RESUMO
Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. Results: In total, 25â¯099 patients with RA were identified (mean [SD] age, 56 [17] years; 19â¯469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154â¯632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152â¯326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145â¯419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15â¯797 to -8615 and -9088 to 10â¯238, respectively, all below the predefined willingness-to-pay threshold (US $48â¯555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10â¯000 iterations was 0%, 9%, and 91%, respectively. Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.
Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Análise Custo-Benefício , Leflunomida , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Leflunomida/uso terapêutico , Leflunomida/economia , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/economia , Antirreumáticos/uso terapêutico , Antirreumáticos/economia , Feminino , Masculino , Pessoa de Meia-Idade , Infliximab/uso terapêutico , Infliximab/economia , Adulto , Hong Kong , Estudos Retrospectivos , Anos de Vida Ajustados por Qualidade de Vida , Adalimumab/uso terapêutico , Adalimumab/economia , IdosoRESUMO
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 17 artigos.
Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Esteroides/uso terapêutico , Avaliação da Tecnologia Biomédica , Vitamina D/uso terapêutico , Varfarina/uso terapêutico , Ivermectina/uso terapêutico , Ceftriaxona/uso terapêutico , Cloroquina/uso terapêutico , Metotrexato/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Oseltamivir/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Infliximab/uso terapêutico , Leflunomida/uso terapêutico , Amoxicilina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Ácido Micofenólico/uso terapêuticoRESUMO
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 8 protocolos.
Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interleucinas/antagonistas & inibidores , Corticosteroides/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Leflunomida/uso terapêutico , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Bloqueadores Neuromusculares/uso terapêuticoRESUMO
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos.
Assuntos
Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Cloroquina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Interferons/uso terapêutico , Ciclosporina/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Dexmedetomidina/uso terapêutico , Lopinavir/uso terapêutico , Rituximab/uso terapêutico , Leflunomida/uso terapêutico , Hidroxicloroquina/uso terapêuticoRESUMO
OBJECTIVES: To evaluate the cost-effectiveness of treat-to-target strategies among recently diagnosed patients with rheumatoid arthritis (RA) using methotrexate (MTX) and a step-down glucocorticoid (GC) scheme (COBRA Slim) compared with (1) this combination with either sulphasalazine (COBRA Classic) or leflunomide (COBRA Avant-Garde) in high-risk patients and (2) MTX without GCs (Tight-Step-Up, TSU) in low-risk patients. METHODS: The incremental cost-utility was calculated from a healthcare perspective in the intention-to-treat population (n=379) of the 2-year open-label pragmatic randomised controlled Care in early RA trial. Healthcare costs were collected prospectively through electronic trial records. Quality-adjusted life years (QALYs) were estimated using mapping algorithms for EuroQoL-5 Dimension. Multiple imputation was used to handle missing data and bootstrapping to calculate CIs. Robustness was tested with biological disease-modifying antirheumatic drugs at biosimilar prices. RESULTS: In the high-risk group, Classic (∆k1.464, 95% CI -0.198 to 3.127) and Avant-Garde (∆k0.636, 95% CI -0.987 to 2.258) were more expensive compared with Slim and QALYs were slightly worse for Classic (∆-0.002, 95% CI -0.086 to 0.082) and Avant-Garde (∆-0.009, 95% CI -0.102 to 0.084). This resulted in the domination of Classic and Avant-Garde by Slim. In the low-risk group, Slim was cheaper (∆k-0.617, 95% CI -2.799 to 1.566) and QALYs were higher (∆0.141, 95% CI 0.008 to 0.274) compared with TSU, indicating Slim dominated. Results were robust against the price of biosimilars. CONCLUSIONS: The combination of MTX with a GC bridging scheme is less expensive with comparable health utility than more intensive step-down combination strategies or a conventional step-up approach 2 years after initial treatment. TRIAL REGISTRATION NUMBER: NCT01172639.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Leflunomida/administração & dosagem , Medição da Dor , Sulfassalazina/administração & dosagem , Idoso , Artrite Reumatoide/diagnóstico , Análise Custo-Benefício , Quimioterapia Combinada , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Amplitude de Movimento Articular/fisiologia , Indução de Remissão , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 13 artigos e 7 protocolos.
Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Metilprednisolona/uso terapêutico , Famotidina/uso terapêutico , Cloroquina/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Lopinavir/uso terapêutico , Meloxicam/uso terapêutico , Leflunomida/uso terapêutico , Hidroxicloroquina/uso terapêuticoRESUMO
A lack of understanding of specific immune defects underlying canine immune-mediated diseases hampers optimal therapy. Failure to tailor treatment to an individual's immune abnormality can result in lack of efficacy, secondary complications, added expense, and drug-potentiated adverse effects. We adopted a small-volume whole-blood flow cytometric assay to determine the effect of immunosuppressant drugs on T-lymphocyte proliferation. Using healthy dogs in this proof-of-principle study, we hypothesized that there would be dose-dependent suppression of T-lymphocyte proliferation in response to dexamethasone, cyclosporine, mycophenolic acid, and the active metabolite of leflunomide (A77 1726). Whole blood was collected from 6 healthy pet dogs and incubated for 4 d with or without the mitogens concanavalin A and lipopolysaccharide and with increasing concentrations of immunosuppressant. Samples were subsequently stained with viability dye and with antibodies against the pan-T-lymphocyte marker CD5 and the cell proliferation marker Ki67. Percentages of proliferating T-lymphocytes were determined by flow cytometry, and the 50% inhibitory concentration (IC50) was calculated. Inhibition of T-lymphocyte proliferation by the panel of immunosuppressants was shown to be dose-dependent, with marked variability among the dogs. The mean IC50 was 394.8 ± 871 (standard deviation) µM for dexamethasone, 18.89 ± 36.2 ng/mL for cyclosporine, 106.3 ± 157.7 nM for mycophenolic acid, and 3.746 ± 6.8 µM for A77 1726. These results support the use of this assay for detecting the efficacy of individual immunosuppressants used to diminish T-lymphocyte proliferation. In future, the assay may be applied to pet dogs with spontaneous immune-mediated disease to help tailor individual treatment.
Un manque de compréhension des défauts immunitaires spécifiques sous-jacents aux maladies à médiation immunitaire canines nuit à une thérapie optimale. L'incapacité à concevoir un traitement approprié à l'anomalie immunitaire d'un individu peut résulter en une perte d'efficacité, des complications secondaires, une dépense supplémentaire, et des effets secondaires indésirables induits par les médicaments. Nous avons adopté un essai de cytométrie en flux sur un petit volume de sang entier afin de déterminer l'effet de médicaments immunosuppresseurs sur la prolifération de lymphocytes-T. En utilisant des chiens en santé dans cette étude de preuve de principe, nous avons émis l'hypothèse qu'il y aurait une suppression dose-dépendante de la prolifération des lymphocytes-T en réponse à la dexaméthasone, à la cyclosporine, à l'acide mycophénolique, et au métabolite actif du leflunomide (A77 1726). Du sang entier fut prélevé de six chiens en santé et incubé pendant 4 j avec et sans les agents mitogènes concanavaline A et lipopolysaccharide et avec des concentrations croissantes d'immunosuppresseurs. Les échantillons étaient par la suite colorés avec des colorants de viabilité et des anticorps contre le marqueur pan-lymphocyte-T CD5 et le marqueur de prolifération cellulaire Ki67. Les pourcentages de lymphocytes-T proliférant étaient déterminés par cytométrie en flux, et la concentration inhibitrice 50 % (IC50) fut calculée. L'inhibition de la prolifération de lymphocytes-T par la panoplie d'immunosuppresseurs a été démontrée comme étant dose-dépendante, avec une variabilité marquée parmi les chiens. L'IC50 moyenne était 394,8 ± 871 (écart-type) µM pour la dexaméthasone, 18,89 ± 36,2 ng/mL pour la cyclosporine, 106,3 ± 157,7 nm pour l'acide mycophénolique, et 3,746 ± 6,8 µM pour le A77 1726. Ces résultats appuient l'utilisation de cet essai pour détecter l'efficacité d'immunosuppresseurs individuels utilisés pour diminuer la prolifération de lymphocytes-T. Dans le futur, cet essai pourrait être utilisé chez des chiens de compagnie avec des maladies à médiation immunitaire spontanées afin d'aider à concevoir des traitements individuels.(Traduit par Docteur Serge Messier).
Assuntos
Ciclosporina/farmacologia , Dexametasona/farmacologia , Cães , Leflunomida/metabolismo , Ácido Micofenólico/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Anti-Inflamatórios , Antibióticos Antineoplásicos/farmacologia , Antígenos CD5/genética , Antígenos CD5/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Imunossupressores/farmacologia , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Leflunomida/química , Leflunomida/farmacologia , Linfócitos T/fisiologiaRESUMO
AIMS: Teriflunomide, used globally to treat multiple sclerosis (MS) and widely subsidised for this indication including in Australia and New Zealand, is the main metabolite of leflunomide, an older immune-modulating drug. Leflunomide therefore represents a potential alternative therapy for MS. Teriflunomide is about 50-500 times more expensive than leflunomide, depending on prices in each jurisdiction. I wished to study how this situation arose. METHODS: Web search to obtain the publicly available minutes of eight international regulatory bodies that have approved teriflunomide for the governments of the US, Canada, Europe, England, Scotland, Australia (TGA and PBS) and New Zealand, and examination of the processes and minuted discussions concerning the metabolic, efficacy, toxicity and cost relationship between teriflunomide and leflunomide. RESULTS: The relationship between the two drugs and their relative efficacy or toxicity in MS was considered by three of eight agencies (Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Canadian Agency for Drugs and Technology in Health (CADTH)). The remaining agencies accepted teriflunomide applications at face value, assessed cost-effectiveness against contemporaneous drugs used for treating MS, and did not discuss the potential role of leflunomide as a therapy for MS. No agency minuted the implications of the cost difference. CONCLUSIONS: Efficacy for leflunomide in MS is likely but unproven. The sponsor presented a case for teriflunomide that was within the established procedures for drug agencies in establishing cost-effectiveness, and agencies did not stray from their normal procedures. As a result, an opportunity to decrease the cost of treating MS has been missed. Though off-label use of leflunomide is possible, this is unlikely without a publicly-funded trial to demonstrate non-inferiority with regard to efficacy and safety.
Assuntos
Crotonatos , Aprovação de Drogas , Leflunomida , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Toluidinas , Austrália , Análise Custo-Benefício , Crotonatos/economia , Crotonatos/farmacologia , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Custos de Medicamentos , Financiamento Governamental , Humanos , Hidroxibutiratos , Imunossupressores/economia , Imunossupressores/farmacologia , Leflunomida/economia , Leflunomida/farmacologia , Nova Zelândia , Nitrilas , Toluidinas/economia , Toluidinas/farmacologiaRESUMO
CONTEXTO: La artritis reumatoide (AR) es una condición crónica y progresiva que se caracteriza por la inflamación del tejido sinovial de las articulaciones. Puede causar sensibilidad y rigidez en las articulaciones, su destrucción progresiva y síntomas que incluyen dolor y fatiga. Su tratamiento implica un diagnóstico precoz e iniciar el tratamiento lo antes posible para evitar el daño articular y disminuir el deterioro en la calidad de vida. El objetivo del tratamiento debe ser alcanzar rápidamente la remisión clínica de la enfermedad y cuando no es posible, lograr la mínima actividad de la enfermedad. OBJETIVO: Analizar la evidencia disponible acerca del tratamiento de AR con medicamentos biológicos. Establecer una recomendación de diagnóstico, tratamiento y cobertura en pacientes con AR candidatos a terapia biológica. METODOLOGÍA: Se formuló una pregunta P.I.C.O. con la siguiente población como foco: pacientes con artritis reumatoide moderada / severa refractaria a DMARDs (Drogas modificadoras de la Artritits Reumatoide) no biológicos. Se realizó una búsqueda bibliográfica destinada a recuperar Guías de prácticas clínicas, Revisiones sistemáticas, informes de Evaluación de tecnologías sanitarias (ETS), Evaluaciones Económicas y/o recomendaciones de cobertura sobre drogas biológicas para el tratamiento de AR durante el período 2013-2019. Además, se planteó una estrategia para ponderar y calificar la evidencia hallada (Revisiones Sistemáticas) y de vincular la misma con la práctica clínica. El Comité Provincial de Tecnologías Sanitarias (CoPTeS) convocó a reumatólogos e inmunólogos de los hospitales de Mendoza, a fin de conocer su experiencia. Para tal fin se diseñó una planilla, que permitía a los especialistas, ponderar cuatro aspectos relevantes de la terapia: efectividad, seguridad, adherencia y costos. RESULTADOS: Se hallaron 35 documentos. Se priorizaron revisiones sistemáticas y guías de práctica clínica. En segundo plano se priorizaron informes de ETS, evaluaciones económicas y políticas de cobertura de países similares. Estos hallazgos se presentaron a los especialistas convocados. Golimumab y Tocilizumab cumplen con el mejor esquema de valoración en evidencias y preferencias clínicas (valoración de especialistas), como también de costos del tratamiento, asequible por el Ministerio de Salud, Desarrollo Social y Deportes (MSDSyD). CONCLUSIONES: El COPTES sugiere la cobertura de Golimumab y Tocilizumab para el tratamiento de AR refractaria bajo los criterios de inclusión: Pacientes adultos con AR Activa (DAS28-4 ≥ a 5,1) y Refractaria (a 3 medicamentos no biológicos, incluidos metrotexate y leflunomida, a dosis máximas, durante 6 meses) atendidos en establecimientos del MSDSyD con cobertura estatal exclusiva. El Comité debatió acerca de la importancia de que las drogas de primera línea estén disponibles para la prescripción de manera de evitar la progresión de las lesiones. El presente documento queda sujeto al uso del correcto criterio clínico y de gestión sanitaria que se maximicen los beneficios en toda la población bajo cobertura del Ministerio de Salud.(AU)
Assuntos
Artrite Reumatoide/tratamento farmacológico , Terapia Biológica/instrumentação , Leflunomida/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Análise Custo-BenefícioRESUMO
The objective of this study is to investigate whether the addition of double-filtration plasmapheresis (DFPP) to leflunomide and methotrexate repairs MRI bone erosion in patients with long-standing rheumatoid arthritis (RA). Seventy-two patients with highly active RA of > 3 years' duration were randomized to receive DFPP in addition to DMARDs (leflunomide and methotrexate) or DMARDs. Contrast-enhanced MRI of the right wrist was performed at months 0, 6, and 12. MRI bone erosion, synovitis, and bone edema were scored with validated methods. The primary endpoint was the change in MRI bone erosion over 12 months. Patients treated with DFPP in addition to DMARDs demonstrated significantly greater decrease in MRI erosion score compared with those treated with DMARDs, being 11.3 ± 9.6 at month 12, compared with 16.9 ± 8.3 in patients with DMARDs (P < 0.001), and compared with 14.4 ± 9.6 at baseline (P < 0.001). 84.2% of patients treated with DFPP in addition to DMARDs demonstrated a decrease in MRI erosion score. Synovitis and bone edema improved significantly with DFPP in addition to DMARDs compared with DMARDs at months 6 and 12. (1.05 ± 1.7 and 2.0 ± 3.9 compared with 8.0 ± 1.4 and 12.6 ± 7.9 at month 12). Patients without synovitis and bone edema reached in 55.3% among patients with DFPP in addition to DMARDs. This study demonstrated that DFPP combination therapy significantly decreased bone erosion and received the primary goal of repair of erosions through abrogating MRI inflammation (synovitis and bone edema) in long-standing RA patients with high disease activity. The findings suggest that addition of DFPP is associated with repair of erosions and further suppression of inflammation.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Isoxazóis/uso terapêutico , Articulações/diagnóstico por imagem , Imageamento por Ressonância Magnética , Metotrexato/uso terapêutico , Plasmaferese/métodos , Adulto , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/terapia , Terapia Combinada , Feminino , Humanos , Leflunomida , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Custos de Medicamentos/tendências , Imunossupressores/uso terapêutico , Leflunomida/uso terapêutico , Padrões de Prática Médica/tendências , Antirreumáticos/economia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/economia , Austrália , Produtos Biológicos/economia , Tomada de Decisão Clínica , Custos de Medicamentos/legislação & jurisprudência , Revisão de Uso de Medicamentos , Gastos em Saúde/tendências , Humanos , Imunossupressores/economia , Leflunomida/economia , Padrões de Prática Médica/economia , Padrões de Prática Médica/legislação & jurisprudência , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: In south Korea, the price of biologics has been decreasing owing to patent expiration and the availability of biosimilars. This study evaluated the cost-effectiveness of a treatment strategy initiated with etanercept (ETN) compared with leflunomide (LFN) after a 30% reduction in the medication cost of ETN in patients with active rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR). METHODS: A cohort-based Markov model was designed to evaluate the lifetime cost-effectiveness of treatment sequence initiated with ETN (A) compared with 2 sequences initiated with LFN: LFN-ETN sequence (B) and LFN sequence (C). Patients transited through the treatment sequences, which consisted of sequential biologics and palliative therapy, based on American College of Rheumatology (ACR) responses and the probability of discontinuation. A systematic literature review and a network meta-analysis were conducted to estimate ACR responses to ETN and LFN. Utility was estimated by mapping an equation for converting the Health Assessment Questionnaire-Disability Index score to utility weight. The costs comprised medications, outpatient visits, administration, dispensing, monitoring, palliative therapy, and treatment for adverse events. A subanalysis was conducted to identify the influence of the ETN price reduction compared with the unreduced price, and sensitivity analyses explored the uncertainty of model parameters and assumptions. FINDINGS: The ETN sequence (A) was associated with higher costs and a gain in quality-adjusted life years (QALYs) compared with both sequences initiated with LFN (B, C) throughout the lifetime of patients with RA and MTX-IR. The incremental cost-effectiveness ratio (ICER) for strategy A versus B was â©13,965,825 (US$1726) per QALY and that for strategy A versus C was â©9,587,983 (US$8050) per QALY. The results indicated that strategy A was cost-effective based on the commonly cited ICER threshold of â©20,000,000 (US$16,793) per QALY in South Korea. The robustness of the base-case analysis was confirmed using sensitivity analyses. When the unreduced medication cost of ETN was applied in a subanalysis, the ICER for strategy A versus B was â©20,909,572 (US$17,556) per QALY and that for strategy A versus C was â©22,334,713 (US$18,753) per QALY. IMPLICATIONS: This study indicated that a treatment strategy initiated with ETN was more cost-effective in patients with active RA and MTX-IR than 2 sequences initiated with LFN. The results also indicate that the reduced price of ETN affected the cost-effectiveness associated with its earlier use.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Etanercepte/administração & dosagem , Isoxazóis/administração & dosagem , Medicamentos Biossimilares/uso terapêutico , Análise Custo-Benefício , Custos de Medicamentos , Etanercepte/economia , Feminino , Humanos , Isoxazóis/economia , Leflunomida , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , República da CoreiaRESUMO
PURPOSE: Little is known about the transition from nonbiologic disease-modifying antirheumatic drugs (DMARDs) to biologic DMARDs or about individual nonbiologic DMARD use patterns among patients with rheumatoid arthritis (RA). This study examined time to initiation of biologic DMARDs and nonbiologic DMARD medication adherence and persistence among Texas Medicaid recipients with RA taking nonbiologic DMARDs. METHODS: In this retrospective study (July 1, 2003-December 31, 2010) of the Texas Medicaid database, patients were aged 18 to 62 years at index, were diagnosed with RA (International Classification of Diseases, Ninth Revision, Clinical Modification, code 714.xx), had no claims for nonbiologic or biologic DMARDs in the preindex period, and had a minimum of 2 prescription claims for the same nonbiologic DMARD in the postindex period. Kaplan-Meier survival analysis and log-rank tests were used to compare time to initiation of biologic DMARDs according to nonbiologic DMARD type and therapy. Adherence and persistence were examined according to nonbiologic type and therapy by using ANOVA models and χ(2), Duncan, and t tests. FINDINGS: On average, patients were 47.9 (± 10.4) years of age, mostly female (89.1%) and Hispanic (55.2%). Methotrexate (MTX) and leflunomide (LEF) users took the shortest time to initiate biologic DMARDs (207 [190] days and 188 [205] days, respectively). LEF users had the highest mean adherence of 37.5% (27.5%), which was similar to MTX users (35.7% [26.9%]), whereas dual-therapy users had the lowest mean adherence at 17.1% (14.4%). Sulfasalazine users (108 [121] days) had the lowest persistence, whereas LEF (227 [231] days) and MTX (211 [222] days) users had the longest persistence. Nonbiologic DMARD monotherapy users were more adherent than dual-therapy users (32.6% [25.8%] vs 17.1% [14.4%]). IMPLICATIONS: These results should be interpreted in light of some study limitations, such as using proportion of days covered as a proxy for adherence, not having clinical data to control for RA severity, and lack of generalizability to all US populations. Given the study findings, both clinicians and other decision makers may want to investigate the potential driving factors of initiation of biologic DMARDs to provide effective RA management and consider patient education programs to enhance medication adherence and persistence to RA medications.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adesão à Medicação , Adolescente , Adulto , Feminino , Hispânico ou Latino , Humanos , Isoxazóis/uso terapêutico , Leflunomida , Masculino , Medicaid , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Sulfassalazina/uso terapêutico , Texas , Estados Unidos , Adulto JovemRESUMO
INTRODUCTION: This study was performed to develop ultrasound composite scores for the assessment of inflammatory and structural lesions in Psoriatic Arthritis (PsA). METHODS: We performed a prospective study on 83 PsA patients undergoing two study visits scheduled 6 months apart. B-mode and Power Doppler (PD) findings were semi-quantitatively scored at 68 joints (evaluating synovia, perisynovial tissue, tendons and bone) and 14 entheses. We constructed bilateral and unilateral (focusing the dominant site) ultrasound composite scores selecting relevant sites by a hierarchical approach. We tested convergent construct validity, reliability and feasibility of inflammatory and structural elements of the scores as well as sensitivity to change for inflammatory items. RESULTS: The bilateral score (termed PsASon22) included 22 joints (6 metacarpophalangeal joints (MCPs), 4 proximal interphalangeal joints (PIPs) of hands (H-PIPs), 2 metatarsophalangeal joints (MTPs), 4 distal interphalangeal joints (DIPs) of hands (H-DIPs), 2 DIPs of feet (F-DIPs), 4 large joints) and 4 entheses (bilateral assessment of lateral epicondyle and distal patellar tendon). The unilateral score (PsASon13) compromised 13 joints (2 MCPs, 3 H-PIPs, 1 PIP of feet (F-PIP), 2 MTPs, 1 H-DIP and 2 F-DIPs and 2 large joints) and 2 entheses (unilateral lateral epicondyle and distal patellar tendon). Both composite scores revealed a moderate to high sensitivity (bilateral composite score 43% to 100%, unilateral 36% to 100%) to detect inflammatory and structural lesions compared to the 68-joint/14-entheses score. The inflammatory and structural components of the composite scores correlated weakly with clinical markers of disease activity (corrcoeffs 0 to 0.40) and the health assessment questionnaire (HAQ, corrcoeffs 0 to 0.39), respectively. Patients with active disease achieving remission at follow-up yielded greater reductions of ultrasound inflammatory scores than those with stable clinical activity (Cohen's d effect size ranging from 0 to 0.79). Inter-rater reliability of bi- and unilateral composite scores was moderate to good with ICCs ranging from 0.42 to 0.96 and from 0.36 to 0.71, respectively for inflammatory and structural sub-scores. The PsASon22 and PsASon13 required 16 to 26 and 9 to 13 minutes, respectively to be completed. CONCLUSION: Both new PsA ultrasound composite scores (PsASon22 and PsASon13) revealed sufficient convergent construct validity, sensitivity to change, reliability and feasibility.
Assuntos
Artrite Psoriásica/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Isoxazóis/uso terapêutico , Articulações/diagnóstico por imagem , Articulações/efeitos dos fármacos , Articulações/patologia , Leflunomida , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Sulfassalazina/uso terapêutico , Inquéritos e Questionários , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Tendões/diagnóstico por imagem , Tendões/efeitos dos fármacos , Tendões/patologia , Fatores de TempoRESUMO
This study aimed to develop an identification algorithm for validating the International Classification of Diseases-Tenth diagnostic codes for rheumatoid arthritis (RA) in the Korean National Health Insurance (NHI) claims database. An individual copayment beneficiaries program for rare and intractable diseases, including seropositive RA (M05), began in South Korea in July 2009. Patients registered in this system pay only 10 % of their total medical costs, but registration requires an official report from a doctor documenting that the patient fulfills the 1987 ACR criteria. We regarded patients registered in this system as gold standard RA and examined the validity of several algorithms to define RA diagnosis using diagnostic codes and prescription data. We constructed nine algorithms using two highly specific prescriptions (positive predictive value >90 % and specificity >90 %) and one prescription with high sensitivity (>80 %) and accuracy (>75 %). A total of 59,823 RA patients were included in this validation study. Among them, 50,082 (83.7 %) were registered in the individual copayment beneficiaries program and considered true RA. We tested nine algorithms that incorporated two specific regimens [biologics and leflunomide alone, methotrexate plus leflunomide, or more than 3 disease-modifying anti-rheumatic drugs (DMARDs)] and one sensitive drug (any non-steroidal anti-inflammatory drug (NSAID), any DMARD, or any NSAID plus any DMARD). The algorithm that included biologics, more than 3 DMARDs, and any DMARD yielded the highest accuracy (91.4 %). Patients with RA diagnostic codes with prescription of biologics or any DMARD can be considered as accurate cases of RA in Korean NHI claims database.
Assuntos
Algoritmos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Bases de Dados Factuais/estatística & dados numéricos , Formulário de Reclamação de Seguro/estatística & dados numéricos , Programas Nacionais de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Codificação Clínica/classificação , Quimioterapia Combinada , Feminino , Humanos , Isoxazóis/uso terapêutico , Leflunomida , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Adulto JovemRESUMO
Takayasu's arteritis (TAK) is a rare, chronic large-vessel vasculitis (LVV) that predominantly affects aorta, its major branches, and the pulmonary arteries. Segmental stenosis, occlusion, dilatation, or aneurysm formation may occur in the vessel wall during the course of the disease. The vascular involvement can be shown with different imaging modalities to make the diagnosis of TAK. Conventional angiography, the gold standard method for initial diagnosis, seems to be replaced with the new imaging modalities such as magnetic resonance angiography (MRA) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in recent years. The data coming from the new studies support that MRA and FDG-PET are also promising for the assessment of disease activity. Prognosis is possibly getting better with lower mortality in recent years; however, it is difficult to assess the widely different vascular intervention rates among the clinical series. Leflunomide, TNF-α antagonists, and tocilizumab are new options in patients resistant to conventional therapies. There is a clear need to develop a validated set of outcome measures for use in clinical trials of TAK. The OMERACT Vasculitis Working Group has taken on this task and aims to develop a core set of outcomes for LVV.
Assuntos
Arterite de Takayasu/diagnóstico , Arterite de Takayasu/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Fluordesoxiglucose F18/farmacologia , Humanos , Isoxazóis/uso terapêutico , Leflunomida , Angiografia por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos/farmacologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresAssuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Cobertura do Seguro/economia , Cobertura do Seguro/legislação & jurisprudência , Isoxazóis/economia , Isoxazóis/uso terapêutico , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/legislação & jurisprudência , Uso Off-Label/economia , Uso Off-Label/legislação & jurisprudência , Inibidores do Fator de Necrose Tumoral , Adalimumab , Idoso , Progressão da Doença , Custos de Medicamentos/legislação & jurisprudência , Quimioterapia Combinada , Medicina Baseada em Evidências/legislação & jurisprudência , Prova Pericial/legislação & jurisprudência , Feminino , Humanos , Seguro de Serviços Farmacêuticos/economia , Seguro de Serviços Farmacêuticos/legislação & jurisprudência , Isoxazóis/efeitos adversos , Leflunomida , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Prednisolona/economia , Prednisolona/uso terapêuticoRESUMO
For rheumatoid arthritis (RA) and diseases of the spondyloarthritis group (SpA) a large number of approved medications are available. Nevertheless, in Germany even for these diseases several off-label risks exist for the rheumatologist prescribing antirheumatic drugs which have recently led to a series of recourses or threats of recourse. In RA as well as SpA first of all biologicals are the target of recourse imposed mainly by health insurances. In RA monotherapy (when labeled only in combination with methotrexate), combination with leflunomide (instead of methotrexate) and dose deviations are the most important causes. In SpA TNF inhibitors are labeled only for the definite diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) leaving aside patients with severe peripheral spondyloarthritis including enthesitis which does not exactly meet the diagnostic criteria of AS and PsA. The same applies to early AS not fulfilling the 1984 New York criteria which still lacks labeled use of TNF inhibitors. In these cases, however, based on successful randomized controlled trials and changed diagnostic criteria a label extension is expected in the near future. Until then it seems suitable to apply for permission for this treatment from insurers in each case.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Seguro de Serviços Farmacêuticos/economia , Seguro de Serviços Farmacêuticos/legislação & jurisprudência , Programas Nacionais de Saúde/economia , Uso Off-Label/economia , Uso Off-Label/legislação & jurisprudência , Espondilartrite/tratamento farmacológico , Antirreumáticos/efeitos adversos , Antirreumáticos/economia , Artrite Reumatoide/economia , Produtos Biológicos/efeitos adversos , Produtos Biológicos/economia , Produtos Biológicos/uso terapêutico , Relação Dose-Resposta a Droga , Aprovação de Drogas/economia , Aprovação de Drogas/legislação & jurisprudência , Custos de Medicamentos/legislação & jurisprudência , Quimioterapia Combinada/economia , Alemanha , Humanos , Isoxazóis/economia , Isoxazóis/uso terapêutico , Leflunomida , Metotrexato/efeitos adversos , Metotrexato/economia , Metotrexato/uso terapêutico , Mecanismo de Reembolso/economia , Mecanismo de Reembolso/legislação & jurisprudência , Espondilartrite/economia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/economiaRESUMO
OBJECTIVE: To perform a modelling study on the cost-effectiveness of three outcome-directed strategies in early RA patients: Strategy 1: starting MTX monotherapy, followed by the addition of LEF, followed by MTX with addition of anti-TNF; Strategy 2: start with MTX and LEF combination followed by MTX with anti-TNF; and Strategy 3: immediate start with MTX and anti-TNF. METHODS: A validated Markov model was used to evaluate the cost-effectiveness of the three strategies. Effectiveness of the strategies was determined using daily practice data from two cohorts and used as input parameter in the model. Patients treated according to the strategies were matched for baseline 28-joint DAS (DAS-28). Using Monte Carlo simulation, expected costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained for a 5-year time horizon were calculated following both a health-care and a societal perspective. RESULTS: The percentage of patients in remission and number of QALYs were comparable between the three strategies. Starting with a combination (MTX plus LEF or anti-TNF) was more costly than starting with MTX alone. This resulted in an unfavourable incremental cost-effectiveness ratio for starting on anti-TNF vs initially MTX: health-care perspective of 138,028 and from a societal perspective of 136,150 per QALY gained over 5 years. CONCLUSION: In this modelling study, starting with MTX or anti-TNF has comparable effectiveness. However, initial anti-TNF was far more expensive than starting with MTX monotherapy. Therefore, based on this study, a treatment strategy starting with MTX monotherapy is favoured over a strategy with MTX and anti-TNF right away in early RA patients.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Custos de Medicamentos , Isoxazóis/economia , Metotrexato/economia , Idoso , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Estudos de Coortes , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Quimioterapia Combinada , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Isoxazóis/uso terapêutico , Leflunomida , Masculino , Cadeias de Markov , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/economiaRESUMO
In order to compare the efficacy and toxicity of methotrexate and leflunomide for the treatment of rheumatoid arthritis, a double-blind randomized clinical trial was carried out at the Department of Medicine, Jinnah Medical College Hospital, Korangi, Karachi. The sample size was 240 patients and the duration of the study was 1 year. The patients enrolled were randomly divided into two groups (methotrexate and leflunomide). RA activity was clinically assessed by noting changes in the four primary (tender joint count, swollen joint count, physician and patient global assessment score) and three secondary (morning stiffness, pain intensity, HAQ) clinical efficacy end-points. Data were expressed as the mean ± SD. A P value of <0.05, calculated by paired t test, was considered significant. A total of 368 subjects were enrolled in this study. Of these, 128 subjects were withdrawn during the screening phase. Of the 240 subjects who were randomized and treated, 129 received leflunomide and 111 received methotrexate. The difference between the baseline and 12 month end-point measurements of all primary clinical efficacy end-points was significantly greater in methotrexate-treated than in leflunomide-treated subjects. Both leflunomide and methotrexate resulted in significant improvements in all secondary clinical efficacy end-points after 1 year of treatment. In both treatment groups, the most common reason for withdrawal during the treatment was adverse events. The results of this study indicate that both leflunomide and methotrexate are effective drugs for the long-term treatment of RA. It was concluded that methotrexate, which is a much cheaper drug than leflunomide, is the drug of choice, especially for patients who belong to low socioeconomic groups.