RESUMO
European real-world data indicate that front-line treatment with caplacizumab is associated with improved clinical outcomes compared with delayed caplacizumab treatment. The objective of the study was to describe the characteristics, treatment patterns, and outcomes in hospitalized patients with an immune-mediated thrombotic thrombocytopenic purpura (iTTP) episode treated with front-line versus delayed caplacizumab in the US. This retrospective cohort analysis of a US hospital database included adult patients (≥18 years) with an acute iTTP episode (a diagnosis of thrombotic microangiopathy and ≥1 therapeutic plasma exchange [TPE] procedure) from January 21, 2019, to February 28, 2021. Unadjusted baseline characteristics, treatment patterns, healthcare resource utilization, and costs were compared between patients who received front-line versus delayed (<2 vs ≥2 days after TPE initiation) caplacizumab treatment. Out of 39 patients, 16 (41.0%) received front-line and 23 (59.0%) received delayed treatment with caplacizumab. Baseline characteristics and symptoms were similar between the two groups. Patients who received front-line caplacizumab treatment had significantly fewer TPE administrations (median: 5.0 vs 12.0); and a significantly shorter hospital stay (median: 9.0 days vs 16.0 days) than patients receiving delayed caplacizumab therapy. Both of these were significantly lower in comparison of means (t-test P < .01). Median inpatient costs (inclusive of caplacizumab costs) were 54% higher in the delayed treated patients than in the front-line treated patients (median: $112â 711 vs $73â 318). TPE-specific cost was lower in the front-line treated cohort (median: $6 989 vs $10â 917). In conclusion, front-line treatment with caplacizumab had shorter hospitalizations, lower healthcare resource utilization, and lower costs than delayed caplacizumab treatment after TPE therapy.
Assuntos
Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Trombose , Adulto , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Estudos Retrospectivos , Anticorpos de Domínio Único/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Troca Plasmática , Trombose/tratamento farmacológico , Proteína ADAMTS13 , HospitaisRESUMO
Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.
Assuntos
Fibrinolíticos/economia , Modelos Econômicos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Anticorpos de Domínio Único/economia , Adolescente , Adulto , Idoso , Ensaios Clínicos Fase II como Assunto/economia , Ensaios Clínicos Fase III como Assunto/economia , Terapia Combinada , Análise Custo-Benefício , Árvores de Decisões , Custos de Medicamentos , Quimioterapia Combinada/economia , Feminino , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/economia , Humanos , Imunossupressores/economia , Imunossupressores/uso terapêutico , Tempo de Internação/economia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/economia , Troca Plasmática/economia , Púrpura Trombocitopênica Trombótica/economia , Púrpura Trombocitopênica Trombótica/terapia , Recidiva , Rituximab/economia , Rituximab/uso terapêutico , Anticorpos de Domínio Único/efeitos adversos , Anticorpos de Domínio Único/uso terapêutico , Padrão de Cuidado/economia , Estados Unidos , Adulto JovemRESUMO
The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.
Assuntos
Corticosteroides/uso terapêutico , Troca Plasmática , Púrpura Trombocitopênica Trombótica/terapia , Rituximab/uso terapêutico , Anticorpos de Domínio Único/uso terapêutico , Proteína ADAMTS13/sangue , Adulto , Terapia Combinada , Ensaios de Uso Compassivo , Progressão da Doença , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Estudo Historicamente Controlado , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/mortalidade , Índice de Gravidade de Doença , Anticorpos de Domínio Único/efeitos adversos , Anticorpos de Domínio Único/economia , Tromboembolia/etiologia , Resultado do Tratamento , Fator de von Willebrand/antagonistas & inibidoresRESUMO
Acquired thrombotic thrombocytopenic purpura is a rare blood disorder with a high early mortality rate, if untreated. Standard of care plasma exchange and glucocorticoids have dramatically improved survival. However, additional advancements are necessary to further decrease mortality. Caplacizumab-yhdp (Cablivi®) is the first Food and Drug Administration-approved treatment indicated for adult patients with acquired thrombotic thrombocytopenic purpura, in combination with plasma exchange and immunosuppressive therapy. However, there are considerable risks associated with the use of caplacizumab and they must be weighed against the benefits of the medication.