RESUMO
ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021 y ampliada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 97-IETSI-ESSALUD2022, se ha elaborado el presente dictamen, el cual expone la evaluación de la eficacia y seguridad de guselkumab y secukinumab en pacientes adultos con psoriasis vulgar severa, no respondedores a terapia tópica y sistémica convencional y no tributario a terapia biológica antagonista al factor de necrosis tumoral disponible en EsSalud por antecedente de neoplasia maligna, en comparación de la mejor terapia de soporte. Así, la médica Evelyn Giuliana Castro Vargas, especialista en dermatología, a través del Comité Farmacoterapéutico del Hospital Nacional Alberto Sabogal Sologuren y siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de autorización de uso del producto farmacéutico guselkumab no incluido en el Petitorio Farmacológico de EsSalud. ASPECTOS GENERALES La psoriasis es una enfermedad dermatológica inflamatoria crónica no transmisible que afecta aproximadamente del 1 % al 3 % de la población mundial (Augustin et al., 2010) con una prevalencia de alrededor del 2.5 % en el Perú (Rodríguez-Zúñiga, 2016). Esta enfermedad es considerada como un problema de salud pública y de elevada carga para la sociedad (Parisi et al., 2013), lo que se explica por su alto riesgo de morbilidad y porque deteriora la calidad de vida y la salud mental de las personas que lo padecen (Boehnoke & Schón, 2015). El fenotipo de psoriasis más común es la psoriasis vulgar, que se caracteriza por la presencia de placas eritematosas, gruesas y escamosas que se presentan mayormente en cuero cabelludo, glúteos, tronco y extremidades (codos y rodillas). La psoriasis suele clasificarse en leve, moderada y severa, según la clinimetría de las mediciones del Psoriasis Area and Severity Index (PASI), la Body surface area (BSA) y la calidad de vida medida a partir del Dermatology Life Quality Index (DLQI) (Finlay, 2015; Robinson et al., 2012). Es decir, la enfermedad severa se define por tener más de 10 puntos en el PASI, más del 10 % de la superficie corporal (BSA) afectada por la enfermedad, o más de 10 puntos en el DLQI (Strober et al., 2019). Los tratamientos para los pacientes con psoriasis vulgar severa tienen como objetivo lograr una reducción de por lo menos el 75 % o 90 % de la severidad de enfermedad inicial medida por la escala PASI (i.e. PASI75 o PASI90, respectivamente) luego de al menos tres meses de tratamiento efectivo (Belinchón Romero et al., 2021). Asimismo, se considera que, si después de 16 a 24 semanas de la aplicación de un esquema terapéutico efectivo no se ha logrado por lo menos alcanzar el PASI75 con DLQI < 5 o un PASI90, se considera que el paciente no ha respondido al tratamiento (i.e. falla terapéutica) (Aschoff et al., 2021). Así, entre los tratamientos disponibles para la psoriasis tenemos la terapia tópica que se utiliza en los casos de psoriasis leve a moderada', y la terapia sistémica, en casos de psoriasis de moderada a severa2. Dentro de la terapia sistémica, tenemos a los agentes sistémicos convencionales (metotrexato, ciclosporina o acitretina) y la terapia biológica. Ésta última se utiliza generalmente en los casos de falla al tratamiento con agentes sistémicos convencionales (Gisondi et al., 2017). Las terapias biológicas se clasifican según el mecanismo de acción, es decir, según la inhibición dirigida a citoquinas específicas del sistema inmune, tales como el factor de necrosis tumoral alfa (TNF), la interleucina (IL) 17 (IL17) y la IL23 (Fellner, 2016). METODOLOGIA: Se realizó una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad de guselkumab y secukinumab en pacientes adultos con psoriasis vulgar severa no respondedores a terapia tópica y sistémica convencional y no tributario a terapia biológica anti TNF disponibles en EsSalud por antecedente de neoplasia maligna. La búsqueda se realizó en las bases de datos bibliográficas de PubMed, The Cochrane Library, Web of Science y LILACS (Literatura Latinoamericana y del Caribe en Ciencias 'de la Salud). Asimismo, se realizó una búsqueda dentro de la información generada en las páginas web de grupos o instituciones que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como: el National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish Intercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), la Haute Authorité de Santé (HAS), el Institute for Quality and Efficiency in Health Care (IQWiG), la Comissáo Nacional de lncorporagáo de Tecnologías no Sistema Único de Saúde (CONITEC), el Institute for Clinical and Economic Review (ICER) y en la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA). Además, se realizó una búsqueda de las guías en las principales instituciones o sociedades especializadas en dermatología y en psoriasis, 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 Psoriasis Council (IPC). Adicionalmente, se llevó a cabo una búsqueda manual en el motor de búsqueda Google utilizando los términos: "Psoriasis guidelines"; revisando documentos de interés en las diez primeras páginas. Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o aún no publicados. RESULTADOS: Luego de la búsqueda bibliográfica hasta diciembre de 2022, se identificaron: una GPC de la BAD publicada en el 2020 (Smith et al., 2020); y una RS con MA en red (Sbidian et al., 2022) publicada en el 2022 que fue seleccionada como evidencia indirecta para responder a la pregunta PICO del presente dictamen. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de guselkumab en pacientes adultos con psoriasis vulgar severa, no respondedores a terapia tópica y sistémica convencional y no tributario a terapia biológica anti TNF antecedente de neoplasia maligna, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente informe 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.
Assuntos
Humanos , Psoríase/tratamento farmacológico , Metotrexato/farmacologia , Interleucinas/antagonistas & inibidores , Acitretina/farmacologia , Corticosteroides/farmacologia , Interleucina-23/antagonistas & inibidores , Inibidores do Fator de Necrose Tumoral/economia , Eficácia , Análise Custo-BenefícioRESUMO
In 2020, the anti-tumor necrosis factor (TNF) monoclonal antibody Humira® generated US$165.8 billion in cumulative sales and snatched the crown for the industry's most successful drug from Lipitor (atorvastatin). TNF-α is a major component in beneficial and disease-related inflammation and TNF-α-inhibitor biologics have gained widespread use in autoimmune diseases, such as rheumatoid arthritis (RA). Many more diseases could benefit from TNF-α inhibitors, such as Alzheimer's disease (AD) or major depression. However, the nature of TNF-α-inhibitor biologics prohibits central nervous system (CNS) applications. Moreover, high drug production costs and pricing, together with antidrug immune reactions and insufficient patient coverage, argue for the development of small-molecule drugs. Recently, drug-like orally available small molecules were described with high activity in animal disease models with activities comparable to those of antibodies.
Assuntos
Inflamação , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/química , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologiaRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease that causes joint destruction. The condition imposes a significant economic burden on patients and societies. The present study is aimed at evaluating the cost-effectiveness of Infliximab, Adalimumab, and Etanercept in treating rheumatoid arthritis in Iran. METHODS: This is a cost-effectiveness study of economic evaluation in which the Markov model was used. The study was carried out on 154 patients with rheumatoid arthritis in Fars province taking Infliximab, Adalimumab, and Etanercept. The patients were selected through sampling. In this study, the cost data were collected from a community perspective, and the outcomes were the mean reductions in DAS-28 and QALY. The cost data collection form and the EQ-5D questionnaire were also used to collect the required data. The results were presented in the form of an incremental cost-effectiveness ratio, and the sensitivity analysis was used to measure the robustness of the study results. The TreeAge Pro and Excel softwares were used to analyze the collected data. RESULTS: The results showed that the mean costs and the QALY rates in the Infliximab, Adalimumab, and Etanercept arms were $ 79,518.33 and 12.34, $ 91,695.59 and 13.25, and $ 87,440.92 and 11.79, respectively. The one-way sensitivity analysis confirmed the robustness of the results. In addition, the results of the probabilistic sensitivity analysis (PSA) indicated that on the cost-effectiveness acceptability curve, Infliximab was in the acceptance area and below the threshold in 77% of simulations. The scatter plot was in the mentioned area in 81% and 91% of simulations compared with Adalimumab and Etanercept, respectively, implying lower costs and higher effectiveness than the other two alternatives. Therefore, the strategy was more cost-effective. CONCLUSION: According to the results of this study, Infliximab was more cost-effective than the other two medications. Therefore, it is recommended that physicians use this medication as the priority in treating rheumatoid arthritis. It is also suggested that health policymakers consider the present study results in preparing treatment guidelines for RA.
Assuntos
Adalimumab/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Etanercepte/uso terapêutico , Infliximab/uso terapêutico , Adalimumab/economia , Anti-Inflamatórios não Esteroides/economia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/economia , Produtos Biológicos/economia , Análise Custo-Benefício , Estudos Transversais , Etanercepte/economia , Feminino , Humanos , Infliximab/economia , Irã (Geográfico) , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND: We aimed to examine the uptake of infliximab and etanercept biosimilars in patients with rheumatoid arthritis (RA) and its economic implication for healthcare expenditure. METHODS: Using Korean Health Insurance Review and Assessment Service National Patient Samples, we extracted RA patients who used biologic disease modifying anti-rheumatic drugs (bDMARDs) between 2009 and 2018. Descriptive statistics were used to explain the basic features of the data. We calculated the proportion of users of each bDMARD among total patients with bDMARDs half-yearly. We assessed changes in the utilization proportions of bDMARDs including 4 tumor necrosis factor inhibitors (TNFis) and 2 non-TNFis, which have been approved for RA in Korea: etanercept, infliximab, adalimumab, golimumab, tocilizumab, and abatacept, and analyzed the changes in market share of biosimilars among the bDMARDs after their introduction. Overall trends of medical costs for each bDMARD were presented over the 10-year period. RESULTS: Since the introduction of the biosimilar TNFis in 2012, the proportion of their use among bDMARDs steadily increased to 15.8% in 2018. While there has been a gradual increase in the use of biosimilar TNFis, the use of the corresponding originators has been decreasing. The introduction of biosimilar TNFis has resulted in a decrease in the medical costs of patients using either originator or biosimilar TNFis. CONCLUSION: In Korea, the proportional use of biosimilar TNFis has gradually increased since their introduction. The availability of less expensive biosimilar TNFis seems to have brought about a decrease in the medical costs of users of the originators.
Assuntos
Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/uso terapêutico , Custos de Cuidados de Saúde/estatística & dados numéricos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/economia , Etanercepte/economia , Etanercepte/uso terapêutico , Humanos , Infliximab/economia , Infliximab/uso terapêutico , República da Coreia , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/economiaRESUMO
Background There is over 10 years of clinical experience and evidence to show that biosimilar medicines can be used as safely and effectively in approved therapeutic indications as their originator biological medicines. In Ireland, biosimilar medicine uptake has been very slow, and savings to the health service will only be realised through fostering a competitive biological medicine market. Objective The objective of this study was to investigate the utilisation of biosimilars following a 'best-value biological' medicine initiative for adalimumab and etanercept in the Irish healthcare setting. Methods Data was extracted from the National High Tech claims database and High Tech ordering and management hub for the following drugs; adalimumab (Humira®, Amgevita®, Hulio®, Idacio®, and Imraldi®) and etanercept (Enbrel® and Benepali®). Main outcome measure: uptake of the best-value biological medicines. Results In June 2019, just over 90 patients had been initiated on, or switched to a best-value biological for adalimumab or etanercept. Over the next 12 months this increased to over 8500 patients. With the best-value biologicals accounting for approximately 50 % of market share in June 2020, the combined estimated savings and avoided costs are 22.7 million to date. The gain-share prescribing incentive has raised over 3.6 million for the specialties to invest back into patient care. Conclusion Against the background of a finite healthcare budget, this study shows that increasing use of biosimilars can create the financial savings and space to invest in new innovative therapies for the benefit of many patients.
Assuntos
Adalimumab/economia , Medicamentos Biossimilares , Etanercepte/economia , Inibidores do Fator de Necrose Tumoral/economia , Medicamentos Biossimilares/economia , Orçamentos , Humanos , IrlandaRESUMO
OBJECTIVE: To evaluate the sequences of tumor necrosis factor inhibitors (TNFi) and non-TNFi used by rheumatoid arthritis (RA) patients whose initial TNFi therapy has failed, and to evaluate effectiveness and costs. METHODS: Using the Truven Health MarketScan Research database, we analyzed claims of commercially insured adult patients with RA who switched to their second biologic or targeted disease-modifying antirheumatic drug between January 2008 and December 2015. Our primary outcome was the frequency of treatment sequences. Our secondary outcomes were the time to therapy discontinuation, drug adherence, and drug and other health care costs. RESULTS: Among 10,442 RA patients identified, 36.5% swapped to a non-TNFi drug, most commonly abatacept (54.2%). The remaining 63.5% cycled to a second TNFi, most commonly adalimumab (41.2%). For subsequent switches of therapy, non-TNFi were more common. Patients who swapped to a non-TNFi were significantly older and had more comorbidities than those who cycled to a TNFi (P < 0.001). Survival analysis showed a longer time to discontinuation for non-TNFi than for TNFi (median 605 days compared with 489 days; P < 0.001) when used after initial TNFi discontinuation, but no difference in subsequent switches of therapy. Although non-TNFi were less expensive for adherent patients, cycling to a TNFi was associated with lower costs overall. CONCLUSION: Even though patients are more likely to cycle to a second TNFi than swap to a non-TNFi, those who swap to a non-TNFi are more likely to persist with the therapy. However, cycling to a TNFi is the less costly strategy.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Substituição de Medicamentos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/economia , Artrite Reumatoide/imunologia , Redução de Custos , Análise Custo-Benefício , Bases de Dados Factuais , Esquema de Medicação , Custos de Medicamentos , Substituição de Medicamentos/efeitos adversos , Substituição de Medicamentos/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/economia , Estados UnidosRESUMO
In 2018, TNFα inhibitors were the highest cost drug class for Canadian public drug programs. In 2019, two Canadian provinces announced mandatory nonmedical switching policies in an attempt to reduce their costs by increasing biosimilar uptake. The national impact of similar policies across Canada is unknown. We conducted a cross-sectional analysis of monthly publicly funded prescription claims for infliximab, etanercept, and adalimumab between June 2015 and December 2019. We reported the market share of biosimilars for infliximab and etanercept in 2019 for each province and estimated the cost savings that public payers could have realized in 2019 if mandatory switching policies had been implemented across Canada, including a sensitivity analysis, which assumed that governments receive a 25% rebate on all biologics. Provincial drug programs spent CAD $991.84 million on infliximab, etanercept, and adalimumab in 2019, and, when biosimilars were available, they constituted only 15.5% of national utilization of these drugs. In British Columbia, the implementation of a mandatory switching policy for patients with rheumatic conditions increased the biosimilar market share of infliximab and etanercept by 299% (from 19.7% to 78.5%). If applied nationwide to all three biologics for all indications, we estimate such policies could lead to annual savings of between CAD $179.71 million and CAD $425.64 million nationally. The overall market share of biosimilars remains low in all provinces where mandatory switching policies have not been introduced. The cost implications of successfully increasing biosimilar uptake would be substantial, particularly as more biosimilars reach the Canadian market.
Assuntos
Produtos Biológicos/economia , Produtos Biológicos/uso terapêutico , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/uso terapêutico , Custos de Medicamentos , Substituição de Medicamentos/economia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/economia , Adalimumab/uso terapêutico , Produtos Biológicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Canadá , Redução de Custos , Análise Custo-Benefício , Estudos Transversais , Etanercepte/economia , Etanercepte/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/economia , Infliximab/economia , Infliximab/uso terapêutico , Formulação de Políticas , Saúde Pública/economia , Doenças Reumáticas/economia , Fatores de Tempo , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
OBJECTIVE: To compare direct costs and treatment utility associated with the second-line therapy with rituximab and tumour necrosis factor inhibitors (TNFis) (adalimumab, etanercept, and infliximab) in patients with Rheumatoid Arthritis (RA) using data from a prospective registry. METHODS: Health Assessment Questionnaire Disability Index (HAQ-DI) scores and RA-related healthcare resource utilization data (biologic agents and visits to rheumatologists) were extracted from a registry (Quebec, Canada) for patients with RA (n = 129) who had to discontinue a first-line TNFi and were treated with rituximab, adalimumab, etanercept, or infliximab as the second-line therapy between January 2007 and May 2016. A decision analytic model followed patients for 1 and 6 years. Treatment utility was measured as quality-adjusted life-years (QALYs) gained, which were calculated from HAQ-DI scores observed over the follow-up time. Quebec 2020 unit costs (Canadian Dollars, $) were used to value healthcare resource consumption. A probabilistic sensitivity analysis was performed with 10,000 Monte Carlo simulations to assess uncertainty around point-estimates of cost-utility. RESULTS: Over 1-year, rituximab and etanercept resulted in the effectiveness of 0.80 QALYs gained at the cost of $14,291and $18,880, respectively, and were dominant (i.e. associated with lower costs and more QALYs gained) compared to adalimumab (0.79 QALYs, $18,825) and infliximab (0.76 QALYs, $20,158). Over 6-years, rituximab (4.42 QALYs, $82,402) was dominant compared to adalimumab (4.30 QALYs, $101,420), etanercept (4.02 QALYs, $99,191), and infliximab (3.71 QALYs, $100,396). In the probabilistic analysis, rituximab was dominant over adalimumab, etanercept, and infliximab with the probability of 0.51, 0.62, and 0.65, respectively. CONCLUSION: Real-world data revealed differences between alternative biologic agents used as the second-line therapy in terms of both treatment costs for the healthcare system and utility of treatment for patients. Therefore, new guidelines on the order of selecting and switching biologic agents should be explored.
Assuntos
Antirreumáticos , Artrite Reumatoide , Rituximab , Inibidores do Fator de Necrose Tumoral , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Análise Custo-Benefício , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Rituximab/economia , Rituximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND: Spending on drugs provided by the Brazilian Public Health System (BPHS) for the treatment of rheumatoid arthritis (RA) increased substantially with the beginning of the supply of biological disease-modifying anti-rheumatic drugs (bDMARD). This study aims to perform a cost-utility analysis of the most used biological drugs for the treatment of RA in Brazil. METHODS: a Markov model was used to carry out the cost-utility analysis. The data were obtained from a prospective cohort of RA patients using adalimumab, etanercept, and golimumab in Brazil. The BPHS perspective was adopted and the time horizon was five years. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. RESULTS: golimumab was the most cost-effective drug. Etanercept was dominated by golimumab. Adalimumab presented an incremental cost-utility ratio (ICUR) of $95,095.37 compared to golimumab in five years of follow-up. These results were confirmed by sensitivity analyses. CONCLUSION: the utility among adalimumab, etanercept, and golimumab was similar and the cost was the component that most impacted the economic model. Therefore, depending on the agreed price with the drug manufacturers, the incremental cost-utility ratio may vary among them.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Modelos Econômicos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adalimumab/administração & dosagem , Adalimumab/economia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/economia , Antirreumáticos/economia , Artrite Reumatoide/economia , Brasil , Estudos de Coortes , Análise Custo-Benefício , Etanercepte/administração & dosagem , Etanercepte/economia , Feminino , Seguimentos , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral/economiaRESUMO
BACKGROUND: Ankylosing spondylitis (AS) is a form of rheumatic disease caused by chronic inflammation of the axial skeleton. Patients with AS experience significant functional limitations and reduced quality of life. Consequently, AS imposes a substantial economic burden on society due to productivity loss and work disability. Biologics, including tumor necrosis factor (TNF) inhibitors and human anti-interleukin-17A monoclonal antibody (IL-17A) agents, are effective treatment strategies in relieving symptoms and slowing down disease progression. Currently, 5 TNF inhibitors and 2 IL-17A antibody agents are approved by the FDA for the management of AS. Of these agents, there is no clear preferred agent in initial biologic therapy, although an IL-17A antibody agent or alternative TNF inhibitor agent is recommended after failure of the initial TNF inhibitor therapy. OBJECTIVE: To assess cost-effectiveness of treatment strategies with biologics, TNF inhibitor or IL-17A, in accordance with the treatment guidelines for patients with AS. METHODS: An economic patient-level simulation combining decision-tree and Markov models was constructed from the U.S. health care payer's perspective over a 10-year time horizon. The current model examined 5 treatment strategies: (1) conventional care treatment with nonsteroidal anti-inflammatory drugs, (2) 1 TNF inhibitor, (3) an IL-17A antibody agent, (4) sequential therapy with 2 TNF inhibitors, and (5) sequential therapy with a TNF inhibitor followed by an IL-17A antibody agent. Initially, treatment responses were determined after 12-week treatments. Patients who responded to treatment entered a "responders" Markov model. Patients entered a "nonresponders" Markov model if they inadequately responded to treatment. In sequential treatment strategies, patients who inadequately responded to treatment with the first TNF inhibitor received a second TNF inhibitor or an IL-17A antibody agent. Health utility was estimated based on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI) scores. The models accounted for real-world adherence to TNF inhibitor treatment. Scenario and probabilistic sensitivity analyses were performed to test the robustness and uncertainty of the model results. RESULTS: Over a 10-year time horizon and 100,000 simulated patients for each treatment strategy, base-case results produced average total discounted per-patient costs of $19,765, $130,302, $159,934, $190,553, and $179,118 and quality-adjusted life-years (QALYs) of 4.675, 5.410, 5.499, 5.919, and 5.893 for conventional care, treatment strategies with 1 TNF inhibitor, an IL-17A, 2 TNF inhibitors, and a TNF inhibitor followed by an IL-17A, respectively. The optimal treatments at willingness-to-pay (WTP) thresholds ≤ $130,813 per QALY, between $130,813 per QALY and $442,728 per QALY, and > $442,728 per QALY were conventional care and sequential treatment strategies with 1 TNF inhibitor, followed by an IL-17A agent and 2 TNF inhibitors, respectively. CONCLUSIONS: Study findings suggested that all treatment strategies with biologics, TNF inhibitors or IL-17A antibody agents, in the treatment guidelines for AS were not cost-effective at the common WTP of $100,000 per QALY. However, the sequential treatment with 1 TNF inhibitor followed by an IL-17A antibody agent was considered cost-effective at a higher WTP of $150,000 per QALY. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Primary findings of this study were presented in part at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Baltimore, MD, May 2018.
Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Modelos Econômicos , Espondilite Anquilosante/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/economia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/economia , Produtos Biológicos/economia , Análise Custo-Benefício , Árvores de Decisões , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Espondilite Anquilosante/economia , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Estados UnidosRESUMO
OBJECTIVE: The aim of the current study was to evaluate the 2-year cost-utility ratio between tapering conventional synthetic disease-modifying antirheumatic drugs (csDMARD) first followed by the tumour necrosis factor (TNF)-inhibitor, or vice versa, in patients with rheumatoid arthritis (RA). METHODS: Two-year data of the Tapering strategies in Rheumatoid Arthritis trial were used. Patients with RA, who used both a csDMARD and a TNF-inhibitor and had a well-controlled disease (disease activity score ≤2.4 and swollen joint count≤1) for at least 3 months, were randomised into gradual tapering the csDMARD first followed by the TNF-inhibitor, or vice versa. Quality-adjusted life years (QALYs) were derived from the European Quality of life questionnaire with 5 dimensions. Healthcare and productivity costs were calculated with data from patient records and questionnaires. The incremental cost-effectiveness ratio and the incremental net monetary benefit were used to assess cost effectiveness between both tapering strategies. RESULTS: 94 patients started tapering their TNF-inhibitor first, while the other 95 tapered their csDMARD first. QALYs (SD) were, respectively, 1.64 (0.22) and 1.65 (0.22). Medication costs were significantly lower in the patients who tapered the TNF-inhibitor first, while indirect cost were higher due to more productivity loss (p=0.10). Therefore, total costs (SD) were 38 833 (39 616) for tapering csDMARDs first, and 39 442 (47 271) for tapering the TNF-inhibitor (p=0.88). For willingness-to-pay (WTP) levels <83 800 tapering, the csDMARD first has the highest probability of being cost effective, while for WTP levels >83 800 tapering the TNF-inhibitor first has the highest probability. CONCLUSION: Our economic evaluation shows that costs are similar for both tapering strategies. Regardless of the WTP, tapering either the TNF-inhibitor or the csDMARD first is equally cost effective. TRIAL REGISTRATION NUMBER: NTR2754.
Assuntos
Antirreumáticos/administração & dosagem , Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Análise Custo-Benefício , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/economia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Método Simples-Cego , Exacerbação dos Sintomas , Resultado do TratamentoRESUMO
BACKGROUND: Evidence supports therapeutic drug monitoring (TDM) in improving efficacy and cost-effectiveness of anti-TNF therapy in inflammatory bowel disease (IBD). Data on perceptions and barriers to TDM use are limited and no data are available from India. Our objective was to assess clinicians' attitudes and barriers to TDM use in IBD. METHODS: A 16-question survey was distributed to members of the Indian Society of Gastroenterology. Information on clinician characteristics, demographics, use and barriers towards TDM with anti-TNFs was collected. Logistic regression was used to predict factors influencing TDM use. RESULTS: Two hundred and forty-two respondents participated (92.5% male); 83% were consultant gastroenterologists. Of 104 respondents meeting inclusion criteria (treating > 5 IBD patients and at least 1 with an anti-TNF per month), complete responses were available for 101 participants. TDM was utilized by 20% (n = 20) of respondents. Of them, 89.5% (n = 17) used TDM for secondary loss of response; 73.7% (n = 14) for primary non-response and 5.3% (n = 1) proactively. Barriers to TDM use were cost (71.2%), availability (67.8%), time lag in results (58.7%) and the perception that TDM is time-consuming (45.7%). Clinicians treating > 30 IBD patients were more likely to check TDM (OR = 4.9, p = 0.02). Of 81 respondents not using TDM, 97.5% (n = 79) would do so if all the barriers were removed. CONCLUSION: Significant barriers to TDM use were availability, cost and time lag for results. If these barriers were removed, almost all the clinicians would use TDM at least reactively and 25% would use proactively. There is an urgent need to address these barriers and optimize anti-TNF therapy for optimal outcomes.
Assuntos
Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Inquéritos e Questionários , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Análise Custo-Benefício , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Índia/epidemiologia , Doenças Inflamatórias Intestinais/economia , Infliximab/economia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Inibidores do Fator de Necrose Tumoral/economiaRESUMO
INTRODUCTION: Biologics have revolutionized the therapy of moderate-to-severe plaque psoriasis. Despite their greater efficacy over conventional systemic therapies their high cost has represented a burden for health-care systems, which limited their use. The availability of biosimilars at low cost is changing the place in therapy of biologics for psoriasis. AREAS COVERED: The role of TNF- α inhibitors in the management of plaque psoriasis, their efficacy and safety profile are presented. Phase 3 clinical trials and real-life data from the use of TNF- α inhibitor biosimilars in the treatment of plaque psoriasis are also reviewed in detail. Furthermore, arguments in favor of the use of TNF- α inhibitor biosimilars as a first-line therapy in moderate-to-severe plaque psoriasis are discussed. EXPERT OPINION: An increasing amount of data show that biosimilars represent a safe and effective alternative to the originator biologics. In the face of ever-increasing health-care costs, switching to biosimilars and starting naïve patients on the best-value biologic can reduce expenditure for patients and payers while maintaining a high-quality care. Moreover, as the cost of biosimilars is approaching the cost of conventional systemic treatments, TNF-α inhibitors biosimilars may represent a first-line systemic treatment for psoriasis patients because they are effective and safe.
Assuntos
Medicamentos Biossimilares , Psoríase , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/uso terapêutico , Humanos , Psoríase/tratamento farmacológico , Psoríase/economia , Psoríase/imunologia , Índice de Gravidade de Doença , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. METHODS: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. DISCUSSION: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. TRIAL REGISTRATION: Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).
Assuntos
Artrite Psoriásica/tratamento farmacológico , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/efeitos adversos , Adalimumab/economia , Adalimumab/uso terapêutico , Adolescente , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/psicologia , Teorema de Bayes , Estudos de Casos e Controles , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Etanercepte/efeitos adversos , Etanercepte/economia , Etanercepte/uso terapêutico , Seguimentos , Humanos , Infliximab/efeitos adversos , Infliximab/economia , Infliximab/uso terapêutico , Países Baixos/epidemiologia , Qualidade de Vida , Projetos de Pesquisa , Índice de Gravidade de Doença , Espondilartrite/psicologia , Inibidores do Fator de Necrose Tumoral/economia , Adulto JovemAssuntos
Antirreumáticos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Custos de Cuidados de Saúde/tendências , Infliximab/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Doenças Reumáticas/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antirreumáticos/economia , Medicamentos Biossimilares/economia , Humanos , Infliximab/economia , Doenças Reumáticas/economia , Inibidores do Fator de Necrose Tumoral/economia , Estados UnidosRESUMO
OBJECTIVE: To determine whether intensive combinations of conventional synthetic disease-modifying antirheumatic drugs (csDMARDS) achieve similar clinical benefits more cheaply than high-cost biologics such as tumor necrosis factor inhibitors (TNFi) in patients with active rheumatoid arthritis (RA) whose illness has failed to respond to methotrexate and another DMARD. METHODS: We used within-trial cost-effectiveness and cost-utility analyses from health and social care and 2 societal perspectives. Participants were recruited into an open-label, 12-month, pragmatic, randomized, multicenter, 2-arm, noninferiority trial in 24 rheumatology clinics in England and Wales. Costs were linked with the Health Assessment Questionnaire (HAQ; primary outcome) and quality-adjusted life years derived from 2 measures (Short-Form 36 health survey and EuroQol 5-domain 3-level instrument). RESULTS: In total, 205 participants were recruited, 104 in the csDMARD arm and 101 in the TNFi arm. Participants in the csDMARD arm with poor response at 6 months were offered TNFi; 46 participants (44%) switched. Relevant cost and outcome data were available for 93% of participants at 6-month follow-up and for 91-92% of participants at 12-month follow-up. The csDMARD arm had significantly lower total costs from all perspectives (6-month health and social care adjusted mean difference -£3,615 [95% confidence interval (95% CI) -4,104, -3,182]; 12-month health and social care adjusted mean difference -£1,930 [95% CI -2,599, -1,301]). The HAQ score showed benefit to the csDMARD arm at 12 months (-0.16 [95% CI -0.32, -0.01]); other outcomes/follow-ups showed no differences. CONCLUSION: Starting treatment with csDMARDs, rather than TNFi, achieves similar outcomes at significantly lower costs. Patients with active RA and who meet the National Institute for Health and Care Excellence criteria for expensive biologics can be treated with combinations of intensive csDMARDs in a cost-effective manner.
Assuntos
Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/economia , Idoso , Antirreumáticos/uso terapêutico , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
Tumor necrosis factor (TNF) inhibitors account for a large proportion of drugs used to treat psoriasis and are indicated first-line options in certain settings. Several biosimilar drugs based on the anti-TNF agents adalimumab, infliximab, and etanercept are now available for use in patients with psoriasis. The favorable cost differential of biosimilars is expected to improve access to biologic therapy for biologic-naive psoriasis patients, who are often undertreated. Also, substantial cost savings can be made if patients are switched to biosimilars. To date, most clinical testing of anti-TNF biosimilars approved for use in psoriasis has been performed in patients with rheumatoid arthritis, and the results extrapolated to psoriasis. Although this may initially raise concerns for clinicians looking to start their psoriasis patients on biologic treatment with a biosimilar or switch from an original biologic to a biosimilar, the process of extrapolation is tightly regulated and scientifically justified. Furthermore, available real-world evidence of the safety and efficacy of anti-TNF agents in patients with psoriasis complements clinical trial data in patients with rheumatoid arthritis. When equipped with the appropriate knowledge, clinicians should have confidence to use biosimilars for the treatment of psoriasis.
Assuntos
Medicamentos Biossimilares/uso terapêutico , Psoríase/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/provisão & distribuição , Redução de Custos , Custos de Medicamentos , Acessibilidade aos Serviços de Saúde/economia , Humanos , Estimativa de Kaplan-Meier , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/provisão & distribuiçãoRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease that requires long-term treatment to improve or maintain stable disease activity. Tumor necrosis factor inhibitors (TNFi), a class of biologic disease-modifying antirheumatic drugs (bDMARD), are effective at treating symptoms and inhibiting joint progression. Although treatment changes are not recommended in patients with stable disease, health plans have recently enacted formulary changes with higher copayments that could disrupt patient access to TNFis. OBJECTIVE: To assess the association of formulary copayment changes with real-world treatment patterns, treatment effectiveness, and health care costs among bDMARD-naive patients with RA receiving the TNFi etanercept. METHODS: This retrospective observational cohort analysis used the IBM Watson Health MarketScan Commercial Claims and Encounters Database. Adult patients with RA with 6 months of stable etanercept use (no refill gap ≥ 45 days) from January 1, 2013, through December 31, 2015, were selected and the index date was set to the first fill date after the stable-use period. Average etanercept copayment was calculated at the drug-plan level. Copayment change was defined as a monthly increase of at least $40 to account for copayment changes attributable to etanercept wholesale acquisition costs between 2014 and 2015. This amount also corresponded to the 90th percentile of average plan-level changes in etanercept copayments in the database, representing an average change in copayment by a payer. Patients were followed ≥ 12 months before and after the index date to track etanercept treatment changes and ≥ 12 months after a treatment change to track costs after etanercept copayment changes. Etanercept persistence, bDMARD switching, refill gaps, and treatment effectiveness (using a validated effectiveness algorithm) were described for patients with or without copayment change during the 12 months post-index or postchange. We also assessed the mean total of all-cause and RA-related expenditure during the 12-month post-index (or postchange) period. RESULTS: 1,970 stable patients met study inclusion criteria (mean [standard deviation] age: 50.3 [9.5] years; 77.8% female) and were evaluated. Of these, 133 (6.8%) patients had a copayment change ≥$40 during follow-up. Overall, most patients (60.3%) persisted on etanercept for the 12-month follow-up period, while 13.0% switched from etanercept, and 8.1% discontinued (refill gap of ≥ 45 days). Nearly half (48.0%) of all patients were considered effectively treated according to a validated algorithm. Compared with patients without a copayment change, those with a copayment change were more likely to switch biologics (19.5% vs. 12.6%; P = 0.021). Although statistical significance was not reached, patients with a copayment change were less likely to be persistent (54.1% vs. 60.7%; P = 0.135), and less likely to be effectively treated (42.1% vs. 48.4%; P = 0.161) than patients without a copayment change. All-cause and RA-related expenditures at baseline and post-copayment change were similar between patients with and without a copayment change. CONCLUSIONS: Changing formulary copayment of etanercept was associated with higher switching without difference in costs or health care utilization between copayment and no copayment change groups. DISCLOSURES: This study was sponsored by Amgen. Bonafede, Manjelievskaia, and Lopez-Gonzalez are employees of IBM Watson Health, which received funding from Amgen to conduct this study. Oko-osi, Collier, and Stolshek are employees and shareholders of Amgen. Gharaibeh was an employee of Amgen at the time of study execution and manuscript drafting. The authors have no other relationships that present a potential conflict of interest. Data pertaining to this study were presented in a poster at the 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, IL.
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Antirreumáticos , Artrite Reumatoide , Dedutíveis e Cosseguros , Etanercepte , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antirreumáticos/administração & dosagem , Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Estudos de Coortes , Dedutíveis e Cosseguros/economia , Etanercepte/administração & dosagem , Etanercepte/economia , Formulários Farmacêuticos como Assunto , Custos de Cuidados de Saúde , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/economiaRESUMO
PURPOSE: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept). METHODS: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation. RESULTS: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds. CONCLUSION: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.
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Medicamentos Biossimilares/economia , Medicamentos Biossimilares/uso terapêutico , Inibidores do Fator de Necrose Tumoral/economia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Redução de Custos , Dinamarca , Custos de Medicamentos , Etanercepte/economia , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/economia , Infliximab/uso terapêutico , MasculinoRESUMO
BACKGROUND: Anti-tumor necrosis factor-α (anti-TNF-α) treatments are increasingly used to treat pediatric Crohn's disease, even without a prior trial of immunomodulators, but the cost-effectiveness of such treatment algorithms has not been formally examined. Drug plan decision-makers require evidence of cost-effectiveness to inform funding decisions. The objective was to assess the incremental cost-effectiveness of early intervention with anti-TNF-α treatment vs a conventional step-up strategy per steroid-free remission-week gained from public health care and societal payer perspectives over 3 years. METHODS: A probabilistic microsimulation model was constructed for children with newly diagnosed moderate to severe Crohn's disease receiving anti-TNF-α treatment and concomitant treatments within the first 3 months of diagnosis compared with children receiving standard care consisting of steroids and/or immunomodulators with the possibility of anti-TNF-α treatment after 3 months of diagnosis. A North American multicenter observational study with 360 patients provided input into clinical outcomes and health care resource use. RESULTS: Early intervention with anti-TNF-α treatment was more costly, with an incremental cost of CAD$31,112 (95% confidence interval [CI], $2939-$91,715), and more effective, with 11.3 more weeks in steroid-free remission (95% CI, 10.6-11.6) compared with standard care, resulting in an incremental cost per steroid-free remission-week gained of CAD$2756 from an Ontario public health care perspective and CAD$2968 from a societal perspective. The incremental cost-effectiveness ratio was sensitive to the price of infliximab. CONCLUSIONS: The results suggest that although early anti-TNF-α was not cost-effective, it was clinically beneficial. These findings, along with other randomized controlled trial evidence, may inform formulary decision-making.