RESUMEN
Hereditary Angioedema (HAE) is a potentially life-threatening condition. With episodic, unpredictable swelling, HAE negatively affect the quality of life for those affected individuals. To reduce the morbidity and mortality of HAE are the primary goal for the disease management. In addition to have access to therapeutic drugs for their acute HAE attacks, many patients require long term prophylaxis (LTP) to reduce their attack frequency and severity. Preventing HAE attack by regular administration of medicine has become an important part of HAE disease management. Over the past few years, growing number of therapeutic options for the HAE LTP have made it possible for physicians to choose the most appropriate and effective treatment for individual patients. C1 INH concentrate and plasma kallikrein inhibitors (IV or SC) have largely replaced the oder modality of treatment consisting different androgen derivatives or antifibrinolytics. Additional options, such as oral kallikrein inhibitor, antisense RNA/plasma kallikrein, anti-Factor 12a, bradykinin receptor blocker or future gene therapy are under clinical investigation. The significant cost and the uncertainty of its long term safety may be the primary limiting factors for its clinical application. The limited data for young children and pregnant women pose additional challenge for physicians to assess the risk and benefit when considering LTP treatment.
Asunto(s)
Angioedemas Hereditarios/tratamiento farmacológico , Proteína Inhibidora del Complemento C1/uso terapéutico , Humanos , Prioridad del Paciente , Medicina de Precisión , Rehabilitación Psiquiátrica , Calidad de VidaRESUMEN
BACKGROUND: We conducted our first patient survey at the 2013 hereditary angioedema (HAE) patient summit and learned that, despite several novel therapies, the burden of disease was high. OBJECTIVE: To determine, from the patient's perspective, if any improvements in the current state of HAE care occurred over a two-year period between HAE patient summits. METHODS: A patient survey was conducted at the 2015 Hereditary Angioedema Association conference by using paper surveys that aimed at understanding the current state of HAE care. Questions included patient characteristics, burden of disease, and satisfaction with care and treatment options. Comparisons between patients with HAE with C1-inhibitor (HAE-C1INH) and patients with HAE with normal C1-inhibitor (HAE-nlC1INH), as well as between patients with HAE in 2013 and 2015, were performed by using χ2 tests. RESULTS: There were 232 surveys distributed, and 143 surveys were identified as complete for inclusion and analysis from patients with self-reported HAE. Most patients had type I or type II HAE (67.5% [n = 106]), with a smaller number of patients with HAE-nlC1INH (23.6% [n = 37]). In 2015, almost half of the patients with HAE-C1INH (47.1%) and 56.7% of the patients with HAE-nlC1INH experienced a delay of ≥10 years between initial symptoms and diagnosis. Among the patients with HAE-C1INH, 25% reported one or more attacks per week and another 48% reported experiencing one or more attacks per month (fewer than one attack per week). The patients with HAE-nlC1INH reported attacks more frequently than did the patients with HAE-C1INH (p = 0.002), with 59.5% who reported attacks at least once a week. Emergency care was reported one or more times per month in 5% of the patients with HAE-C1INH and in 24.3% of the patients with HAE-nlC1INH. CONCLUSION: Similar to 2013, although significant progress has been made, there is still a high burden of disease that faces patients with HAE.
Asunto(s)
Angioedemas Hereditarios/epidemiología , Costo de Enfermedad , Pacientes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Diagnóstico Tardío , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Calidad de la Atención de Salud , Encuestas y Cuestionarios , Estados Unidos/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: For prophylaxis of hereditary angioedema (HAE) attacks, replacement therapy with human C1-inhibitor (C1-INH) treatment is approved and available as intravenous [C1-INH(IV)] (Cinryze®) and subcutaneous [C1-INH(SC)] HAEGARDA® preparations. In the absence of a head-to-head comparative study of the two treatment modalities, an indirect comparison of data from 2 independent but similar clinical trials was undertaken. METHODS: Two similar randomized, double-blind, placebo-controlled, crossover studies were identified which evaluated either C1-INH(SC) (COMPACT; NCT01912456; 16 weeks) or C1-INH(IV) (CHANGE; NCT01005888; 14 weeks) vs. placebo (on-demand treatment only) for routine prevention of HAE attacks. Individual patient data from each trial were used to conduct an indirect comparison of treatment effects. Attack reductions (absolute and percent of mean/median number of monthly HAE attacks reduction over placebo) were compared between the two C1-INH formulations at approved/recommended doses: C1-INH(SC) 60 IU/kg twice weekly (n = 45) and 1000 U of C1-INH(IV) twice weekly (n = 22). Point estimates were adjusted using mixed and quantile regression models that controlled for study design. RESULTS: The absolute mean monthly numbers of HAE attack reductions were 3.6 (95% CI 2.9, 4.2) for C1-INH(SC) 60 IU/kg vs. placebo and 2.3 (1.4, 3.3) for C1-INH(IV) vs. placebo; between-product difference, 1.3 (0.1, 2.4; P = 0.034). The mean percent reduction in monthly attack rate was significantly greater with C1-INH(SC) as compared with C1-INH(IV) (84% vs. 51%; P < 0.001). The percentages of subjects experiencing ≥ 50%, ≥ 70%, and ≥ 90% reductions in monthly HAE attack rates versus placebo were significantly higher with C1-INH(SC) 60 IU/kg as compared to C1-INH(IV) 1000 U (≥ 50% reduction: 91% vs. 50%, odds ratio [OR] = 10.33, P = 0.003; ≥ 70% reduction: 84% vs. 46%, OR = 6.19, P = 0.005; ≥ 90% reduction: 57% vs. 18%, OR = 6.04, P = 0.007). CONCLUSION: Within the limitations of an indirect study comparison, this analysis suggests greater attack reduction with twice-weekly C1-INH(SC) 60 IU/kg as compared to twice-weekly C1-INH(IV) 1000 U for the routine prevention of HAE attacks.
RESUMEN
BACKGROUND: Hereditary angioedema (HAE) is a life-threatening disorder characterized by recurrent angioedema. Icatibant, a subcutaneous bradykinin-B2-receptor antagonist, is an effective on-demand therapy. Data outside the United States suggest that self-administration is tolerated and patient-preferred compared with administration by health care professionals at medical facilities (HCP-administration). OBJECTIVE: A prospective, multicenter study was conducted in the United States to compare icatibant self-administration and HCP-administration. METHODS: Subjects 18 years or older with type I or II HAE were recruited. The first 2 HAE attacks after enrollment were treated at medical facilities. Subjects were instructed by a health care professional on self-administration during icatibant treatment for the second HAE attack. Icatibant was self-administered for all subsequent attacks. For each treated HAE attack, efficacy, safety, and tolerability data were recorded. RESULTS: Nineteen patients with HAE received icatibant for 79 distinct HAE attacks. Mean attack duration was significantly shorter with self-administration (n = 50; 547 ± 510 minutes) than with HCP-administration (n = 29; 968 ± 717 minutes; P = .006). Mean time to treatment was significantly shorter with self-administration (143 ± 226 minutes) than with HCP-administration (361 ± 503 minutes; P < .0001). Shorter times to treatment were associated with shorter time from treatment to symptom resolution (r = 0.35; P = .02). Improvements in visual analog scale score and patient symptom score from pretreatment to 4 hours postinjection were comparable between self-administration and HCP-administration. There were no serious adverse events or discontinuations due to adverse events with self-administration or HCP-administration. CONCLUSIONS: Icatibant self-administration shortened attack duration and time to treatment, with no difference in safety or local tolerability compared with HCP-administration. These findings support icatibant as an effective on-demand option for home-based treatment.
Asunto(s)
Angioedemas Hereditarios/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Antagonistas del Receptor de Bradiquinina B2/uso terapéutico , Bradiquinina/análogos & derivados , Servicios de Atención de Salud a Domicilio , Adulto , Anciano , Anciano de 80 o más Años , Angioedemas Hereditarios/epidemiología , Antiinflamatorios no Esteroideos/administración & dosificación , Bradiquinina/administración & dosificación , Bradiquinina/uso terapéutico , Antagonistas del Receptor de Bradiquinina B2/administración & dosificación , Personal de Salud , Humanos , Inyecciones Subcutáneas , Persona de Mediana Edad , Prioridad del Paciente , Estudios Prospectivos , Autoadministración , Tiempo de Tratamiento/estadística & datos numéricos , Resultado del Tratamiento , Estados Unidos/epidemiología , Escala Visual Analógica , Adulto JovenRESUMEN
Hereditary angioedema (HAE) is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH). The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze(®), Berinert(®), and Cetor(®); however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver) is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE.