RESUMO
INTRODUCTION: The exact risk of developing a thromboembolic event (TEE) while using complement 1 esterase inhibitors (C1-INHs) is currently undetermined for patients with hereditary angioedema (HAE). This systematic review aimed to define the potential risk of TEEs from these agents. AREAS COVERED: This evaluation covers publications examining or mentioning the risk of TEEs in association with C1-INHs. A systematic literature search was conducted utilizing PubMed, Scopus, and ProQuest. This review utilized search results through January 2020 and followed the PRISMA recommendations for a systematic review. Articles not available in English and animal or in-vitro studies were excluded. For inclusion, studies had to be open-label, randomized-controlled, cross-sectional, or clinical observational studies. A total of 13 studies met inclusion criteria and yielded 1716 patients receiving at least one dose of C1-INH, though only 41 incidences of thrombosis were documented. EXPERT OPINION: Significant heterogeneity exists in the available literature concerning both study design and the reporting of data; therefore, interpretation of thrombotic risk is difficult. TEEs are rarely reported in the literature, and they seem unlikely to occur in patients without underlying risk factors. Important risk factors include those found in the prescribing information of C1-INHs.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1/efeitos adversos , Tromboembolia/induzido quimicamente , Proteínas Inativadoras do Complemento 1/administração & dosagem , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tromboembolia/tratamento farmacológico , Trombose/induzido quimicamenteRESUMO
BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert®/CSL Behring) in patients of any age, including many older adults. METHODS: This observational registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered prospective (post-enrollment) and retrospective (pre-enrollment) usage and adverse event (AE) data on subjects treated with pnfC1-INH. RESULTS: The registry documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE attacks treated with pnfC1-INH administration were reported among 25 of the 27 (92.6 %) older adults. Among the older adults, mean (standard deviation [SD]) (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH doses were lower than those reported for 252 'younger adults' (those aged <65 years: 12.9 [6.2], 12.5 IU/kg, respectively). A total of 19 AEs occurred in 8 of 23 (34.8 %) older adults with prospective data, for rates of 0.83 events per subject and 0.02 events per infusion, similar to corresponding rates in younger adults (0.91 and 0.03, respectively). None of the AEs were considered related to pnfC1-INH, and all but two events (prostatectomy, gastrointestinal bleeding) were mild or moderate in severity. Administration of pnfC1-INH outside of a healthcare setting was reported for 1609 infusions in 16 older adults, representing 94.6 % of all pnfC1-INH infusions in this age group. There were no recorded instances of difficulty with self-administration of intravenous pnfC1-INH. CONCLUSIONS: These findings suggest a high degree of safety with intravenous pnfC1-INH use in older adults with HAE, regardless of administration setting. Trial Registration Clinicaltrials.gov NCT01108848.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1 , Sistema de Registros , Adulto , Idoso , Angioedemas Hereditários/metabolismo , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Inativadoras do Complemento 1/efeitos adversos , Proteínas Inativadoras do Complemento 1/uso terapêutico , Proteína Inibidora do Complemento C1 , Europa (Continente) , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Estados UnidosAssuntos
Proteína Inibidora do Complemento C1/análise , Sepse/sangue , Adulto , Idoso , Ativação do Complemento , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Inativadoras do Complemento 1/fisiologia , Inibidores de Cisteína Proteinase/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sepse/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Hereditary angio-oedema (HAE), C1 inhibitor HAE (C1-INH-HAE) type I and C1-INH-HAE type II, are inherited disorders characterised by potentially life-threatening recurrent swellings, caused by a deficiency of C1 inhibitor. Management includes attack treatment or prevention using prophylaxis/routine prevention. AIM: To evaluate the success of self-administration training as part of a home care programme for treatment of HAE using intravenous C1 inhibitor. METHODS: In total, 18 patients (7 men, 11 women; aged 18-72 years) were trained to self-administer a plasma-derived C1 inhibitor concentrate for acute treatment or routine prevention of HAE attacks. The number of training sessions needed to learn intravenous self-administration, delay in time to treatment and reduction in attack frequency (per month) were evaluated after completion of the training. RESULTS: All patients successfully completed training. The median number of training sessions required to be capable of unassisted/independent self-injection was 5 (range 2-30). Time to treatment was reduced from a median of 4.5 h (270 min) by medical professionals to 15 min by patients after self-administration training). Using the treatment as routine prevention resulted in a reduction of median frequency of attacks from 8 to 0.5 attacks/month. CONCLUSION: C1 inhibitor self-administration for the treatment of HAE allows patients to quickly treat attacks at home, potentially reducing attack severity. The results also demonstrate the benefit of self-administered routine prevention therapy in a real-world patient population. Self-administered therapy potentially allows patients to gain greater control over their attacks, resulting in a reduction in healthcare utilization.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1/administração & dosagem , Educação de Pacientes como Assunto/métodos , Tempo para o Tratamento , Proteínas Inativadoras do Complemento 1/uso terapêutico , Proteína Inibidora do Complemento C1 , Edema , Infusões Intravenosas/métodos , AutoadministraçãoAssuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1/administração & dosagem , Angioedemas Hereditários/genética , Cuidadores , Proteínas Inativadoras do Complemento 1/biossíntese , Proteínas Inativadoras do Complemento 1/genética , Proteína Inibidora do Complemento C1 , Feminino , Serviços de Assistência Domiciliar , Humanos , Lactente , Injeções Subcutâneas , Mutação/genéticaRESUMO
BACKGROUND: Hereditary angioedema (HAE) caused by a deficiency in functional C1 esterase inhibitor (C1INH) is characterized by recurrent episodes of cutaneous and/or mucosal/submucosal tissue swelling affecting multiple anatomic locations. Previous studies demonstrated efficacy of recombinant human C1INH (rhC1INH) for acute HAE attacks. OBJECTIVE: This study evaluated the efficacy and safety of rhC1INH (50 IU/kg) for the treatment of multiple HAE attacks in an open-label extension study. METHODS: Time to onset of symptom relief and time to minimal symptoms were assessed using a Treatment Effect Questionnaire (TEQ), a visual analog scale, and a 6-point ordinal scale Investigator Score. RESULTS: Forty-four patients received rhC1INH, and a single dose was administered for 215 of 224 (96%) attacks. Median time to beginning of symptom relief based on TEQ for the first 5 attacks was 75.0 (95% CI, 69-89) minutes, ranging from 62.5 (95% CI, 48-90) to 134.0 (95% CI, 32-119) minutes. Median time to minimal symptoms using TEQ for the first 3 attacks was 303.0 (95% CI, 211-367) minutes. rhC1INH was well tolerated. There were no discontinuations due to adverse events. No thrombotic or anaphylactic events were reported, and repeat rhC1INH treatments were not associated with neutralizing anti-C1INH antibodies. CONCLUSIONS: A single 50-IU/kg dose rhC1INH was effective for improving symptoms of an HAE attack with sustained efficacy for treatment of subsequent attacks. rhC1INH had a positive safety profile throughout the study. This study supports repeated use of rhC1INH over time in patients with HAE attacks.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1/uso terapêutico , Adulto , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/imunologia , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Inativadoras do Complemento 1/efeitos adversos , Proteína Inibidora do Complemento C1 , Esquema de Medicação , Europa (Continente) , Feminino , Humanos , Injeções Intravenosas , Israel , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Estados UnidosAssuntos
Angioedemas Hereditários/psicologia , Qualidade de Vida , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/genética , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteína Inibidora do Complemento C1 , Dinamarca/epidemiologia , Humanos , Fatores Imunológicos/administração & dosagem , Injeções Intravenosas , Autoadministração , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoAssuntos
Angioedemas Hereditários/prevenção & controle , Angioedemas Hereditários/terapia , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Adulto , Angioedemas Hereditários/complicações , Angioedemas Hereditários/etiologia , Bradicinina/metabolismo , Permeabilidade Capilar/genética , Pré-Escolar , Ativação do Complemento/genética , Proteínas Inativadoras do Complemento 1/genética , Proteína Inibidora do Complemento C1 , Danazol/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Plasma/metabolismo , Guias de Prática Clínica como Assunto , Proteínas Recombinantes/genética , Adulto JovemRESUMO
Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality of life. Most studies have been conducted in adults. We report a 13-year-old boy who quickly learned self-administration, which resulted in reduced frequency and severity of attacks. The aim of this report is to emphasize that children should be considered for self-administration training and that the process does not have to be long or complicated.
Assuntos
Angioedemas Hereditários/complicações , Proteínas Inativadoras do Complemento 1/administração & dosagem , Adolescente , Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1 , Humanos , Masculino , Educação de Pacientes como Assunto , AutoadministraçãoRESUMO
NADPH oxidase plays a central role in mediating oxidative stress during heart, liver, and lung ischemia/reperfusion injury, but limited information is available about NADPH oxidase in renal ischemia/reperfusion injury. Our aim was to investigate the activation of NADPH oxidase in a swine model of renal ischemia/reperfusion damage. We induced renal ischemia/reperfusion in 10 pigs, treating 5 of them with human recombinant C1 inhibitor, and we collected kidney biopsies before ischemia and 15, 30, and 60 min after reperfusion. Ischemia/reperfusion induced a significant increase in NADPH oxidase 4 (NOX-4) expression at the tubular level, an upregulation of NOX-2 expression in infiltrating monocytes and myeloid dendritic cells, and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis along with a marked upregulation of NADPH-dependent superoxide generation. This burden of oxidative stress was associated with an increase in tubular and interstitial expression of the myofibroblast marker α-smooth muscle actin (α-SMA). Interestingly, NOX-4 and NOX-2 expression and the overall NADPH oxidase activity as well as α-SMA expression and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis were strongly reduced in C1-inhibitor-treated animals. In vitro, when we incubated tubular cells with the anaphylotoxin C3a, we observed an enhanced NADPH oxidase activity and α-SMA protein expression, which were both abolished by NOX-4 silencing. In conclusion, our findings suggest that NADPH oxidase is activated during ischemia/reperfusion in a complement-dependent manner and may play a potential role in the pathogenesis of progressive renal damage in this setting.
Assuntos
Proteínas do Sistema Complemento/metabolismo , Células Dendríticas/fisiologia , Túbulos Renais/irrigação sanguínea , NADPH Oxidases/metabolismo , Traumatismo por Reperfusão/enzimologia , Actinas/genética , Actinas/metabolismo , Animais , Células Cultivadas , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteína Inibidora do Complemento C1 , Complemento C3a/metabolismo , Desoxiadenosinas/biossíntese , Desoxiadenosinas/genética , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Modelos Animais , Estresse Oxidativo , RNA Interferente Pequeno/genética , Traumatismo por Reperfusão/imunologia , Sus scrofaRESUMO
BACKGROUND: Nanofiltered C1 inhibitor (human) is approved in the United States for routine prophylaxis of angioedema attacks in patients with hereditary angioedema, a rare disease caused by a deficiency of functional C1 inhibitor. OBJECTIVE: To assess the safety of escalating doses of nanofiltered C1 inhibitor (human) in patients who were not adequately controlled on the indicated dose (1000 U every 3 or 4 days). METHODS: Eligible patients had >1 attack/month over the 3 months before the trial. Doses were escalated to 1500 U every 3 or 4 days for 12 weeks, at which point, the patients were evaluated. If treatment was successful (≤1 attack/mo) or at the investigator's discretion, the patients entered a 3-month follow-up period. The patients with an average of >1 attack/month were eligible for further escalation to 2000 U and then 2500 U. RESULTS: Twenty patients started at 1500 U; 13 were escalated to 2000 U, and 12 were escalated to 2500 U. Eighteen patients reported adverse events. Two patients reported 4 serious adverse events (cerebral cystic hygroma, laryngeal angioedema attack, anemia, and bile duct stone) that were considered by investigators to be unrelated to treatment. Notably, there were no systemic thrombotic events or discontinuations due to adverse events. Fourteen patients were treated successfully (70%), continued to the follow-up period at the investigator's discretion, or experienced a reduction in attacks of >1.0/month. CONCLUSIONS: Dose escalation of nanofiltered C1 inhibitor (human) up to 2500 U was well tolerated and reduced attack frequency in the majority of patients.
Assuntos
Angioedemas Hereditários/prevenção & controle , Proteínas Inativadoras do Complemento 1/administração & dosagem , Complemento C1s/antagonistas & inibidores , Adolescente , Adulto , Idoso , Algoritmos , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/enzimologia , Angioedemas Hereditários/imunologia , Proteínas Inativadoras do Complemento 1/efeitos adversos , Proteína Inibidora do Complemento C1 , Complemento C1s/metabolismo , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. OBJECTIVE: To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. METHODS: Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. RESULTS: Median (95% confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P = .031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P = .003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P = .078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P = .005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. CONCLUSION: Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1/administração & dosagem , Inativadores do Complemento/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Adolescente , Adulto , Idoso , Angioedemas Hereditários/sangue , Angioedemas Hereditários/imunologia , Animais , Animais Geneticamente Modificados , Proteínas Inativadoras do Complemento 1/deficiência , Proteínas Inativadoras do Complemento 1/genética , Proteína Inibidora do Complemento C1 , Inativadores do Complemento/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Coelhos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Inquéritos e Questionários , Escala Visual Analógica , Adulto JovemRESUMO
Consensus meetings and the resulting recommendations shape treatment choices in rare diseases such as hereditary angioedema (HAE) because they combine the experience of prescribing physicians and the patients who are receiving therapy. Self-administration of HAE therapy was recognised as a potential treatment option in the first consensus publication in 2003. Recent studies have confirmed that self-administration of therapy resolves attacks quickly, safely and minimises burden of disease; however, the discovery of inconsistent treatment approaches is a concern and warrants investigation into the barriers that prevent adherence with current recommendations.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteínas Inativadoras do Complemento 1/administração & dosagem , Conferências de Consenso como Assunto , Guias como Assunto , Humanos , Cooperação do Paciente , Autoadministração/métodos , Autoadministração/normasRESUMO
At an international hereditary angioedema (HAE) expert meeting, results from a survey were used to guide discussion on how best to advise patients on self-administering intravenous C1 esterase inhibitor therapy. Treatment differences across Europe were highlighted, together with the practicalities of self-administration and useful resources for patients in the future. The international HAE experts noted an increase in the uptake of self-administration, with patients being trained by nursing staff. All patients who are willing and able to self-administer should be offered this treatment option and patients should be encouraged to treat attacks early. Several initiatives were suggested regarding support for patients who self-administer therapy, including a 24-hour helpline and home care agencies.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/enfermagem , Proteínas Inativadoras do Complemento 1/administração & dosagem , Europa (Continente) , Humanos , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/normas , Autoadministração/métodos , Autoadministração/enfermagem , Inquéritos e QuestionáriosRESUMO
AIMS: To characterize the pharmacokinetics (PK) of recombinant human C1 inhibitor (rhC1INH) in healthy volunteers and hereditary angioedema (HAE) patients. METHODS: Plasma levels of C1INH following 294 administrations of rhC1INH in 133 subjects were fitted using nonlinear mixed-effects modelling. The model was used to simulate maximal C1INH levels for the proposed dosing scheme. RESULTS: A one-compartment model with Michaelis-Menten elimination kinetics described the data. Baseline C1INH levels were 0.901 [95% confidence interval (CI): 0.839-0.968] and 0.176 U ml(-1) (95% CI: 0.154-0.200) in healthy volunteers and HAE patients, respectively. The volume of distribution of rhC1INH was 2.86 l (95% CI: 2.68-3.03). The maximal rate of elimination and the concentration corresponding to half this maximal rate were 1.63 U ml(-1) h(-1) (95% CI: 1.41-1.88) and 1.60 U ml(-1) (95% CI: 1.14-2.24), respectively, for healthy volunteers and symptomatic HAE patients. The maximal elimination rate was 36% lower in asymptomatic HAE patients. Peak C1INH levels did not change upon repeated administration of rhC1INH. Bodyweight was found to be an important predictor of the volume of distribution. Simulations of the proposed dosing scheme predicted peak C1INH concentrations above the lower level of the normal range (0.7 U ml(-1)) for at least 94% of all patients. CONCLUSIONS: The population PK model for C1INH supports a dosing scheme on a 50 U kg(-1) basis up to 84 kg, with a fixed dose of 4200 U above 84 kg. The PK of rhC1INH following repeat administration are consistent with the PK following the first administration.
Assuntos
Proteínas Inativadoras do Complemento 1/farmacocinética , Angioedema Hereditário Tipos I e II/sangue , Modelos Biológicos , Ensaios Clínicos como Assunto , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Inativadoras do Complemento 1/uso terapêutico , Proteína Inibidora do Complemento C1 , Simulação por Computador , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Humanos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêuticoRESUMO
Hereditary angio-oedema (HAE) is a rare genetic disease caused by deficiency of complement C1 inhibitor. It is characterised by recurrent episodes of subcutaneous or submucosal oedema typically involving the extremities, bowel, face or larynx. Within the latest years it has become evident that the active mediator of HAE attacks is an increased level of bradykinin and various new treatment modalities have been developed. The aim of this paper is to give an update from the Danish HAE Comprehensive Care Centre on current treatment possibilities and address some of the challenges when diagnosing HAE.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Antagonistas de Receptor B2 da Bradicinina , Proteínas Inativadoras do Complemento 1/uso terapêutico , Adulto , Angioedemas Hereditários/complicações , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/patologia , Bradicinina/administração & dosagem , Bradicinina/análogos & derivados , Bradicinina/uso terapêutico , Proteínas Inativadoras do Complemento 1/administração & dosagem , Proteínas Inativadoras do Complemento 1/genética , Proteínas Inativadoras do Complemento 1/metabolismo , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/uso terapêutico , Diagnóstico Diferencial , Eritema/patologia , Feminino , Humanos , Calicreínas/antagonistas & inibidores , Edema Laríngeo/etiologia , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Receptor B2 da Bradicinina/administração & dosagem , Receptor B2 da Bradicinina/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêuticoAssuntos
Angioedemas Hereditários/prevenção & controle , Proteínas Inativadoras do Complemento 1/administração & dosagem , Angioedemas Hereditários/sangue , Angioedemas Hereditários/complicações , Quimioprevenção , Humanos , Complicações Intraoperatórias/prevenção & controle , Procedimentos Cirúrgicos Bucais , Fatores de TempoRESUMO
OBJECTIVE: Nanofiltered C1-inhibitor (C1INH-nf) is approved for prophylactic treatment of hereditary angioedema. This study assessed the efficacy and safety of C1INH-nf as prophylactic therapy in a large cohort of patients with hereditary angioedema. METHODS: An open-label multicenter extension study was performed involving 146 subjects with hereditary angioedema who were treated with C1INH-nf for up to 2.6 years in centers throughout the United States. Subjects were to be treated with C1INH-nf 1000 units every 3 to 7 days. The primary efficacy variable was the number of attacks of angioedema experienced. RESULTS: Subjects experienced a 93.7% reduction in attacks while taking prophylactic C1INH-nf (0.19 attacks per month; interquartile range, 0.00-0.64) compared with the historical rate of attacks. Some 87.7% reported an attack frequency of 1 or less attack per month during prophylactic C1INH-nf and 34.9% had no attacks during the study. Some 7.5% of subjects experienced relatively frequent attacks despite twice-weekly C1INH-nf. Although twice-weekly dosing was highly effective in most subjects, once-weekly dosing provided adequate control in a subgroup of subjects. No clinical characteristics predicted the response to prophylactic C1INH-nf, including historical attack frequency. C1INH-nf was well tolerated. CONCLUSION: Prophylactic C1INH-nf is highly effective and safe, and provides durable prophylaxis in the majority of patients with hereditary angioedema. The recommended dose of C1INH-nf 1000 units twice weekly is supported by this open-label study. Individual patients may benefit from further dose adjustment on the basis of response to therapy and individual treatment goals.