RESUMO
Aim: Novel treatment options for relapsed/refractory diffuse large B-cell lymphoma include T-cell targeting therapies. Practice efficiency and cost are important for informed treatment decisions.Materials/methods: An institutional decision-maker cost model was developed for 6-month, 1-year and median cycles of treatment time horizons comparing practice efficiency and costs of epcoritamab vs glofitamab and axicabtagene ciloleucel (axi-cel).Results: Overall, epcoritamab required the shortest personnel and chair time, except over 1 year (second shortest chair time). Across all time horizons, epcoritamab was cost-saving vs axi-cel and had similar costs to glofitamab on a per-month basis.Conclusion: Epcoritamab reduced personnel and chair time. Additionally, epcoritamab was cost-saving vs axi-cel and had similar costs to glofitamab on a per-month basis.
There are new ways to treat diffuse large B-cell lymphoma, which is a type of cancer called lymphoma. When new treatments are available it is important to see if they take more or less time to give to patients and how much they cost versus other treatments. This study looked at three drugs used to treat diffuse large B-cell lymphoma, including epcoritamab, axi-cel and glofitamab. It estimated the time and cost with those treatments in patients who get them for 6 months, 1 year or for the most common length of time in the clinical trials. In most of the scenarios, epcoritamab had the least time needed for nurses or doctors and the least time needed for a patient to be in a chair in a clinic. When thinking about the cost per month, epcoritamab saved money versus axi-cel and was similar to glofitamab.
Assuntos
Anticorpos Biespecíficos , Análise Custo-Benefício , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/economia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Imunoterapia Adotiva/economia , Imunoterapia Adotiva/métodos , Anticorpos Biespecíficos/economia , Anticorpos Biespecíficos/uso terapêutico , Receptores de Antígenos Quiméricos , Recidiva Local de Neoplasia/terapia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/economia , Custos de Cuidados de Saúde/estatística & dados numéricosRESUMO
Introduction: Novel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective. Methods: A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients. Results: The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. Discussion: This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.
Assuntos
Produtos Biológicos , Análise Custo-Benefício , Linfoma Folicular , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/economia , Linfoma Folicular/mortalidade , Estados Unidos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/economia , Masculino , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/economia , Feminino , Imunoterapia Adotiva/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Pessoa de Meia-Idade , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/economia , Adulto , Anos de Vida Ajustados por Qualidade de Vida , Recidiva Local de Neoplasia/tratamento farmacológico , IdosoRESUMO
Current treatment strategies for multiple myeloma (MM) are highly effective, but most patients develop relapsed/refractory disease (RRMM). The anti-CD38/CD3xCD28 trispecific antibody SAR442257 targets CD38 and CD28 on MM cells and co-stimulates CD3 and CD28 on T cells (TCs). We evaluated different key aspects such as MM cells and T cells avidity interaction, tumor killing, and biomarkers for drug potency in three distinct cohorts of RRMM patients. We found that a significantly higher proportion of RRMM patients (86%) exhibited aberrant co-expression of CD28 compared to newly diagnosed MM (NDMM) patients (19%). Furthermore, SAR442257 mediated significantly higher TC activation, resulting in enhanced MM killing compared to bispecific functional knockout controls for all relapse cohorts (Pearson's r = 0.7). Finally, patients refractory to anti-CD38 therapy had higher levels of TGF-ß (up to 20-fold) compared to other cohorts. This can limit the activity of SAR442257. Vactoserib, a TGF-ß inhibitor, was able to mitigate this effect and restore sensitivity to SAR442257 in these experiments. In conclusion, SAR442257 has high potential for enhancing TC cytotoxicity by co-targeting CD38 and CD28 on MM and CD3/CD28 on T cells.
Assuntos
ADP-Ribosil Ciclase 1 , Anticorpos Biespecíficos , Mieloma Múltiplo , Linfócitos T , Humanos , ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Linhagem Celular Tumoral , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Mieloma Múltiplo/imunologia , Recidiva , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/efeitos dos fármacosRESUMO
BACKGROUND: Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1; NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab. METHODS: Patients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing. RESULTS: Baseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here. CONCLUSIONS: This biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.
Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Linfoma Difuso de Grandes Células B , Humanos , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Resultado do Tratamento , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Antígenos CD20RESUMO
BACKGROUND: We investigate the geographical and racial disparities in accessing CAR-T and bispecific antibodies trials for DLBCL. MATERIALS AND METHODS: ClinicalTrials.gov was searched, and 75 trials with at least 1 open site in the US were included. 2020 US Census Bureau data was used to obtain data on race and ethnicity. SPSS version 26 was used for analysis. RESULTS: There were 62 CAR-T and 13 bispecific antibodies trials with 6221 enrolled or expected to enroll patients. Eighty-five percent of the clinical trials were only open in the US, and the majority 64% were pharmaceutical-funded. There were 126 unique study sites distributed over 31 states with 11 (0-51) mean number of trials per state and 4.5 (1-26) and 4.4 (1-24) mean number of CAR-T and bispecific antibodies trials per site, respectively. Southern states had the most number of trials 31%, followed by Midwestern 25%, Northeastern 24%, and Western 20%. The highest number of study locations were in California 13, New York 9, and Pennsylvania 9, while the highest number of open studies were in California 51, Texas 32, and New York 23. Twenty states had no open CAR-T or bispecific antibodies trials. Only 33% of African Americans (AA) lived in a county with a trial, and 7 out of 10 states with the highest proportion of AA residents (18.6%-41.4%) have no or less than 4 trial sites. Of the 62 counties analyzed, 92% were White predominant, while only 8% were AA predominant (P = .009). CONCLUSIONS: Strategies should be framed to address the observed disparities and to improve access.
Assuntos
Anticorpos Biespecíficos , Linfoma Difuso de Grandes Células B , Humanos , Anticorpos Biespecíficos/uso terapêutico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/imunologia , Ensaios Clínicos como Assunto , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estados Unidos , Imunoterapia Adotiva/métodos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricosRESUMO
INTRODUCTION: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). AIM: This study assessed the economic evaluation of emicizumab treatment for non-inhibitor severe haemophilia A (HA) patients in India. METHODS: A Markov model evaluated the cost-effectiveness of emicizumab prophylaxis compared to on-demand therapy (ODT), low-dose prophylaxis (LDP; 1565 IU/kg/year), intermediate-dose prophylaxis (IDP; 3915 IU/kg/year) and high-dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors. Inputs from HAVEN-1 and HAVEN-3 trials included transition probabilities of different bleeding types. Costs and benefits were discounted at a 3.5% annual rate. RESULTS: In the base-case analysis, emicizumab was cost-effective compared to HDP, with an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years (QALY) of Indian rupees (INR) 27,869. Compared to IDP, ODT and LDP, emicizumab prophylaxis could be considered a cost-effective option if the paying threshold is >1 per capita gross domestic product (GDP) with ICER/QALY values of INR 264,592, INR 255,876 and INR 305,398, respectively. One-way sensitivity analysis (OWSA) highlighted emicizumab cost as the parameter with the greatest impact on ICERs. Probabilistic sensitivity analysis (PSA) indicated that emicizumab had a 94.7% and 49.4% probability of being cost-effective at willingness-to-pay (WTP) thresholds of three and two-times per capita GDP. CONCLUSION: Emicizumab prophylaxis is cost-effective compared to HDP and provides value for money compared to ODT, IDP, and LDP for severe non-inhibitor PwHA in India. Its long-term humanistic, clinical and economic benefits outweigh alternative options, making it a valuable choice in resource-constrained settings.
Assuntos
Anticorpos Biespecíficos , Hemofilia A , Humanos , Hemofilia A/tratamento farmacológico , Análise de Custo-Efetividade , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Análise Custo-Benefício , Fator VIII/uso terapêuticoRESUMO
Oncolytic virotherapy is an emerging and safe therapeutic approach based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus armed with Bispecific Antibody (BsAb) molecules targeting PD-L1/CD3 (oHSV2-PD-L1/CD3-BsAb) to treat human malignancies. We demonstrated the anti-tumor efficacy of oHSV2-PD-L1/CD3-BsAb. To move forward with clinical trials of oHSV2-PD-L1/CD3-BsAb, we conducted a comprehensive preclinical safety evaluation, including hemolysis test, anaphylaxis test, repeated dose toxicity test in cynomolgus monkeys, biodistribution in cynomolgus monkeys and tissue cross-reactivity of PD-L1/CD3-BsAb with human and cynomolgus monkey tissues in vitro. Our preclinical safety evaluation indicated that oHSV2-PD-L1/CD3-BsAb is safe and suitable for clinical trials. After undergoing a thorough evaluation by the United States Food and Drug Administration (FDA), oHSV2-PD-L1/CD3-BsAb has successfully obtained approval to initiate Phase I clinical trials in the United States (FDA IND: 28717).
Assuntos
Anticorpos Biespecíficos , Neoplasias , Terapia Viral Oncolítica , Animais , Humanos , Herpesvirus Humano 2 , Macaca fascicularis , Distribuição Tecidual , Antígeno B7-H1 , Anticorpos Biespecíficos/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
Prophylactic emicizumab is cost-ineffective in adults with moderate or mild hemophilia A without inhibitors at current pricing. The price of prophylactic emicizumab would need to decrease by >35% to become cost-effective in this patient population.
Assuntos
Anticorpos Biespecíficos , Hemofilia A , Adulto , Humanos , Estados Unidos , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Análise Custo-Benefício , Hemorragia/prevenção & controle , Anticorpos Biespecíficos/uso terapêuticoRESUMO
INTRODUCTION: EHL FVIII products and emicizumab provide clinicians with other prophylactic options for treating hemophilia A, however, it is unclear if emicizumab is a cost-saving option. The objective of this study is to estimate the health and economic effects of using prophylactic EHL FVIII, SHL FVIII, and emicizumab in severe haemophilia A patients. MATERIALS AND METHODS: A state-transition Markov model evaluated the cost-effectiveness of prophylactic SHL FVIII, EHL FVIII, and emicizumab in a cohort of 2-year-old male patients over a lifetime horizon in the form of a cost-utility analysis using a Canadian provincial ministry of health payer perspective. The transition probabilities, costs, and utilities were obtained from literature and the Canadian Bleeding Disorders Registry. Probabilistic sensitivity and scenario analyses were performed to test the robustness of the model. RESULTS: The base-case analysis, over a lifetime horizon, resulted in a total cost and utilities per person for SHL FVIII, EHL FVIII, and emicizumab of $27.2 million (M), $36.7 M, and $26.2 M, respectively, and 31.30, 31.16, and 31.61 quality-adjusted life years, respectively. Emicizumab treatment resulted in 29 and 16 less bleeds in a lifetime compared to SHL FVIII and EHL FVIII, respectively. Probabilistic sensitivity analysis showed that emicizumab was cost-saving 100% of the time compared to SHL FVIII and EHL FVIII. CONCLUSION: The cost-utility analysis showed that emicizumab is more effective and may be less costly than FVIII for Canadian haemophilia A patients, conditional on drug cost assumptions. Our model indicates that emicizumab may be a potentially favourable treatment option for minimising healthcare costs and providing higher effectiveness.
Assuntos
Anticorpos Biespecíficos , Hemofilia A , Masculino , Humanos , Pré-Escolar , Hemofilia A/tratamento farmacológico , Análise Custo-Benefício , Canadá , Anticorpos Biespecíficos/uso terapêutico , Hemorragia/prevenção & controle , Fator VIII/uso terapêutico , Fator VIII/farmacologiaRESUMO
Since March 2019, émicizumab is indicated for the treatment of patients with severe haemophilia A without inhibitor. This therapy's price amounts approximately to 33 600 per 4 weeks for a 70kg patient which represents about two times more than a factor VIII concentrates treatment's price. This study aims to assess the budgetary impact for the French Health Insurance of an émicizumab therapy introduction for patients with severe haemophilia A without inhibitor. It was an observational, retrospective, and monocentric study. Every severe haemophilia A without inhibitor patient over 18 years old followed at the Cochin Hospital haemophilia treatment centre who received émicizumab from June 2020 and for at least one year have been included. The budgetary impact was estimated by comparing the total costs of patient care the year before versus the year after émicizumab initiation. Total costs of patient care included prices of i) treatments consumed, ii) consultations with specialist physicians, iii) hospitalizations and iv) imaging procedures. Thirty-eight patients were included. The total cost of patient care increased significantly the year after émicizumab introduction (P < 0.0001). On average, this cost was estimated at 537 887 ± 137 139 per patient whereas it was at 151 442 ± 94 708 the year before. While costs of physician consultations increased, no significant difference has been reported about hospitalizations and imaging costs. Over a one-year period, émicizumab therapy significantly increased the total costs of patient care. It is mostly caused by the drug price itself.
Assuntos
Anticorpos Biespecíficos , Hemofilia A , Adolescente , Humanos , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemofilia A/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: A cost-minimization model was developed to compare recombinant factor VIII Fc (rFVIIIFc) and emicizumab as prophylaxis for hemophilia A without inhibitors. METHODS: The model was based on 100 patients from the healthcare payer perspective in the UK, France, Italy, Spain, and Germany (5-year time horizon). Costs included: drug acquisition; emicizumab wastage by bodyweight (manufacturer's dosing recommendations); and additional FVIII for breakthrough bleeds. Scenario analyses (UK only): reduced emicizumab dosing frequency; and emicizumab maximum wastage. RESULTS: Total incremental 5-year savings for rFVIIIFc rather than emicizumab use range from 89,320,131 to 149,990,408 in adolescents/adults (≥12 years) and 173,417,486 to 253,240,465 in children (<12 years). Emicizumab wastage accounts for 6% of its total cost in adolescents/adults and 26% in children. Reducing the emicizumab dosing frequency reduces the incremental cost savings with rFVIIIFc, but these remain substantial (adolescents/adults, >92 million; children >32 million). Maximum emicizumab wastage increases by 86% and 106%, respectively, increasing the incremental cost savings with rFVIIIFc to 125,352,125 and 105,872,727, respectively. CONCLUSION: Based on cost-minimization modeling, rFVIIIFc use for hemophilia A prophylaxis in patients without inhibitors is associated with substantial cost savings in Europe, reflecting not only higher acquisition costs of emicizumab, but also other costs including wastage related to available vial sizes.
Assuntos
Anticorpos Biespecíficos , Anticorpos Monoclonais Humanizados , Fator VIII , Hemofilia A , Adolescente , Adulto , Anticorpos Biespecíficos/economia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Custos e Análise de Custo , Europa (Continente) , Fator VIII/economia , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , HumanosRESUMO
INTRODUÇÃO: A leucemia linfoblástica aguda (LLA) pediátrica é uma neoplasia maligna agressiva e heterogênea caracterizada pela proliferação clonal e acúmulo de linfoblastos na medula óssea e sangue periférico. Entre os pacientes pediátricos, mais de 95% atingem remissão completa após o primeiro tratamento e 75% a 85% permanecem livre de doença por cinco anos após o diagnóstico. Porcentagens de 15% a 20% sofrem recidiva que são classificadas em risco padrão (RP) ou alto risco (AR). Em crianças com primeira recidiva medular de alto risco a sobrevida global é de 20%. A recidiva após o tratamento inicial é a segunda maior causa de mortalidade relacionada ao câncer em crianças. Crianças que apresentam recidiva de alto risco ao tratamento inicial são candidatas ao transplante de células hematopoiéticas após atingirem uma segunda remissão completa, entretanto, as chances de remissão diminuem significativamente entre a primeira, segunda e terceiras recidivas. Nessa população, a presença de doença residual
Assuntos
Humanos , Pré-Escolar , Criança , Leucemia Aguda Bifenotípica/tratamento farmacológico , Anticorpos Biespecíficos/uso terapêutico , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economiaRESUMO
With increasing numbers of bispecific antibodies (BsAbs) and multispecific products entering the clinic, recent data highlight immunogenicity as an emerging challenge in the development of such novel biologics. This review focuses on the immunogenicity risk assessment (IgRA) of BsAb-based immunotherapies for cancer, highlighting several risk factors that need to be considered. These include the novel scaffolds consisting of bioengineered sequences, the potentially synergistic immunomodulating mechanisms of action (MOAs) from different domains of the BsAb, as well as several other product-related and patient-related factors. In addition, the clinical relevance of anti-drug antibodies (ADAs) against selected BsAbs developed as anticancer agents is reviewed and the advances in our knowledge of tools and strategies for immunogenicity prediction, monitoring, and mitigation are discussed. It is critical to implement a drug-specific IgRA during the early development stage to guide ADA monitoring and risk management strategies. This IgRA may include a combination of several assessment tools to identify drug-specific risks as well as a proactive risk mitigation approach for candidate or format selection during the preclinical stage. The IgRA is an on-going process throughout clinical development. IgRA during the clinical stage may bridge the gap between preclinical immunogenicity prediction and clinical immunogenicity, and retrospectively guide optimization efforts for next-generation BsAbs. This iterative process throughout development may improve the reliability of the IgRA and enable the implementation of effective risk mitigation strategies, laying the foundation for improved clinical success.
Assuntos
Anticorpos Biespecíficos , Anticorpos Biespecíficos/uso terapêutico , Humanos , Fatores Imunológicos , Imunoterapia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
INTRODUCTION: Subcutaneous emicizumab prophylaxis substantially reduces bleeding episodes in patients with haemophilia A (PwHA) and factor VIII inhibitor. However, thrombotic events occurred in some PwHA with inhibitor who had received high cumulative doses of activated prothrombin complex concentrates at their breakthrough bleeds, when they were also given prophylactic emicizumab. After that, although the recommended guidance was proposed for bypassing agents (BPAs) therapy under emicizumab prophylaxis for haemostatic management, detailed investigation(s) is(are) required to elucidate the safe and appropriate dose of BPAs to use concomitantly with emicizumab prophylaxis. METHODS AND ANALYSIS: In the UNEBI Study, 60 PwHA with inhibitor will be enrolled for a maximum duration of 3 years, and samples of 20 events following concomitant use of BPAs with emicizumab will be collected. An 'event' is defined as obtaining blood samples before and after administration of BPA when a breakthrough bleed or a surgical procedure occurs. The coagulation potential in the obtained samples will be measured by global coagulation assays. The primary endpoint is the degree of improvement in the maximum coagulation rate by clot waveform analysis (CWA) before and after administration of fixed-dose BPAs. This parameter obtained from CWA, which is triggered with an optimally diluted mixture of prothrombin time/activated partial thromboplastin time-reagents, is reported to be an excellent marker for assessing the degree of improvement in coagulation potential in emicizumab-treated plasma. ETHICS AND DISSEMINATION: The UNEBI Study was approved by the Japan Certified Review Board of Nara Medical University. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: jRCTs051190119.
Assuntos
Anticorpos Biespecíficos , Hemofilia A , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemorragia/complicações , HumanosRESUMO
Since 2019, severe haemophilia A without inhibitors can be treated with emicizumab. Its action, route of administration and management justified the creation of new tools for therapeutic education sessions addressed to patients. The main objective of our work was to assess the knowledge and skills acquired by patients after therapeutic education. The various documents created were a video, a slideshow, clinical cases in form of cards, and summary sheets intended for patients. At treatment beginning, a pharmaceutical consultation was proposed to all patients. Two months later, an evaluation was carried out and a second pharmaceutical consultation aimed to consolidate the achievements of patients. Simultaneously, a clinical self-evaluation by the patients was carried out. Thirty-six patients were included in the study. Theoretical items: method of manufacture, mechanism of action and regimen, are known for more than ¾ of patients. Practical skills, such as administration modalities, management of missed doses or bleeding, are familiar for more than 8 out of 10 patients. Sixteen (44.4%) patients presented an up-to-date haemophilia card. The assessment of the knowledge and skills of patients is encouraging since most of the items are acquired. These result highlights the interest of the new tools developed for the therapeutic education sessions.