature and review by patient, industry, and academic stakeholders, we propose a scalable consensus definition of "patient engagement in research."

An Algorithm to Characterize a Dementia Population by Disease Subtype.

PURPOSE: Identification of Alzheimer disease and related dementias (ADRD) subtypes is important for pharmacologic treatment and care planning, yet inaccuracies in dementia diagnoses make ADRD subtypes hard to identify and characterize. The objectives of this study were to (1) develop a method to categorize ADRD cases by subtype and (2) characterize and compare the ADRD subtype populations by demographic and other characteristics. METHODS: We identified cases of ADRD occurring during 2008 to 2014 from the OptumLabs Database using diagnosis codes and antidementia medication fills. We developed a categorization algorithm that made use of temporal sequencing of diagnoses and provider type. RESULTS: We identified 36,838 individuals with ADRD. After application of our algorithm, the largest proportion of cases were nonspecific dementia (41.2%), followed by individuals with antidementia medication but no ADRD diagnosis (15.6%). Individuals with Alzheimer disease formed 10.2% of cases. Individuals with vascular dementia had the greatest burden of comorbid disease. Initial documentation of dementia occurred primarily in the office setting (35.1%). DISCUSSION: Our algorithm identified 6 dementia subtypes and three additional categories representing unique diagnostic patterns in the data. Differences and similarities between groups provided support for the approach and offered unique insight into ADRD subtype characteristics.

Increased Health Care Utilization in Dementia Subtypes Before Diagnosis.

INTRODUCTION: Prior studies have reported higher health care utilization (HCU) leading up to diagnosis of the Alzheimer disease and related dementia (ADRD), but none have assessed variation in HCU by ADRD subtype or examined disease-specific HCU. The objectives of this study were to identify ADRD subtypes and: (1) characterize all-cause and (2) disease-specific HCU during the 3 years preceding diagnosis, and (3) determine if HCU varied by ADRD subtype. METHODS: We used data from the OptumLabs Data Warehouse 2008 to 2014 to identify ADRD subtypes (total N=36,838) using an algorithm based on temporal sequencing of diagnoses and provider type. Annual counts of all-cause and disease-specific HCU in each of the 3 years preceding ADRD diagnosis were regressed on ADRD subtypes with mild cognitive impairment (MCI) as the reference group, year, and other variables. RESULTS: HCU increased over time, was highest in the outpatient setting, and varied by ADRD subtype. Compared with MCI, highest HCU was observed in vascular and nonspecific dementia. Compared with MCI, most subtypes had elevated disease-specific HCU. DISCUSSION: Variation in HCU by ADRD subtype points to different pathways to diagnosis and patterns of use.

Predicting Diagnosis of Alzheimer's Disease and Related Dementias Using Administrative Claims.

BACKGROUND: Predictive models for earlier diagnosis of Alzheimer's disease and related dementias (ADRD) that rely on variables requiring assessment during an office visit, such as cognitive function, body mass index, or lifestyle factors, may not be broadly applicable, since that level of data may be inaccessible or inefficient. OBJECTIVE: To build a predictive model for earlier diagnosis of ADRD using only administrative claims data to enhance applicability at the health care-system level. Building on the strength of this approach and knowledge that health care utilization (HCU) is increased before dementia diagnosis, it was hypothesized that previous HCU history would improve predictive ability of the model. METHODS: We conducted a case-control study using data from the OptumLabs Data Warehouse. ADRD was defined using ICD-9-CM codes and prescription fills for antidementia medications. We included individuals with mild cognitive impairment. Cases aged ≥ 18 years with a diagnosis between 2011-2014 were matched to controls without ADRD. HCU variables were incorporated into regression models along with comorbidities and symptoms. RESULTS: The derivation cohort comprised 24,521 cases and 95,464 controls. Final adjusted models were stratified by age. We obtained moderate accuracy (c-statistic = 0.76) for the model among younger (aged < 65 years) adults and poor discriminatory ability (c-statistic = 0.63) for the model among older adults (aged ≥ 65 years). Neurological and psychological disorders had the largest effect estimates. CONCLUSIONS: We created age-stratified predictive models for earlier diagnosis of dementia using information available in administrative claims. These models could be used in decision support systems to promote targeted cognitive screening and earlier dementia recognition for individuals aged < 65 years. These models should be validated in other cohorts. DISCLOSURES: This research was supported by AstraZeneca, Global CEO Initiative, Janssen, OptumLabs, and Roche. Albrecht was supported by Agency for Healthcare Quality and Research grant K01HS024560. Perfetto is employed by the National Health Council, which accepts membership dues and sponsorships from a variety of organizations and companies. The authors declare no other potential conflicts of interest.

Pharmacological inhibition to examine the role of DGAT1 in dietary lipid absorption in rodents and humans.

Alterations in fat metabolism, in particular elevated plasma concentrations of free fatty acids and triglycerides (TG), have been implicated in the pathogenesis of Type 2 diabetes, obesity, and cardiovascular disease. Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a member of the large family of membrane-bound O-acyltransferases, catalyzes the final step in triacylglycerol formation. In the intestine, DGAT1 is one of the acyltransferases responsible for the reesterficiation of dietary TG. Following a single dose of a selective pharmacological inhibitor of DGAT1, PF-04620110, a dose-dependent inhibition of TG and vitamin A absorption postprandially was demonstrated in rodents and human subjects. In C57/BL6J mice, acute DGAT1 inhibition alters the temporal and spatial pattern of dietary lipid absorption. To understand the impact of DGAT1 inhibition on enterocyte lipid metabolism, lipomic profiling was performed in rat intestine and plasma as well as human plasma. DGAT1 inhibition causes an enrichment of polyunsaturated fatty acids within the TG class of lipids. This pharmacological intervention gives us insight as to the role of DGAT1 in human dietary lipid absorption.