Eficacia y seguridad de rituximab más corticoides sistémicos en pacientes adultos con pénfigo vulgar moderado a severo refractario o no tributario a tratamiento convencional con agentes inmunosupresores más corticoides sistémicos / Efficacy and safety of rituximab plus systemic corticosteroids in adult patients with moderate to severe pemphigus vulgaris refractory or not amenable to conventional treatment with immunosuppressive agents plus systemic corticosteroids

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución N°111-IETSI-ESSALUD-2021 del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), se ha elaborado el presente dictamen, el cual expone la evaluación de la eficacia y seguridad de rituximab en pacientes adultos con pénfigo vulgar refractario a tratamiento convencional, en adyuvancia a corticoides sistémicos. Así, los siguientes médicos especialistas de la institución : Cindy Rodríguez Arbi, Juan Cavero Guardamino, José Catacora Cama, y Edward Alca Villarroel (médicos dermatólogos del Servicio de Dermatología del Hospital Nacional Guillermo Almenara Irigoyen de la Red Prestacional Almenara); María Pajuelo Levano, Adeliza Manrique Vera, y Celia Moisés Alfaro (médicos dermatólogos del Servicio de Dermatología del Hospital Nacional Edgardo Rebagliati Martins de la Red Prestacional Rebagliati) enviaron al IETSI las solicitudes de aprobación de uso del producto farmacéutico rituximab no incluido en Petitorio Farmacológico de EsSalud siguiendo la Directiva N°003-IETSI-ESSALUD-2016. ASPECTOS GENERALES: El pénfigo vulgar (PV) es una enfermedad autoinmune poco común, caracterizada por la presencia de ampollas intraepidérmicas extensas en las membranas mucosas y la piel. A nivel mundial, se han informado tasas de incidencia anual de entre 0.1 y 0.5 por 100,000 personas (M. Hertl and Sitaru 2022). El PV se caracteriza por la presencia de autoanticuerpos IgG dirigidos contra cadherinas dependientes de calcio: la desmogleína 3 y la desmogleína 1. La acantólisis (pérdida de la adhesión intercelular con formación consiguiente de ampollas epidérmicas) es el resultado de la inhibición de la función de las desmogleínas por la unión a los autoanticuerpos IgG que causa un descenso de la adhesión intercelular (M. Hertl and Sitaru 2022). El diagnóstico del PV se realiza por biopsia cutánea con pruebas de inmunofluorescencia y enzimoinmunoensayo inmunoadsorbente (ELISA) (M. Hertl and Sitaru 2022). METODOLOGÍA: Se realizó una búsqueda sistemática utilizando las bases de datos PubMed, Cochrane Library y LILACS. Además, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo el Scottish Medicines Consortium (SMC), el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institute for Quality and Efficiency in Health Care (IQWiG), el Instituto de Evaluación Tecnológica en Salud de Colombia (IETS), la Comissáo Nacional de Incorpornáo de Tecnologias no Sistema Único de Saúde (CONITEC), entre otros. Asimismo, se revisó la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en dermatología, tales como: la American Academy of Dermatology (AAD), la British Association of Dermatologists (BAD), la European Academy of Dermatology and Venereology (EADV) y la International Pemphigus and Pemphigoid Foundation (IPPF). Adicionalmente, se hizo una búsqueda en las páginas web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.gov/) y de la International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados. RESULTADOS: La búsqueda de literatura permitió identificar cuatro publicaciones: una GPC realizada por la BAD (Harman et al. 2017); una ETS elaborada por el Servicio Nacional de Salud (NHS, por sus siglas en inglés) de Inglaterra (NHS England 2016); y dos publicaciones del ECA Ritux 3 (Joly et al. 2017; Chen et al. 2020). CONCLUSIÓN: Por todo lo expuesto, el IETSI aprueba el uso de rituximab más corticoides sistémicos en pacientes adultos con pénfigo vulgar moderado a severo refractario o no tributario a tratamiento convencional con agentes inmunosupresores (azatioprina y micofenolato de mofetilo) más corticoides sistémicos, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, sus condiciones de uso se encuentran establecidas en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tempo.

The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States.

BACKGROUND AND OBJECTIVES: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active-Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan-Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. RESULTS: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. CONCLUSIONS: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

Fixed-dose administration and pharmacokinetically guided adjustment of busulfan dose for patients undergoing hematopoietic stem cell transplantation: a meta-analysis and cost-effectiveness analysis.

This study aims to evaluate the efficacy, safety, and long-term cost-effectiveness of fixed-dose busulfan (Bu) administration and pharmacokinetically (PK) guided adjustment of Bu dose for patients who underwent hematopoietic stem cell transplantation. The efficacy and safety of both dosing strategies were compared using a systematic review and meta-analysis. A Markov model was used in estimating relevant cost and health outcomes from the perspective of the health system. The primary outcomes of interest were lifetime cost, quality adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratio (ICER) in dollar per QALY gained. Results showed that progression-free survival and overall survival in the PK-guided group were higher than that in the fixed-dose group, and the PK-guided group was associated with low non-relapse mortality and relapse rate. In contrast to safety, the incidence of acute graft-versus-host disease (GVHD) was the same in the two groups (P > 0.05). Cost-effectiveness analysis showed that the QALY of the PK-guided group (12.8135 QALYs and $582,475.07) increased by 2.0609 relative to that in the fixed-dose group (10.7526 QALYs and $562,833.20), and the ICER was $9530.72/QALY. One-way and probability sensitivity analyses confirmed the reliability of the results. In conclusion, the PK-guided approach has higher efficacy and is safer.

Cost minimization analysis of mainstay treatments in cutaneous lupus erythematous.

Cutaneous lupus erythematosus (CLE) can be treated with multiple oral immunosuppressants but cost analyses of these treatments are lacking. We aimed to assess the relative cost difference between various oral medications for CLE using a cost-minimization analysis. Annual direct costs for 10 oral medications used in CLE were calculated including cost of medications and patient monitoring, which include office visits, laboratory and radiological studies, and procedures. Medication costs were taken from the National Average Drug Acquisition Cost calculated by the Centers of Medicare and Medicaid Services or the Average Wholesale Price. Monitoring guidelines were obtained from expert consensus and FDA-approved recommendations. Methotrexate had the lowest total direct cost ($899.31), followed by hydroxychloroquine ($1007.38), mycophenolate mofetil ($1162.12), azathioprine ($1193.71), chloroquine ($2525.01), dapsone ($2750.68), cyclosporine ($2976.32), thalidomide ($75,831.44), and lenalidomide ($316,104.03). For medications used for CLE patients, the medication cost contributes the most to differences between direct costs. Limitations include insufficient patient outcome data to ascertain medication efficacy, exclusion of cost of medication-related adverse events and hospitalizations, and medication cost data not reflecting all payers. Clinicians can use this data to help discern which medication to prescribe CLE patients with financial constraints and reduce healthcare spending.

The effectiveness and value of belimumab and voclosporin for lupus nephritis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Pearson is employed by ICER. Through their affiliated institutions, Tice, Mandrik, Thokala, and Fotheringham received funding from ICER for the work described in this summary.

Emerging treatments for lupus nephritis: health equity considerations in clinical research and coverage.

DISCLOSURES: No funding was received for the writing of this commentary. The authors report no conflicts of interest.

Cost-effectiveness of once-daily vs twice-daily tacrolimus among Hispanic and Black kidney transplant recipients.

BACKGROUND: Tacrolimus is a first-line immunosuppressive therapy to prevent rejection and graft failure in kidney transplant recipients. Once-daily extended-release tacrolimus tablets (LCPT) have been shown to be efficacious, particularly for Hispanic and Black patient subpopulations who are rapid metabolizers, but is more costly than twice-daily immediate-release tacrolimus (IR-Tac). OBJECTIVE: To evaluate the cost-effectiveness of LCPT during the first year of treatment vs IR-Tac in kidney transplant recipients who are Hispanic or Black. METHODS: A decision analytic model from a US payer perspective was developed using (1) subgroup outcomes data pooled from two phase 3 clinical trials that compared LCPT and IR-Tac, and (2) direct costs from real-world data sources (ie, costs of LCPT and IR-Tac treatments, biopsy-proven acute rejection, treatment-related serious adverse events [SAEs], graft failure, and consequent dialysis). The primary outcome was cost per successfully treated patient, defined as having a functioning graft after 1 year and without treatment-related SAEs. Probabilistic sensitivity analyses established distributions for cost and outcomes estimates, and a series of one-way sensitivity analyses identified parameters that had the most effect on results. RESULTS: Total overall cost for the Hispanic group was $14,765 for LCPT and $12,416 for IR-Tac, and total cost in the Black group was $16,626 for LCPT and $9,871 for IR-Tac. Total overall effectiveness of LCPT and IR-Tac was 88.32% and 84.75% in the Hispanic group and 93.24% and 85.78% in the Black group, respectively. The incremental cost-effectiveness ratio (ICER) for using LCPT over IR-Tac during the first year of treatment in the Hispanic group was $65,643 per additional successfully treated patient. The ICER for the Black group was $90,458. The single parameter having the most impact on results in both groups was the probability of a treatment-related SAE in IR-Tac, which accounted for 49% of variation in results in the Hispanic group and 46% in the Black group. CONCLUSIONS: Overall results for both groups show that LCPT is incrementally more costly and more effective compared with IR-Tac, indicating a trade-off scenario. LCPT is a cost-effective strategy if a decision makers' willingness to pay for 1 additional successfully treated patient exceeds the ICER and must be weighed against the costs of graft loss, continuing dialysis, and potential retransplant. This study provides a foundation for further research to update and expand inputs as more data become available to improve real-world relevance and decision making. DISCLOSURES: This study was funded by Veloxis Pharmaceuticals, Inc., which provided clinical trial file data and nonbinding feedback on the model structure, data interpretation, clinical expertise, manuscript review, and areas of publication interest (ie, managed care). Hurwitz, Grizzle, Villa Zapata, and Malone received grant funding from Veloxis Pharmaceuticals, Inc., through University of Arizona to conduct research and analysis for this study. Tyler is employed by Veloxis Pharmaceuticals, Inc. Some of the data reported and used in this research were available from the US Renal Data System, the US Bureau of Labor Statistics, and the Agency for Healthcare Research and Quality's Healthcare Cost and Utility Project. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government.

Lessons Learned Treating Patients with Multiple Myeloma in Resource-Constrained Settings.

PURPOSE OF REVIEW: Based on personal experiences, recommendations for physicians treating patients with multiple myeloma (MM) in low- and middle-income countries (LMICs) are proposed. RECOMMENDATIONS: (1) Implement strategies to keep the patient in the best possible condition for the longest time, in addition to focusing on ways to avoid financial toxicity; (2) if lenalidomide is unavailable, start treatment with thalidomide and dexamethasone, include, if possible, bortezomib; (3) conduct an outpatient-based autologous stem cell transplantation (ASCT) in all eligible patients; (4) use thalidomide as post-ASCT maintenance treatment if lenalidomide is unavailable for the standard risk patients; (5) monitor monoclonal proteins with serum protein electrophoresis and free light chain measurements; (6) employ novel drugs in cases of relapsed or refractory disease; and (7) do not forget supportive therapy. The therapeutic recommendations to treat patients with MM are somewhat different for physicians working in LMICs, compared with those treating patients in high-income countries. These are relevant since more than 50% of the inhabitants of the world live in LMICs, thus indicating that the vast majority of patients with MM are being treated in resource-constrained settings. As time goes by, physicians may acquire the ability to analyze and express their feelings and experiences about topics in the practice of medicine in which they could have learned lessons (1). Since 1980, we have been treating patients with multiple myeloma (MM); to date, we have been personally involved in the study and treatment of more than 300 patients with this disease (2). Having gained experience dealing with MM patients in underprivileged circumstances, such as those prevailing in our country: México, having explored different ideas, treatments, and methods, and being aware of the financial implications which may impact our selection of therapeutic strategies and recommendations, we felt that it was appropriate to share in this article some of these ideas with practitioners around the world who are involved in the treatment of patients with MM in low- and middle-income countries (LMICs).

Impacto económico de las nuevas terapias orales en esclerosis múltiple / Economic impact of the new oral treatments for multiple sclerosis

INTRODUCCIÓN: La esclerosis múltiple (EM) es una enfermedad crónica del sistema nervioso central que se caracteriza por la existencia de inflamación, desmielinización, gliosis y daño axonal. La introducción de dimetilfumarato y teriflunomida ha supuesto un aumento de las alternativas terapéuticas en la primera línea de tratamiento de la EM. El objetivo de este estudio fue evaluar el impacto económico de la incorporación de estas nuevas terapias orales en la Unidad de Referencia (CSUR) del Hospital Universitario Puerta de Hierro Majadahonda. MATERIAL Y MÉTODOS: Se realizó un estudio observacional retrospectivo en la población de pacientes diagnosticados de EM, en tratamiento con fármacos modificadores de la enfermedad durante el año 2015, y su seguimiento se prolongó hasta obtener un seguimiento medio superior a un año de tratamiento. Los datos se recogieron de la historia clínica electrónica y del programa de dispensación de medicamentos a pacientes externos y ambulantes del Servicio de Farmacia. RESULTADOS: Evaluando el coste del cambio del tratamiento en 125 pacientes desde otros fármacos a dimetilfumarato o teriflunomida y comparando con el coste que habría supuesto el mantenimiento de los tratamientos previos, el ahorro total durante el periodo de observación fue de 169.107,31 (Euro). CONCLUSIONES: Dimetilfumarato y teriflunomida, además de aportar nuevas alternativas terapéuticas, no solo no han supuesto un incremento sino, por el contrario, una disminución en los costes del tratamiento de la EM en nuestro hospital

INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients. RESULTS: Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of (Euro)169,107.31 over the study period. CONCLUSIONS: In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital

COVID-19 in hospitalised patients in Spain: a cohort study in Madrid.

Few large series describe the clinical characteristics, outcomes and costs of COVID-19 in Western countries. This cohort reports the first 1255 adult cases receiving anti-COVID-19 treatment at a Spanish hospital (1-24 March 2020). Treatment costs were calculated. A logistic regression model was used to explore risk factors on admission associated with ARDS. A bivariate Cox proportional hazard ratio (HR) model was employed to determine the HR between individual factors and death. We included 1255 patients (median age 65 years; 57.8% male), of which 92.3% required hospitalisation. The prevalence of hypertension, cardiovascular disease and diabetes mellitus (DM) was 45.1%, 31.4% and 19.9%, respectively. Lymphocytopenia (54.8%), elevated alanine aminotransferase (33.0%) and elevated lactate dehydrogenase (58.5%) were frequent. Overall, 36.7% of patients developed ARDS, 10.0% were admitted to an ICU and 21.3% died. The most frequent antiviral combinations were lopinavir/ritonavir plus hydroxychloroquine (44.2%), followed by triple therapy with interferon beta-1b (32.7%). Corticosteroids and tocilizumab were used in 25.3% and 12.9% of patients, respectively. Total cost of anti-COVID-19 agents was €511 825 (€408/patient). By multivariate analysis, risk factors associated with ARDS included older age, obesity, DM, severe hypoxaemia, lymphocytopenia, increased creatine kinase and increased C-reactive protein. In multivariate Cox model, older age (HR 1.07, 95% CI 1.06-1.09), cardiovascular disease (HR 1.34, 95% CI 1.01-1.79), DM (HR 1.45, 95% CI 1.09-1.92), severe hypoxaemia (HR 2.01, 95% CI 1.49-2.72), lymphocytopenia (HR 1.62, 95% CI 1.20-2.20) and increased C-reactive protein (HR 1.04, 95% CI 1.02-1.06) were risk factors for mortality.

Economic impact of the new oral treatments for multiple sclerosis. / Impacto económico de las nuevas terapias orales en esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients. RESULTS: Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of €169,107.31 over the study period. CONCLUSIONS: In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital.

Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.

Nonadherence to Immunosuppressive Medications Following Pediatric Kidney Transplantation Within Full Cost Coverage Health System: Prevalence and Correlates.

OBJECTIVES: Pediatric patients are at higher risk of nonadherence to immunosuppressive medication after kidney transplant and the resulting adverse outcomes. Factors associated with nonadherence vary, which follow an epidemiological framework and according to health system patterns. The Brazilian public health system covers all costs of kidney transplant, including immunosuppressive medications. We aimed to assess the prevalence and correlates of nonadherence to immunosuppressive medications in a pediatric kidney transplant population who received free access to immunosuppressive medications within the health care system. MATERIALS AND METHODS: In this single-center crosssectional study, we studied a convenience sample of 156 outpatients (< 18 years old) who were a minimum of 4 weeks posttransplant. Implementation nonadherence to immunosuppressive medications was measured by the 4 questions of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Multilevel correlates to non - adherence (patient, micro, and macro levels) were assessed. RESULTS: In our patient population, 61% were males, mean age was 13.6 ± 3.1 years, 77% were adolescents, and 84% received organs from deceased donors. We found that 33% were nonadherent to immuno - suppressive medications, mainly in timing (25%) and taking (10.9%) dimensions. Being an adolescent (odds ratio: 2.66; CI, 1.02-6.96), religion other than Catholic or Protestant (odds ratio: 4.33; CI, 1.13-16.67), and family income higher than 4 reference wages (odds ratio: 3.50; CI, 1.14-10.75) were factors associated with nonadherence. CONCLUSIONS: In our patient population of mostly adolescents, one-third displayed nonadherence to immunosuppressants. Unexpectedly, a higher economic profile, potentially representing better previous access to health care, was independently associated with nonadherence. This result highlights the need for identifying specific correlates to non - adherence before designing interventions.

Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)-Positive Breast Cancer.

Importance: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. Objective: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. Exposure: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Main Outcomes and Measures: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. Results: In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. Conclusions and Relevance: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

US Spending Associated With Transition From Daily to 3-Times-Weekly Glatiramer Acetate.

Importance: Market exclusivity for daily injections of glatiramer acetate, a disease-modifying therapy for multiple sclerosis, expired in 2015. In 2014, the manufacturer launched an alternate 3-times-weekly version that was widely adopted, sustaining market dominance of brand-name glatiramer until late 2017. Objective: To estimate excess US spending associated with the transition from daily to 3-times-weekly glatiramer. Design, Setting, and Participants: This economic evaluation estimated total US glatiramer spending from January 1, 2011, to June 30, 2019, using a national cohort from 3 data sources that collectively represent approximately 40% of the US glatiramer market: Medicare Part D, Medicaid, and a claims database of commercially insured and Medicare Advantage patients. Exposures: Calendar quarter. Main Outcomes and Measures: Outcomes were quarterly US glatiramer spending, estimated as price × use. Manufacturer list prices for generic products and estimates of net (postrebate) prices for brand-name products were used. Linear regression and interrupted time series models were used to compare spending trends in 3 periods: before generic competition (2011-2015), during generic competition for daily glatiramer (2015-2017), and during generic competition for daily and 3-times-weekly glatiramer (2017-2019). Results: From 2011 to 2015, US glatiramer spending increased to $962 million per quarter and did not decrease with generic competition of only daily glatiramer (2015-2017). After generic competition began for 3-times-weekly glatiramer in 2017, prices decreased by 47% to 64%, and spending decreased to $508 million per quarter in 2019 (P < .001 for slope). The delay in decreased spending from 2015 to 2017 was associated with excess spending of $4.3 billion to $6.5 billion. Conclusions and Relevance: These findings suggest that 2.5 years of delayed generic competition related to introduction of a new version of branded glatiramer acetate was associated with $4.3 billion to $6.5 billion in excess spending. Extended market exclusivity from introducing a new version of an existing brand-name drug can yield manufacturer returns out of proportion to the level of investment or risk involved; more limited incentives could encourage incremental innovations to existing drugs at a lower societal cost.

Psoriatic arthritis treatment patterns and costs among pharmacologic treatment-naïve patients.

OBJECTIVES: Pharmacologic treatment for psoriatic arthritis (PsA) includes traditional oral small molecules (OSMs), tumor necrosis factor inhibitors (TNFis), and newer oral therapies such as a phosphodiesterase-4 (PDE4) inhibitor and a Janus kinase inhibitor. We aimed to describe treatment patterns and health care costs for treatment-naïve patients with active PsA initiating pharmacologic treatment. STUDY DESIGN: This was an observational, retrospective study. METHODS: We assessed treatment patterns and health care costs from the IBM MarketScan Research databases. We calculated costs during the 12-month follow-up period for inpatient and outpatient medical health care, including outpatient prescription costs. RESULTS: A total of 3491 patients were identified for the study. Incident therapies included OSMs methotrexate (58.3%), sulfasalazine (9.8%), hydroxychloroquine (2.3%), and other OSMs (1.9%); TNFis adalimumab (12.3%), etanercept (8.6%), infliximab (1.9%), and other TNFis (1.4%); and the PDE4 inhibitor apremilast (2.6%). Persistence ranged from 15.2% to 34.6% with OSM monotherapy and from 42.9% to 58.2% with TNFi monotherapy. Percentage of patients with a gap of at least 60 days in therapy ranged from 42.9% to 48.5% with OSMs and from 17.9% to 29.9% with TNFis. Mean first-line unadjusted per-patient per-month total health care costs for OSMs ranged from $1029 to $1456 and mean total health care costs ranged from $19,173 to $25,013. Mean unadjusted per-patient per-month total health care costs for TNFis ranged from $4203 to $7063 and mean total health care costs ranged from $45,635 to $60,933. CONCLUSIONS: Although patients using OSMs had generally lower total health care costs, they also had the highest rates of treatment modifications such as low persistence and medication gaps of at least 60 days.

Prevalence and Correlates of Cost-Related Medication Nonadherence to Immunosuppressive Drugs After Heart Transplantation: The International Multicenter Cross-sectional Bright Study.

BACKGROUND: Cost-related medication nonadherence (CRMNA) refers to not taking medications as prescribed because of difficulties paying for them. OBJECTIVES: The aims of this study were (1) to assess the prevalence of CRMNA to immunosuppressants in heart transplant recipients internationally and (2) to determine multilevel correlates (patient, center, and healthcare system levels) of CRMNA. METHODS: Using data from the cross-sectional international BRIGHT study, applying multistaged sampling, CRMNA was assessed via 3 self-report items in 1365 patients from 36 heart transplant centers in 11 countries. Cost-related medication nonadherence was defined as any positive answer on any of the 3 items. Healthcare system-level (ie, insurance coverage, out-of-pocket expenditures) and patient-level (ie, intention, perceived financial burden, cost as a barrier, a health belief regarding medication benefits, cost-related self-efficacy, and demographic factors) CRMNA correlates were assessed. Correlates were examined using mixed logistic regression analysis. RESULTS: Across all study countries, CRMNA had an average prevalence of 2.6% (range, 0% [Switzerland/Brazil] to 9.8% [Australia]) and was positively related to being single (odds ratio, 2.29; 95% confidence interval, 1.17-4.47), perceived financial burden (odds ratio, 2.15; 95% confidence interval, 1.55-2.99), and cost as a barrier (odds ratio, 2.60; 95% confidence interval, 1.66-4.07). Four protective factors were identified: white ethnicity (odds ratio, 0.37; 95% confidence interval, 0.19-0.74), intention to adhere (odds ratio, 0.44; 95% confidence interval, 0.31-0.63), self-efficacy (odds ratio, 0.54; 95% confidence interval, 0.43-0.67), and belief about medication benefit (odds ratio, 0.70; 95% confidence interval, 0.57-0.87). Regarding variability, 81.3% was explained at the patient level; 13.8%, at the center level; and 4.8%, at the country level. CONCLUSION: In heart transplant recipients, the CRMNA prevalence varies across countries but is lower than in other chronically ill populations. Identified patient-level correlates are novel (ie, intention to adhere, cost-related barriers, and cost-related self-efficacy) and indicate patient-perceived medication cost burden.

The fiscal consequences of public health investments in disease-modifying therapies for the treatment of multiple sclerosis in Sweden.

Background and aims: The economic consequences of multiple sclerosis (MS) are broader than those observed within the health system. The progressive nature suggests that people will not be able to live a normal productive life and will gradually require public benefits to maintain living standards. This study investigates the public economic impact of MS and how investments in disease-modifying therapies (DMTs) influence the lifetime costs to government attributed to changes in lifetime tax revenue and disability benefits based on improved health status linked to delayed disease progression.Methods: Disease progression rates from previous MS Markov cohort models were applied to interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab using a public economic framework. The established relationship between expanded disability status scale and work-force participation, annual earnings, and disability rates for each DMT were applied. Subsequently, we assessed the effect of DMTs on discounted governmental costs consisting of health service costs, social insurance and disability costs, and changes in lifetime tax revenues.Results: Fiscal benefits attributed to informal care and community services savings for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were SEK340,387, SEK486,837, SEK257,330, and SEK958,852 compared to placebo, respectively. Tax revenue gains linked to changes in lifetime productivity for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were estimated to be SEK27,474, SEK39,659, SEK21,661, and SEK75,809, with combined fiscal benefits of cost savings and tax revenue increases of SEK410,039, SEK596,592, SEK326,939, and SEK1,208,023, respectively.Conclusion: The analysis described here illustrates the broader public economic benefits for government attributed to changes in disease status. The lifetime social insurance transfer costs were highest in non-treated patients, and lower social insurance costs were demonstrated with DMTs. These findings suggest that focusing cost-effectiveness analysis only on health costs will likely underestimate the value of DMTs.

The Effectiveness and Value of Deflazacort and Exon-Skipping Therapies for the Management of Duchenne Muscular Dystrophy.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fluetsch, Rind, and Pearson are employed by ICER. Lin reports support from ICER during work on this economic model and grants from Mount Zion Health Fund, National Institutes of Health (National Cancer Institute and National Heart, Lung, and Blood Institute), and the Tobacco-Related Diseases Research Program, unrelated to this work. Walton reports support from ICER for work on this economic model and unrelated consulting fees from Baxter.

Real-world cost of treatment for multiple sclerosis patients initiating and receiving infused disease-modifying therapies per recommended label in the United States.

Aims: The study evaluated the real-world cost of treatment in multiple sclerosis (MS) patients initiating infused disease-modifying-therapies (DMT) in the United States.Materials and Methods: This retrospective cohort study using administrative claims data included adult patients with MS initiating index infusion DMT (ocrelizumab (OCR), natalizumab (NTZ) or alemtuzumab (ATZ)) from April 2017-September 2018 with 6-months pre/12-months post-index continuous enrollment. The primary cohort included patients who had prescribed annual dosing visits indicated by the approved product label (PL): 3 OCR, 5 ATZ, and 12-13 NTZ infusion visits within the first year of initiation. Annual treatment cost was the sum of all costs on index DMT infusion visit dates. Costs were summarized for a primary and secondary cohort of patients receiving additional doses than prescribed in PL (>3 OCR, >5 ATZ, and >13 NTZ infusion visits); and an overall cohort of patients who met minimum required annual dose (≥3 OCR, ≥5 ATZ, and ≥12 NTZ), further stratified by insurance type.Results: For patients in the primary cohort (123 OCR, 18 ATZ, and 48 NTZ), mean (standard-deviation) annual cost of treatment with OCR, ATZ, and NTZ cohorts was $72,066 ($34,480), $121,053 ($51,097) and $93,777 ($38,815), respectively. Among patients initiating OCR and NTZ, 15 and 6% respectively, had additional infusion visits leading to greater costs. Mean annual costs of index infusion DMT treatment in the overall cohort (162 patients treated with OCR, 18 with ATZ, 56 with NTZ) were $80,582, $121,053, and $93,807, respectively. The mean costs for commercial enrollees were higher than those for MAPD enrollees.Limitations: Small sample size, limited population generalizability, and cost-reduction for ATZ beyond the second year need to be accounted for.Conclusions: Real-world infusion DMT treatment costs for commercially insured patients were higher than perceived expenditures based on wholesale acquisition cost and administration costs via a physician-fee schedule. Consideration of real-world costs in cost-effectiveness and treatment/coverage decisions is needed.