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OBJECTIVES: To describe real-world use/effectiveness of pegcetacoplan (PEG) in paroxysmal nocturnal haemoglobinuria (PNH). METHODS: Data were drawn from the Adelphi PNH Disease Specific Programme™, a cross-sectional survey conducted in France, Italy, Germany, Spain and the United States from January to November 2022. Patients had a confirmed PNH diagnosis and received PEG for ≥1 month. Physicians reported patient characteristics, treatment use/satisfaction and their perception of patients' fatigue and health-related quality of life (HRQoL). Patients reported treatment satisfaction and completed questionnaires assessing fatigue, HRQoL and productivity. Descriptive statistics were reported. RESULTS: Overall, 14 physicians provided data for 61 patients who had received 1080 mg/dose PEG for 1.3-14.8 months. At data collection compared to PEG initiation: haemoglobin was 2.5 g/dL higher on average; proportion of patients with lactate dehydrogenase (LDH) ≥1.5 × upper limit of normal was reduced by 27.4%; physician-perceived fatigue was lower and HRQoL better. Physician- and patient-reported treatment satisfaction was high for >90% of patients. Physicians and patients were more satisfied with PEG than previously prescribed C5 complement inhibitors. Mean work impairment and activity impairment in the 7 days prior to data collection were 32.9% and 22.4%, respectively. CONCLUSIONS: These real-world data support the effectiveness of PEG through positive effects on haemoglobin, LDH, fatigue and HRQoL.
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Hemoglobinuria Paroxística , Péptidos Cíclicos , Calidad de Vida , Humanos , Estados Unidos , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/tratamiento farmacológico , Estudios Transversales , Resultado del Tratamiento , L-Lactato Deshidrogenasa , HemoglobinasRESUMEN
OBJECTIVES: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, non-malignant haematological disorder associated with disabling fatigue and reduced health-related quality of life. Post hoc analysis of PEGASUS phase 3 trial (NCT03500549) characterised improvements in patient-reported fatigue measured by functional assessment of chronic illness therapy-fatigue (FACIT-fatigue) instrument item-level ratings for pegcetacoplan and eculizumab for the treatment of PNH. METHODS: Item-level responder analysis was conducted on a ≥2-level change from baseline (CFB) clinically important response (CIR) for the FACIT-fatigue 13 individual items rated on a 5-level Likert scale. We evaluated ≥2-level change against the minimal clinically important difference (MCID) of the FACIT-fatigue total score (≥5 points) and clinical parameters, haemoglobin (Hb; ≥1 g/dL) and normalised absolute reticulocyte count (ARC; 30-100 pg/cells). Logistic regressions estimated baseline-to-Week-16 FACIT-fatigue item-level transitional probabilities; Kaplan-Meier analysis estimated time to FACIT-fatigue item CIR. RESULTS: Pegcetacoplan versus eculizumab was associated with significantly greater odds of Week 16 CIR across 8/13 items and on total score MCID (OR [CI] = 11.19 [3.73, 33.57]) and faster times to responses. The item-level CIR threshold also showed clinical relevance on Hb level and ARC normalization. CONCLUSIONS: Compared with eculizumab, pegcetacoplan was associated with clinically meaningful greater improvements on a majority of FACIT-fatigue items.
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Hemoglobinuria Paroxística , Humanos , Fatiga/diagnóstico , Fatiga/tratamiento farmacológico , Fatiga/etiología , Hemoglobinas , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/tratamiento farmacológico , Hemoglobinuria Paroxística/patología , Calidad de VidaRESUMEN
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a chronic progression of nonalcoholic fatty liver disease, which can negatively impact the health-related quality of life (HRQoL) of affected individuals. HRQoL in NASH has been assessed using the disease-specific Chronic Liver Disease Questionnaire for NASH (CLDQ-NASH) and the generic EuroQol EQ-5D-5L. As the performance of these instruments relative to each other is unknown, we performed a cross-walk analysis of CLDQ-NASH to EQ-5D-5L using data from a real-world NASH population. METHODS: Data were drawn from the Adelphi Real World 2019 NASH Disease Specific Programme, a cross-sectional survey of physicians and their patients in the United States. Patients with physician-diagnosed NASH completed a questionnaire that included the CLDQ-NASH and EQ-5D-5L. Mapping from CLDQ-NASH to EQ-5D-5L was done using tenfold cross-validation; performance was assessed using root-mean squared error as accuracy measure. Subgroup analyses compared performance of the models in obese versus non-obese patients and patients with versus without type 2 diabetes (T2D). RESULTS: Data from 347 patients were included in this analysis. Overall, 2172 models were tested for predicting EQ-5D-5L index score from CLDQ-NASH score. The best model for this mapping was a generalized linear model using Gaussian distribution and a power link. The best model for mapping from CLDQ-NASH domains to the EQ-5D-5L was a fractional logistic model. Models performed better at predicting upper versus lower values of EQ-5D-5L, for non-obese versus obese patients, and for patients without versus with T2D. CONCLUSION: We describe a scoring algorithm for cross-walking the CLDQ-NASH to the EQ-5D-5L enabling health status comparisons of HRQoL across studies.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Calidad de Vida , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Transversales , Encuestas y Cuestionarios , Estado de Salud , ObesidadRESUMEN
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Hemoglobinuria Paroxística/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/economía , Inactivadores del Complemento/economía , Costo de Enfermedad , Estudios Transversales , Femenino , Hemoglobinuria Paroxística/economía , Hemoglobinuria Paroxística/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic, life-threatening disease characterized by thrombosis, impaired bone marrow function, and complement-mediated hemolysis. The PEGASUS phase III clinical trial demonstrated superiority of pegcetacoplan over eculizumab regarding improvements in hemoglobin levels in patients with suboptimal response to prior eculizumab treatment. The objective of this post hoc analysis was to compare the patient-reported outcome (PRO) response rates observed among PEGASUS participants and the relationships between their PRO scores with clinical and hematological parameters. Data from the 16-week randomized, controlled (1:1 to pegcetacoplan or eculizumab) period of the PEGASUS trial included comparisons of weekly PRO measurements taken using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales. A clinically meaningful FACIT-F response was defined as an increase from baseline of ≥5 points. Convergent validity was assessed using conventional threshold correlations between FACIT-F, EORTC QLQ-C30, and laboratory parameters. A clinically meaningful improvement in FACIT-F score was seen in 72.2% of pegcetacoplan-treated patients compared to 22.9% of eculizumab-treated patients. At week 16, the FACIT-F total score correlated with hemoglobin levels (r=0.47, p< 0.0001), absolute reticulocyte count (r=-0.37, p<0.01), and indirect bilirubin levels (r=-0.25, p<0.05). Clinically meaningful improvements in pegcetacoplan-treated patients were also observed for multiple EORTC scales. Fatigue and other self-reported outcomes were correlated with clinically meaningful improvements in clinical and hematological parameters. Clinical trial registration: NCT03500549.
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Hemoglobinuria Paroxística , Fatiga/etiología , Hemoglobinas , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/tratamiento farmacológico , Humanos , Péptidos Cíclicos , Calidad de VidaRESUMEN
OBJECTIVES: To assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)-treated patients with PNH. METHODS: This was a web-based, cross-sectional survey (01FEB2021-31MAR2021) of adults with PNH treated with eculizumab (France, Germany, United Kingdom) or ravulizumab (Germany). Self-reported outcomes included: patient characteristics; patient-reported symptoms; and standardised patient-reported outcomes (e.g. Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30]). RESULTS: Among 71 included patients, 98.6% were C5i-treated for ≥3 months (88.7% ≥12 months); among those with self-reported haemoglobin (Hb) levels (n = 63), most (85.7%) were anaemic (defined as ≤12.0 g/dL). Fatigue was the most common symptom at both diagnosis (73.2%) and survey time (63.4%); there were no statistically significant differences in symptom prevalence between treatment subgroups (eculizumab vs. ravulizumab). Total FACIT-Fatigue and EORTC QLQ-C30 scores were substantially lower than European general population references, but there were no statistically significant differences between treatment subgroups. Hb-level subgroups (<10.5 g/dL vs. ≥10.5 d/dL) followed similar trends for all measures, with few significant subgroup differences. CONCLUSIONS: Results suggest that there remains a considerable burden and unmet need among C5i-treated patients with PNH that requires improved therapies.
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Hemoglobinuria Paroxística , Adulto , Costo de Enfermedad , Estudios Transversales , Fatiga/tratamiento farmacológico , Fatiga/epidemiología , Fatiga/etiología , Alemania/epidemiología , Hemoglobinuria Paroxística/complicaciones , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/tratamiento farmacológico , Humanos , Medición de Resultados Informados por el Paciente , Calidad de VidaRESUMEN
BACKGROUND: Schizophrenia is one of 15 major causes of disability worldwide and is responsible for more than USD 150 billion in annual healthcare costs in the United States. Although the burden of schizophrenia as measured by healthcare resource utilization (HRU) is known to be considerable, data generally come from claims databases or healthcare systems/payors representing only a subset of patients, such as Medicare/Medicaid recipients. A broader understanding of HRU across the schizophrenia patient population would help identify underserved groups and inform strategies for improving healthcare delivery. AIMS OF THE STUDY: This observational study examined overall HRU and the influence of sociodemographic factors in adult patients with schizophrenia receiving care in a US integrated healthcare system. METHODS: A retrospective cohort study was conducted using data from electronic medical records (EMRs). Patients were required to have at least two diagnostic codes for schizophrenia recorded in the EMR within a 12-month period from January 2009 to June 2018, and to have received active care (≥ 1 in-system healthcare visit every six months) for at least 12 months before and after the index date (the earlier of the schizophrenia diagnosis dates). Patients were followed until no longer receiving active care or the end of the study. Patient characteristics were assessed during the 12-month pre-index period, and inpatient, readmission, emergency room (ER), and outpatient visits and antipsychotic prescriptions were described during follow-up. Findings were reported overall and in subgroups by race/ethnicity, age, and sex. RESULTS: The study cohort included 2,941 patients (mean age, 48.3 years; 54.5% male, 51.8% black, 45.8% with Medicare). During the follow-up period (mean, 4.6 years), inpatient hospital stays were common, with at least one all-cause, mental health-related, or schizophrenia-related inpatient visit occurring for 48.7%, 47.3%, and 38.8% of patients, respectively. Hospital readmissions within 30 days of an all-cause inpatient visit occurred in 20.4% of patients, with 14.5% of patients readmitted within 30 days of a schizophrenia-related inpatient visit. More than two-thirds of patients had ER visits, and 40.7% had schizophrenia-related ER visits. Only 46.7% of patients with a schizophrenia-related inpatient visit and 58.5% of patients with a mental health-related inpatient visit had a 30-day outpatient follow-up visit. Subgroup analyses revealed that a larger proportion of non-Hispanic black vs non-Hispanic white patients had 30-day outpatient follow-up visits, ER visits, mental health specialist visits, and antipsychotic prescriptions. Moreover, older age was associated with fewer ER and mental health specialist visits and less use of injectable and second-generation antipsychotics, and women were less likely than men to receive antipsychotic therapy, particularly injectable medications. DISCUSSION: Patients with schizophrenia receiving care in a US integrated healthcare system had considerable acute HRU and suboptimal rates of routine and follow-up care. Inequities in schizophrenia burden and care were observed in demographic subgroups. IMPLICATIONS FOR HEALTH POLICIES: Population health management strategies focusing on efficient resource allocation and improving healthcare quality are needed to reduce the burden of schizophrenia. Differential findings by race/ethnicity, age, and sex indicate the need for optimizing approaches to care in these subgroups.
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Prestación Integrada de Atención de Salud , Esquizofrenia , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Medicare , Persona de Mediana Edad , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiología , Estados UnidosRESUMEN
OBJECTIVE: Treatment-emergent adverse events (TEAEs) in clinical trials are typically reported for the full duration of the treatment period including titration and maintenance. Drug-related central nervous system (CNS) TEAEs are common with antiseizure medications (ASMs) and can affect drug tolerability. In this report, we test the hypothesis that drug-related CNS TEAEs have early onset and decrease with time. Unlike prior ASM clinical trials, a novel design was used for brivaracetam (BRV) without initial drug titration allowing assessment of habituation to TEAEs separate from dose titration. METHODS: Data were pooled from three studies (N01252 [NCT00490035], N01253 [NCT00464269], N01358 [NCT01261325]) in adult patients (≥16â¯years of age) with focal seizures receiving BRV adjunctive therapy. This post hoc analysis reports data on the prevalence and incidence of all drug-related CNS TEAEs and all TEAEs over time in patients who received BRV doses of 50-200â¯mg/day (without titration) vs. placebo during a 12-week treatment period. RESULTS: A total of 1262 patients received the following: placebo (nâ¯=â¯459), BRV 50â¯mg/day (nâ¯=â¯200), BRV 100â¯mg/day (nâ¯=â¯353), and BRV 200â¯mg/day (nâ¯=â¯250). Both the incidence (pâ¯<â¯.0001) and prevalence (pâ¯<â¯.0001) of drug-related CNS TEAEs (all with frequencyâ¯≥â¯5%) changed across time with peak TEAEs in week 1 then significantly reducing over the first 6â¯weeks for prevalence and the first 3â¯weeks for incidence. CONCLUSIONS: Drug-related CNS TEAEs occurred early and substantially habituated over several weeks. TEAEs of ASMs might be better represented by division into early and late phases to guide clinician monitoring and patient expectations.
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Anticonvulsivantes/efectos adversos , Ensayos Clínicos Fase III como Asunto/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Pirrolidinonas/efectos adversos , Adulto , Anticonvulsivantes/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pirrolidinonas/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study was to evaluate all-cause and epilepsy-specific healthcare resource utilization and costs following lacosamide (LCM) initiation as adjunctive therapy for the treatment of epilepsy. METHODS: A noninterventional retrospective database analysis was conducted that examined patients diagnosed as having epilepsy who added LCM to existing antiepileptic drug (AED) therapy between 2009 and 2016 (the first LCM prescription was the index event). This study used a single-case design whereby patients served as their own controls. Patients were further required to have a minimum of 12â¯months of continuous eligibility before (preindex period) and after (postindex period) their index event. In the 12-month postindex period, the only allowed AED regimen change was the addition of LCM. Demographic and clinical characteristics were measured at index and during the preindex period, respectively. All-cause and epilepsy-specific healthcare resource utilization and costs were measured and compared in the pre- and postindex periods. Paired t- and McNemar's tests were conducted to assess the significant differences between pre- and postindex. Univariate analyses were used to analyze the impact of LCM on specific subpopulations. RESULTS: The study sample comprised of 2171 patients: mean (standard deviation [SD]) age: 38.9 (19.3) years; 52.6% female. Just over half (56%) of these patients were on monotherapy before adding LCM. Prior to adding LCM, 28.8% of patients had an epilepsy-specific inpatient (IP) admission, and 35.7% of patients had an all-cause IP admission, compared with 18.2% and 26.1% of patients in the post-LCM period, respectively (both pâ¯<â¯0.0001). Likewise, 35.6% of patients had an epilepsy-specific emergency room (ER) visit, and 50.0% had an all-cause ER visit prior to adding LCM, compared with 23.8% and 42.1% in post-LCM, respectively (both pâ¯<â¯0.0001). After adding LCM, one-year mean [SD] epilepsy-specific IP admission costs decreased by 42.9% ($13,647 [$52,290] to $7788 [$32,321]), and all-cause IP admission costs decreased by 38.6% ($20,654 [$72,716] to $12,688 [$46,120]) (both pâ¯<â¯0.0001). One-year epilepsy-specific mean [SD] ER costs decreased by 35.2% ($691 [$1756] to $448 [$1909]; pâ¯<â¯0.0001), and all-cause ER cost decreased by 17.8% ($1217 [$3014] to $1000 [$2970]; pâ¯<â¯0.01). CONCLUSIONS: Epilepsy-related IP hospitalizations and ER visits (indicators of seizures) were significantly reduced in patients with epilepsy 12â¯months after adding LCM as an adjunctive therapy to existing AED treatment in a real-world setting, leading to reduced healthcare resource utilization and epilepsy costs.
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Anticonvulsivantes/economía , Epilepsia/economía , Recursos en Salud/economía , Lacosamida/economía , Aceptación de la Atención de Salud , Adulto , Anticonvulsivantes/administración & dosificación , Quimioterapia Combinada , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Recursos en Salud/tendencias , Hospitalización/economía , Hospitalización/tendencias , Humanos , Lacosamida/administración & dosificación , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: The Connectors Project, a collaboration between the Epilepsy Foundation and UCB Pharma, was a multiyear project designed to improve epilepsy care in underserved communities. A core objective of the Connectors Project was to pilot new and innovative approaches to epilepsy awareness and education in rural and underserved areas, including standardized curricula for healthcare providers and patients. METHODS: A series of consensus conferences explored opportunities and barriers to epilepsy care throughout the United States including access to local Epilepsy Foundations, neurologists, and epilepsy centers. Data from QuintilesIMS™ were examined for access to newer antiepileptic drugs (AEDs)-a proxy for quality of epilepsy care-in different regions. State factors (e.g., local epilepsy foundation office, access to newer vs. older AEDs, and geographic density and diversity) were used in selecting four states as examples of rural and underserved areas to pilot the awareness and educational programs. For each state, a work team assessed challenges and opportunities, tailored educational curricula, and developed strategies for effective delivery of the educational programs. Interventions were held between June 2016 and June 2017. Interventions consisted of outreach and awareness programs, in-person health education to healthcare providers and patients/families, and digital health education. RESULTS: Michigan, Nevada, Oklahoma, and West Virginia were identified as pilot states representing geographically diverse areas, ranging from a state with a large high-density population center with several epilepsy centers and a local Epilepsy Foundation office (Michigan) to a state with predominately rural areas and a few small urban cores, two epilepsy centers, and no in-state Epilepsy Foundation office (West Virginia). State work teams tailored interventions and examined options for type, intent, ease of use, and impact. All states implemented outreach and awareness initiatives and in-person health education for patients and healthcare providers; use of digital health education was variable. Measurement of the interventions was agreed to be performed by the use of patient and physician surveys and reevaluation of data from QuintilesIMS for access to newer AEDs. CONCLUSION: Local Epilepsy Foundation offices successfully connected healthcare providers in rural and underserved areas to epilepsy education designed to enhance quality care in epilepsy. Educational opportunities for people with epilepsy and their families addressed critical gaps in accessing quality epilepsy care and self-management. Tailored and innovative educational approaches can be used to increase awareness levels and to overcome geographic challenges in reaching underserved populations. Relationship building and repeated, consistent engagement with healthcare providers and patients can assist in improving communication and self-management skills among patients with epilepsy.
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Epilepsia/terapia , Área sin Atención Médica , Innovación Organizacional , Población Rural/tendencias , Terapias en Investigación/tendencias , Anticonvulsivantes/uso terapéutico , Epilepsia/diagnóstico , Epilepsia/epidemiología , Femenino , Humanos , Masculino , Calidad de la Atención de Salud/tendencias , Encuestas y Cuestionarios , Terapias en Investigación/métodos , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: How antiepileptic drugs (AEDs) are used in the United States (US) is one proxy public health indicator for the current state of epilepsy management. The use of phenytoin, other older AEDs, and newer AEDs may act as an indicator for the quality of epilepsy practice in addition to the current American Academy of Neurology quality measures. Data on AED used by states and populations can help identify which public health interventions are necessary to improve the status of epilepsy care. The Connectors Project, a collaboration between the Epilepsy Foundation and UCB Pharma, is a multiyear project designed to improve epilepsy awareness and management in underserved communities. The objective of the first phase of the Connectors Project was to assess geographic variation in epilepsy care and identify locations in need of improved epilepsy care by initially evaluating AED use in the US. METHODS: A retrospective cross-sectional administrative claim analysis was conducted using the QuintilesIMS™ database which included US longitudinal retail prescription and office medical claims data. Patients with a confirmed epilepsy diagnosis who were prescribed AEDs were identified. Patients with an AED prescription over a 3-year period from January 2013 to December 2015 were included if they had an epilepsy diagnosis in the 2-year period before their first AED prescription in the reporting period. The percentages of patients initially prescribed phenytoin, other older AEDs (carbamazepine and valproate), and newer AEDs (eslicarbazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, topiramate) were calculated and stratified by US state and Washington, DC. Patients were considered newly treated if they had an epilepsy diagnosis code and had not received an epilepsy drug in the 1-year period preceding the first AED prescription in the reporting period. Data are reported using the moving annual total ending December 2015. RESULTS: Approximately 2.5 million US patients with epilepsy and their AED prescriptions were identified from 2013 to 2015. Predictably, states with the largest population had the highest number of patients with epilepsy who were prescribed an AED, including California, Texas, Florida, and New York. Regions with the highest total proportion of phenytoin use with a low proportion of newer AED use were Mississippi (24.4% and 53.1%, respectively) and Washington, DC (24.7% and 58.1%). Montana had the lowest proportion of phenytoin use with the highest proportion of newer AED use (7.9% and 70.4%). Among newly treated patients (N=237,347), Hawaii (39.1%) and Alaska (38.8%) had the highest percentage of phenytoin use compared with all other states. Idaho (86.1%) and Montana (84.4%) had the highest proportion of newer AED use. Washington, DC (50.9%) and Hawaii (60.9%) had the lowest proportion of patients treated with newer AEDs. North Dakota (29.6%) and Washington, DC (27.9%) had the highest rates of other older AEDs use. CONCLUSIONS: A substantial proportion of newly treated US patients with epilepsy are underserved regarding newer AED use with Mississippi and Washington, DC having the highest proportion of phenytoin use relative to newer AED use. Understanding the socioeconomic and demographic barriers for these observations is essential in planning interventions to improve the quality of life and care for patients with epilepsy, including newly treated patients. These data provide a baseline to target educational and clinical interventions for improving the quality of US epilepsy care.
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Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Calidad de la Atención de Salud , Adulto , Anciano , Estudios Transversales , Bases de Datos Factuales , Epilepsia/epidemiología , Epilepsia/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To investigate the impact of antiepileptic drug (AED) change and dose titration on the emotional well-being of patients with epilepsy. METHODS: Members of an online epilepsy community were invited to voluntarily participate in an online survey. The cross-sectional anonymous survey consisted of 31 multiple choice questions balanced in terms of variety and positivity/negativity of emotions concerning participants' most recent AED change. To substantiate survey results, spontaneous comments from epilepsy-related online forums and social media websites that mentioned participants' experiences with AED medication changes (termed passive listening statements) were analyzed and categorized by theme. RESULTS: All 345 survey participants (270 [78.3%] female; 172 [49.9%] were 26-45years old) self-reported an epilepsy/seizure diagnosis and were currently taking seizure medication; 263 (76.2%) were taking ≥2 AEDs and 301 (87.2%) had ≥1 seizure in the previous 18months. All participants reported a medication change within the previous 12months (dose increased [153 participants (44.3%)], medication added [105 (30.4%)], dose decreased [49 (14.2%)], medication removed [38 (11.0%)]). Improving seizure control (247 [71.6%]) and adverse events (109 [31.6%]) were the most common reasons for medication change. Primary emotions most associated (≥10% of participants) with an AED regimen change were (before medication change; during/after medication change) hopefulness (50 [14.5%]; 43 [12.5%]), uncertainty (50 [14.5%]; 69 [20.0%]), and anxiety (35 [10.1%]; 45 [13.0%]), and were largely due to concerns whether the change would work (212/345 [61.4%]; 180/345 [52.2%]). In the text analysis segment aimed at validating the survey, 230 participants' passive listening statements about medication titration were analyzed; additional seizure activity during dose titration (93 [40.4%]), adverse events during titration (71 [30.9%]), higher medication dosages (33 [14.3%]), and drug costs (25 [10.9%]) were the most commonly noted concerns. CONCLUSION: Although the emotional well-being of patients with epilepsy is complex, our study results suggest that participants report their emotional well-being as negatively affected by changes in AED regimen, with most patients reporting uncertainty regarding the outcome of such a change. Future research is warranted to explore approaches to alleviate patient concerns associated with AED medication changes.
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Anticonvulsivantes/uso terapéutico , Sustitución de Medicamentos/psicología , Emociones , Epilepsia/tratamiento farmacológico , Epilepsia/psicología , Percepción , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Autoinforme , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Background. A common symptom of paroxysmal nocturnal hemoglobinuria (PNH) is fatigue, which in some patients can be severe. Eculizumab (Ecu) has proven efficacy in controlling intravascular hemolysis, but commonly results in persistent anemia and fatigue. Pegcetacoplan's (Peg) efficacy was documented in the PEGASUS phase III clinical trial, showing improved hemoglobin (Hb) and patient-reported fatigue. This post-hoc analysis sought to describe this fatigue improvement related to Hb normalization using the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-F)'s individual questions to speak more directly to patients' experience and clinicians' day-to-day practice. Methods. The PEGASUS trial compared Peg with Ecu in patients who remained anemic on Ecu over 16 weeks (n = 41 and 39, for Peg and Ecu, respectively), after which all patients received Peg open label for 32 weeks ("Peg" vs. "Ecu-to-Peg" at Week 48). Hb normalization was defined as ≥12-16 g/dL for females and ≥13.6-18 g/dL for males. The FACIT-F assessed fatigue. Using the complete-case data set, Cohen's d summarized the effect sizes of the mean FACIT-F item change for both study arms from the baseline to week 16 (n = 36 and 37, for Peg and Ecu, respectively) and from the baseline to week 48 (n = 30 and 29, for Peg and Ecu-to-Peg, respectively), and for Hb-normalized patients in each study arm from the baseline to week 16 (n = 14 and 0, for Peg and Ecu, respectively) and from the baseline to week 48 (n = 10 and 12, for Peg and Ecu-to-Peg, respectively). Results. The FACIT-F scores for both arms were worse at the baseline compared to later in the trial. Peg patients reported improvements on all fatigue items at Week 16, but Ecu patients reported improvement in only one item. At Week 48, the improvement in fatigue was maintained in Peg patients, and Ecu-to-Peg patients' fatigue improved on all FACIT-F items. Hb normalization was achieved in 14 Peg patients but no Ecu patients at Week 16, and in 10 Peg and 12 Ecu-to-Peg patients, respectively, at week 48. The FACIT-F single items showing the largest change overall, and particularly in Hb-normalized patients across the study arms, were related to symptoms and social limitations. Conclusions. Peg patients reported lasting improvements in fatigue. Patients who were anemic on Ecu reported sustained improvements in fatigue with Peg treatment. Patients who had Hb normalization generally had large, clinically important improvements in fatigue items.
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BACKGROUND: NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status. METHODS: A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables. RESULTS: A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude. CONCLUSION: Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk.
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Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Estados Unidos/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Estudios de Casos y Controles , Anciano , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Factores de Riesgo de Enfermedad CardiacaRESUMEN
AIMS: This study assessed the budget impact of resmetirom as a treatment for adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis and estimated total costs for a hypothetical private payer in the United States. MATERIALS AND METHODS: A three-year budget impact analysis based on an open cohort state transition model was developed for a hypothetical one-million-member private health plan. The comparator was Standard of Care (SOC), defined as routine care for non-cirrhotic NASH patients with moderate-to-advanced liver fibrosis. Each year, the number of resmetirom treatment-eligible patients was estimated through prevalent, incident, and diagnostic rate estimates. Costs included resources incurred by the medical and pharmacy benefits of private payers, including resmetirom drug acquisition costs, diagnosis and monitoring, other medical and other prescription costs stratified by disease progression status (i.e. non-cirrhotic vs. cirrhotic/advanced liver diseases). Resmetirom adverse event management costs were included in sensitivity analysis. Drug costs were estimated based on the average wholesale acquisition cost as of March 2024. Other costs were based on published sources and inflated to 2023 US dollars. Budget impact outcomes were presented in aggregate, net, and on a per-member per-month (PMPM) basis. RESULTS: Compared with a scenario without resmetirom, the introduction of resmetirom yielded results ranging from 50 to 238 treated patients, net budget impact of $2.2 to $9.5 million, and PMPM from $0.19 to $0.80 over years one and three. Net costs excluding resmetirom declined over time. In sensitivity analyses, results were most sensitive to diagnostic and epidemiologic inputs. LIMITATIONS: Market shares are based on internal forecasts, a short time horizon, average treatment effects, and other limitations common to BIMs. CONCLUSION: The adoption of resmetirom on the formulary for the treatment of non-cirrhotic NASH with moderate-to-advanced liver fibrosis resulted in a moderate increase in budget impact with declining costs related to NASH progression.
Non-alcoholic steatohepatitis (NASH) is a serious liver disease that can lead to significant liver damage, other health complications, and increased healthcare costs. As the disease progresses, patients typically experience worsening health outcomes. Until recently, there were no Food and Drug Administration (FDA) approved treatments for NASH in the United States. However, in March 2024, the FDA approved REZDIFFRA, a new drug specifically designed to treat NASH patients with moderate-to-advanced liver fibrosis (i.e. NASH with moderate-to-advanced scarring of the liver). Clinical trials have shown that REZDIFFRA can improve health outcomes in these patients.To identify patients who could benefit from REZDIFFRA and to estimate the associated costs, we developed a budget impact model. In this study, we detail the development of this model and present its findings. Our analysis revealed that, while REZDIFFRA is associated with higher overall costs, primarily due to the price of the drug itself, there are potential cost savings when considering the drug's ability to slow disease progression.
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Presupuestos , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/economía , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Cirrosis Hepática/economía , Estados Unidos , Índice de Severidad de la Enfermedad , Adulto , Progresión de la Enfermedad , Modelos Econométricos , Masculino , Análisis Costo-Beneficio , FemeninoRESUMEN
INTRODUCTION: Complement factor 5 inhibitors eculizumab and, recently, ravulizumab are standard therapies for paroxysmal nocturnal hemoglobinuria (PNH). However, some patients experience suboptimal response and may benefit from dosage adjustments. Ravulizumab is administered less frequently than eculizumab on the basis of patient's body weight. This retrospective analysis of insurance claims investigated ravulizumab dosing patterns among patients with PNH from the USA. METHODS: Patients aged ≥ 12 years with ≥ 2 ravulizumab infusions between June 21, 2019 and May 6, 2021, and ≥ 6 months of continuous clinical activity prior to first ravulizumab infusion (index date) were identified from the Symphony Health Integrated Dataverse (IDV®) database. Observed mean (standard deviation, SD) ravulizumab doses administered were reported and stratified by previous eculizumab use. Scenarios adjusting for patients' body weights (unavailable in Symphony Health IDV) based on the US general population distribution were performed to estimate percentages of patients receiving label-recommended doses. RESULTS: Among 433 patients (mean [SD] age 47 [17] years), the mean (SD) loading dose was 3316.3 (2931.7) mg, greater than the maximal label-recommended loading dose (3000 mg for patients ≥ 100 kg). The mean (SD) loading doses were 3581.3 (3673.7) mg for eculizumab-naive versus 3093.1 (2096.8) mg for eculizumab-experienced patients. Over a mean (SD) treatment period of 11.8 (6.9) months, the mean (SD) average maintenance dose was 3403.7 (1024.4) mg, falling between label-recommended maintenance dose categories (3300 mg for ≥ 60 to < 100 kg; 3600 mg for ≥ 100 kg). Estimated percentages of patients receiving label-recommended loading and maintenance doses were 23.1% and 39.2%, respectively; 59.1% and 28.4% were estimated to receive above label-recommended loading and average maintenance doses, respectively. CONCLUSION: Although limited by missing clinical characteristics including body weight, this study of ravulizumab dosing patterns in patients with PNH identified potential deviations from label-recommended dosing, warranting further investigations of treatment response to complement inhibitors in PNH.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease. Complement factor 5 (C5) inhibitors can help treat PNH symptoms; health care providers administer C5 inhibitors to patients during clinic or office visits. Eculizumab was the first C5 inhibitor approved for PNH. Some patients still experience symptoms with approved eculizumab doses and may need to receive larger or more frequent doses than recommended. The new C5 inhibitor ravulizumab offers reduced dosing frequency and is dosed on the basis of patients' body weights. This study assessed ravulizumab doses administered to patients with PNH in the USA using insurance claim records. Studied patients were 12 years or older and received two or more ravulizumab doses between June 21, 2019 and May 6, 2021. Researchers assessed ravulizumab doses administered to patients on the basis of body weight distribution of the US general population. The average first (loading) ravulizumab dose administered to 433 patients was 3316 mg. This was above the largest recommended loading dose of 3300 mg for patients weighing 100 kg (220 pounds) or more. Over nearly 12 months on average, the average maintenance dose administered was 3403 mg. Researchers estimated that larger loading doses than recommended were administered to almost 6 out of 10 patients and larger maintenance doses than recommended were administered to almost 3 out of 10 patients. This study found that larger than recommended ravulizumab doses may have been administered to some patients with PNH. More studies are needed to evaluate treatment response to complement inhibitors in patients with PNH.
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Anticuerpos Monoclonales Humanizados , Hemoglobinuria Paroxística , Humanos , Estados Unidos , Hemoglobinuria Paroxística/tratamiento farmacológico , Estudios Retrospectivos , Inactivadores del Complemento/uso terapéutico , Peso CorporalRESUMEN
Introduction: Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease worldwide. Therapies are under development for nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, such that the prevalence of NASH with liver fibrosis, which is likely to require treatment, may be of interest to healthcare decision makers. Noninvasive tests are used in initial screening for NASH, as well as in observational studies of NASH prevalence. However, existing evidence does not address how estimated prevalence varies with different noninvasive tests. This analysis estimated the prevalence of NASH among US adults and assessed variation with different noninvasive tests. Methods: A cross-sectional analysis was conducted using the 2017-March 2020 National Health and Nutrition Examination Survey cycle. Participants with presumed NAFLD (steatosis and without alternative causes of liver disease) were identified, among whom NASH was predicted based on FAST score, Fibrosis-4 (FIB-4), and AST-to-Platelet Ratio Index (APRI) cutoffs across 11 scenarios. Among NASH participants, fibrosis stages were explored based on distribution across the spectrum of liver-stiffness measurements. Results: Among participants with complete data for the analysis (N=6969), prevalence of presumed NAFLD was 25.6%. Within presumed NAFLD, prediction of NASH using imaging-based NIT cutoffs yielded estimated prevalence of 1.3%-4.8% (3.3 million-12.2 million) based on FAST score cutoffs from 0.35-0.67. Using biomarker-based NIT cutoffs yielded estimated prevalence of 0.4%-12.3% (1.0 million-14.5 million) based on FIB-4 cutoffs from 0.90-2.67, and 0.1%-1.9% (0.2-5.0 million) based on APRI cutoffs from 0.50-1.50. Conclusion: Prevalence of NASH among US adults was estimated to range from 1.3% to 4.8% when predicted using imaging-based noninvasive test values for participants with presumed NAFLD, generally aligning with estimates in the literature of prevalence of biopsy-confirmed NASH. Use of biomarker-based noninvasive test values for prediction of NASH yielded a wider range of estimates with FIB-4, and a considerably lower range of estimates with APRI.
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European Society for Blood and Marrow Transplantation (EBMT) hematologic response categories comprehensively assess complement inhibitor responses in patients with paroxysmal nocturnal hemoglobinuria (PNH). Using data from the 16-week randomized controlled period of the phase 3 PEGASUS trial (N = 80), we estimated the treatment cost per responder by the EBMT response category for pegcetacoplan and eculizumab in adults with PNH and a suboptimal response to eculizumab. Average drug costs per responder, number needed to treat, and incremental drug costs per responder were estimated using dosages administered during the trial (base case). A US payer perspective (2020 US dollars) was used. Scenario analyses were conducted for various costs, dosages, treatment durations, patient populations, and settings. In total, 30 of 41 (73%) who switched to pegcetacoplan and 2 of 39 (5%) patients who continued eculizumab had a good, major, or complete response (good-to-complete responders) at Week 16. Average weekly drug costs per good-to-complete responder were USD 15,923 with pegcetacoplan and USD 216,100 with eculizumab; average weekly drug costs per patient were USD 11,651 and USD 11,082, respectively. Average drug costs per good-to-complete responder with pegcetacoplan were similar across complement inhibitor-naïve populations and were consistently lower than with eculizumab. Switching from eculizumab to pegcetacoplan allowed more patients with a suboptimal response to attain a good-to-complete response at lower costs. These results apply to patients with a suboptimal response to prior eculizumab treatment only.
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BACKGROUND: Nonalcoholic steatohepatitis (NASH) is characterized by inflammation and hepatocellular damage caused by accumulation of fat in the liver. Resmetirom (MGL-3196) is an orally administered, small-molecule, liver-targeted, selective thyroid hormone receptor-ß agonist. This early analysis explored the potential cost effectiveness of resmetirom for the treatment of NASH from a US commercial payer perspective. METHODS: An early economic model was developed to reflect the clinical pathways typically followed by patients with NASH and liver fibrosis. Use of resmetirom, compared with placebo, was assessed. The Markov model structure was informed by a previous modeling study and a randomized, double-blind, placebo-controlled, phase II trial of resmetirom. Costs and outcomes were assessed over a lifetime time horizon with results presented in terms of cost per quality-adjusted life-year (QALY) gained. RESULTS: Resmetirom treatment resulted in increased costs of US$66,764 per patient, while increasing QALYs by 1.24. The incremental cost-effectiveness ratio was US$53,929 per QALY gained, indicating resmetirom treatment would potentially be cost effective at a willingness-to-pay (WTP) threshold of US$100,000. Results indicated that resmetirom would reduce the lifetime number of cases of decompensated cirrhosis (- 87), hepatocellular carcinoma (- 59), and liver transplants (- 30) per 1,000 patients compared with placebo. Resmetirom treatment remained cost effective at a US$100,000 WTP threshold up to a daily price point of US$72.00. CONCLUSION: Resmetirom is a potentially cost-effective treatment option for patients with NASH and liver fibrosis based on an analysis performed from a US commercial payer perspective. Future economic analyses of the technology should, however, focus on overcoming the limitations of existing modeling methodology.
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Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. Data were extracted from TriNetX Dataworks Network and included patients with a PNH diagnosis between 1 January 2010, and 20 August 2021. Patients were stratified into three cohorts based on their C5i usage: eculizumab, ravulizumab (prior eculizumab), and ravulizumab (eculizumab naïve). Hematological markers (hemoglobin [Hb], lactate dehydrogenase [LDH], and absolute reticulocyte count [ARC]) and relevant clinical events (e.g., breakthrough hemolysis [BTH], complement-amplifying conditions [CAC], thrombosis, infection, and all-cause mortality) were captured any time within 12 months post-index treatment. Of the 143 (eculizumab), 43 (ravulizumab, prior eculizumab), and 33 (ravulizumab, eculizumab naïve) patients, mean age across cohorts was 42-51 years, 55-61% were female, 63-73% were White, and 33-40% had aplastic anemia. Among all cohorts 12 months post-C5i treatment, 50-82% remained anemic, 8-32% required ≥1 transfusion, and 13-59% had BTH, of which 33%-54% had CACs. Additionally, thrombosis was seen in 7-15% of patients, infection in 20-25%, and mortality in 1-7%. These findings suggest many C5i-treated patients experience suboptimal disease control.