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2.
Orphanet J Rare Dis ; 13(1): 180, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30314518

RESUMO

BACKGROUND: Real-world data on usage and associated outcomes with hereditary angioedema (HAE)-specific medications introduced to the United States (US) market since 2009 are very limited. The purpose of this retrospective study was to evaluate real-world treatment patterns of HAE-specific medications in the US and to assess their impact on healthcare resource utilization (HCRU). This analysis used IMS PharMetrics PlusTM database records (2006-2014) of patients with HAE, ≥1 insurance claim for an HAE-specific medication, and continuous insurance enrollment for ≥3 months following the first HAE prescription claim. RESULTS: Of 631 total patients, 434 (68.8%) reported C1-INH(IV) use; 396 (62.8%) reported using ecallantide and/or icatibant. There were 306 episodes of prophylactic use of C1-INH(IV) (defined by continuous refills averaging ≥1500 IU/week for ≥13 weeks) in 155 patients; use of ≥1 on-demand rescue medication was implicated during 53% (163/306) of those episodes. Sixty-eight (20.2%) of 336 C1-INH(IV) users eligible for the HCRU analysis were hospitalized at least once, and 191 (56.8%) visited the emergency department (ED). Eighteen patients (5.4%) had a central venous access device (CVAD); of these, 5 (27.7%) required hospitalization and 14 (77.7%) had an ED visit. The adjusted relative risk of hospitalization and/or ED visits for patients with a CVAD was 2.6 (95% CI: 0.17, 39.23) compared to C1-INH(IV) users without a CVAD. CONCLUSIONS: Despite widespread availability of modern HAE medications in the US, we identified a subset of patients requiring long-term prophylaxis who continue to be burdened by frequent rescue medication usage and/or complications related to the use of CVADs for intravenous HAE medication.

3.
J Allergy Clin Immunol Pract ; 6(5): 1733-1741.e3, 2018 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29391286

RESUMO

BACKGROUND: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). OBJECTIVE: The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. METHODS: Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. CONCLUSIONS: In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on-demand treatment alone (placebo prophylaxis).

4.
CPT Pharmacometrics Syst Pharmacol ; 7(3): 158-165, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29316335

RESUMO

Subcutaneous C1-inhibitor (HAEGARDA, CSL Behring), is a US Food and Drug Administration (FDA)-approved, highly concentrated formulation of a plasma-derived C1-esterase inhibitor (C1-INH), which, in the phase III Clinical Studies for Optimal Management in Preventing Angioedema with Low-Volume Subcutaneous C1-inhibitor Replacement Therapy (COMPACT) trial, reduced the incidence of hereditary angioedema (HAE) attacks when given prophylactically. Data from the COMPACT trial were used to develop a repeated time-to-event model to characterize the timing and frequency of HAE attacks as a function of C1-INH activity, and then develop an exposure-response model to assess the relationship between C1-INH functional activity levels (C1-INH(f)) and the risk of an attack. The C1-INH(f) values of 33.1%, 40.3%, and 63.1% were predicted to correspond with 50%, 70%, and 90% reductions in the HAE attack risk, respectively, relative to no therapy. Based on trough C1-INH(f) values for the 40 IU/kg (40.2%) and 60 IU/kg (48.0%) C1-INH (SC) doses, the model predicted that 50% and 67% of the population, respectively, would see at least a 70% decrease in the risk of an attack.

5.
Ann Allergy Asthma Immunol ; 119(1): 59-64, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668241

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms. OBJECTIVE: To better understand patient experiences with using C1-INH(IV), including level of satisfaction and types and frequency of complications. METHODS: Fifty adult members (≥18 years of age) of the US HAE Association who had HAE type I or II completed a self-administered internet survey. Eligible participants were experiencing at least 1 HAE attack per month and must have been receiving treatment with C1-INH(IV) as prophylaxis or acute therapy. RESULTS: Almost all respondents (n = 47; 94%) were using C1-INH(IV) for HAE prophylaxis. Most patients reported administration of C1-INH(IV) through a peripheral vein (n = 34) and 19 were currently (n = 17) or previously (n = 2) using a central venous port. Most respondents (62%) who used a peripheral vein to administer treatment reported having difficulty finding a usable vein or getting the infusion to work properly at least some of the time. Issues accessing veins, exhausted veins, and frequency of attacks were the main reasons physicians recommended ports to respondents. Although ports allow easier administration of therapy, 47% of respondents with ports experienced problems such as occlusion, thrombosis, and infection. Respondents using C1-INH prophylaxis reported a mean of 2.3 attacks per month during the previous 6 months. CONCLUSION: The survey results identified clinical challenges with IV HAE medication use, including venous access issues and ongoing monthly attack occurrence despite prophylactic C1-INH(IV) administration.


Assuntos
Proteína Inibidora do Complemento C1/administração & dosagem , Angioedema Hereditário Tipos I e II/epidemiologia , Angioedema Hereditário Tipos I e II/terapia , Satisfação do Paciente , Administração Intravenosa , Adolescente , Adulto , Idoso , Proteína Inibidora do Complemento C1/efeitos adversos , Progressão da Doença , Feminino , Pesquisas sobre Serviços de Saúde , Angioedema Hereditário Tipos I e II/diagnóstico , Angioedema Hereditário Tipos I e II/prevenção & controle , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Fenótipo , Pré-Medicação , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
6.
Allergy Rhinol (Providence) ; 8(1): 13-19, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28381322

RESUMO

BACKGROUND: The plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) is approved in the United States as an intravenous (IV) on-demand treatment for hereditary angioedema (HAE) attacks, and, in Europe, as on demand and short-term prophylaxis. OBJECTIVE: This analysis evaluated Berinert Patient Registry data regarding IV pnfC1-INH used as long-term prophylaxis (LTP). METHODS: The international registry (2010-2014) collected prospective and retrospective usage, dosing, and safety data on individuals who used pnfC1-INH for any reason. RESULTS: The registry included data on 47 subjects (80.9% female subjects; mean age, 44.8 years), which reflected 4082 infusions categorized as LTP and a total of 430.2 months of LTP administration. The median absolute dose of pnfC1-INH given for LTP was 1000 IU (range, 500-3000 IU), with a median time interval between infusion and a subsequent pnfC1-INH-treated attack of 72.0 hours (range, 0.0-166.4 hours). Fifteen subjects (31.9%) had no pnfC1-INH-treated HAE attacks within 7 days after pnfC1-INH infusion for LTP; 32 subjects (68.1%) experienced 246 attacks, with rates of 0.06 attacks per infusion and 0.57 attacks per month. A total of 81 adverse events were reported in 16 subjects (34.0%) (0.02 events per infusion; 0.19 events per month); only 3 adverse events were considered related to pnfC1-INH (noncardiac chest pain, postinfusion headache, deep vein thrombosis in a subject with an IV port). CONCLUSION: In this international registry, IV pnf-C1-INH given as LTP for HAE was safe and efficacious, with a low rate of attacks that required pnfC1-INH treatment, particularly within the first several days after LTP administration.

7.
N Engl J Med ; 376(12): 1131-1140, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28328347

RESUMO

BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).


Assuntos
Proteína Inibidora do Complemento C1/administração & dosagem , Angioedema Hereditário Tipos I e II/prevenção & controle , Adulto , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Angioedema Hereditário Tipos I e II/classificação , Humanos , Injeções Subcutâneas , Masculino , Risco , Autoadministração , Índice de Gravidade de Doença
9.
Ann Allergy Asthma Immunol ; 117(5): 508-513, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27788880

RESUMO

BACKGROUND: Limited data are available regarding C1 inhibitor (C1-INH) administration and anti-C1-INH antibodies. OBJECTIVE: To assess the incidence of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH) in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) and the comparative efficacy of pnfC1-INH in patients with and without antibodies. METHODS: In this multicenter, open-label study, patients with C1-INH-HAE (≥12 years of age) were given 20 IU/kg of pnfC1-INH per HAE attack that required treatment and followed up for 9 months. Blood samples were taken at baseline (day of first attack) and months 3, 6, and 9 and analyzed for inhibitory anti-C1-INH antibody (iC1-INH-Ab) and noninhibitory anti-C1-INH antibodies (niC1-INH-Abs). RESULTS: The study included 46 patients (69.6% female; mean age, 38.9 years; all white) who received 221 on-site pnfC1-INH infusions; most patients received 6 or fewer infusions. No patient tested positive (titer ≥1:50) for iC1-INH-Ab at any time during the study. Thirteen patients (28.2%) had detectable niC1-INH-Abs in 1 or more samples. Nine patients (19.6%) had detectable niC1-INH-Abs at baseline; 3 of these had no detectable antibodies after baseline. Of 10 patients (21.7%) with 1 or more detectable result for niC1-INH-Abs after baseline, 6 had detectable niC1-INH-Abs at baseline. Mean times to symptom relief onset and complete symptom resolution per patient were similar for those with or without anti-niC1-INH-Abs. CONCLUSION: Administration of pnfC1-INH was not associated with iC1-INH-Ab formation in this population. Noninhibitory antibodies were detected in some patients but fluctuated during the study independently of pnfC1-INH administration and appeared to have no effect on pnfC1-INH efficacy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01467947.


Assuntos
Angioedemas Hereditários/sangue , Angioedemas Hereditários/tratamento farmacológico , Anticorpos/sangue , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Adolescente , Adulto , Idoso , Angioedemas Hereditários/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
10.
J Emerg Med ; 50(4): 567-80.e1, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26826769

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by C1-esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema, which can be life-threatening if they occur in the upper airway. No head-to-head comparisons of different treatment options for acute HAE attacks are available. Because immediate symptom relief is critical for potentially life-threatening laryngeal attacks, it is important to determine the treatment option that provides optimal treatment response. OBJECTIVE: Review and compare data from clinical studies that evaluated the efficacy and safety of treatments for laryngeal HAE attacks. METHODS: We conducted an indirect comparison of clinical outcomes from prospective studies for treatment of 881 acute laryngeal attacks with plasma-derived C1-INH concentrate (pdC1-INH) at fixed doses (500 or 1000 U) or a body weight-adjusted dose (20 U/kg), recombinant C1-INH concentrate at a fixed dose (2100 U), or a body weight-adjusted dose (50 U/kg), icatibant (30 mg), or ecallantide (30 mg). Comparisons included time to onset of symptom relief and need for re-dosing or emergency procedures. RESULTS: The median time to onset of symptom relief ranged between 15 min and approximately 2 h, and was shortest with body weight-adjusted doses of pdC1-INH. The proportion of laryngeal attacks with re-dosing ranged between 0% and 72%. No re-dosing was needed after treatment with a single body weight-adjusted dose of pdC1-INH (48 attacks). CONCLUSIONS: Available data suggest that among different HAE treatments, body weight-adjusted pdC1-INH (20 U/kg) provides the most reliable treatment response for treatment of laryngeal HAE attacks.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/enzimologia , Proteína Inibidora do Complemento C1/uso terapêutico , Doenças da Laringe/tratamento farmacológico , Doenças da Laringe/enzimologia , Humanos , Resultado do Tratamento
11.
Allergy Asthma Proc ; 36(3): 218-24, 2015 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25803207

RESUMO

BACKGROUND: Although treatment with C1 esterase inhibitor (C1-INH) concentrate is well established for hereditary angioedema (HAE) attacks in general, data that assess its efficacy for cutaneous attack treatment are sparse. OBJECTIVE: To assess efficacy of plasma-derived, nanofiltered C1-INH concentrate for cutaneous attack treatment by comparing treated attacks from the uncontrolled I.M.P.A.C.T.2 study with historical data for untreated attacks. METHODS: Cutaneous attack data from patients with HAE who were treated for cutaneous edema with 20 IU/kg body weight C1-INH concentrate in the uncontrolled I.M.P.A.C.T.2 study (38 patients) were compared with data from untreated patients from an historical data base (46 patients) and included subset analyses for facial edema (treated group, 21 patients; untreated group, 33 patients) and peripheral edema (30 patients in each group). Average attack duration (AAD) per patient was the efficacy end point used to compare treated and untreated patients. Differences were assessed with a Wilcoxon test (primary analysis) and a log-rank test; AAD per patient was analyzed descriptively and graphically with Kaplan-Meier curves. RESULTS: The AAD per patient of all cutaneous attacks or facial and peripheral cutaneous attack subsets was significantly faster with C1-INH treatment than without treatment (Wilcoxon and log-rank tests, both p < 0.0001 for all comparisons). Mean AADs per patient for all, facial, and peripheral attacks were 2.04, 1.45, and 2.16 days, respectively, in the C1-INH-treated group, and were 3.74, 4.45, and 2.98 days, respectively, in the untreated group. Kaplan-Meier curves corroborated the observed group differences. CONCLUSION: Treatment of cutaneous HAE attacks (all attacks or facial and peripheral attack subsets) with 20 IU/kg C1-INH concentrate provided faster attack resolution compared with no treatment.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Adolescente , Adulto , Idoso , Angioedemas Hereditários/diagnóstico , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
12.
J Allergy Clin Immunol Pract ; 3(2): 213-9, 2015 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25609333

RESUMO

BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typically with off-label use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events. METHODS: A registry was initiated in April 2010 at 27 US and 4 EU sites to obtain both prospective and retrospective safety and usage data on subjects who were administered C1-INH (Berinert). RESULTS: As of May 10, 2013, data were available for 135 subjects and 3196 infusions. By subject, 67.4% were using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and prophylactic administration. Approximately half of the infusions (49.5%) were administered for prophylaxis and >90% were given by the patient or a caregiver in the home setting. A total of 299 adverse events were reported, for an overall rate of 0.09 events per infusion with only 6 considered related to C1-INH. Two thromboembolic events were reported, both in patients with prothrombotic risk factors. CONCLUSION: This large pool of real-world clinical usage data in HAE further supports the extensive safety profile of 2 Berinert formulations when used on demand and/or for prophylaxis in both home and health care settings. No evidence was found to suggest that Berinert is an independent, causative risk factor for thromboembolic events.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/prevenção & controle , Proteína Inibidora do Complemento C1/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Proteína Inibidora do Complemento C1/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Tromboembolia/induzido quimicamente , Adulto Jovem
13.
Transfusion ; 54(10): 2566-73, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24805006

RESUMO

BACKGROUND: For safe and efficacious treatment of hereditary angioedema, C1 esterase inhibitor (C1-INH) concentrates should have high purity and high amounts of functional protein. As no pharmacopoeia requirements exist for C1-INH concentrate lot release, biochemical characteristics as declared by the manufacturers may not be compared directly. This study compared the characteristics and purity profiles of four commercially available C1-INH concentrates. STUDY DESIGN AND METHODS: The analysis included one transgenic (Ruconest) and three plasma-derived (Berinert, Cetor, Cinryze) C1-INH concentrates. C1-INH antigen concentration was determined by nephelometry, total protein (specific activity) with a Bradford assay, purity by size-exclusion chromatography and gel electrophoresis, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was performed. RESULTS: Functionality (inversely proportional to antigen-to-activity ratio) was lowest for Ruconest (1.67), followed by Cetor (1.42), Berinert (1.24), and Cinryze (1.22). Specific activity (U/mg) and purity (%) were highest in Ruconest (12.13; 98.6) and Berinert (11.57; 97.0), followed by Cinryze (10.41; 89.5) and Cetor (9.01; 88.6). Main protein bands were found for all plasma-derived products at approximately 105 kDa, and for Ruconest, at approximately 98 kDa. Additional bands in the plasma-derived products were α1-antichymotrypsin, ceruloplasmin, Factor C3 (Cinryze/Cetor), and immunoglobulin heavy constant mu (Berinert). CONCLUSION: Ruconest has a very high purity profile but is not identical to the human C1-INH protein. Of the plasma-derived products, Berinert has the highest purity profile. The impact of the nontherapeutic proteins identified has not yet been evaluated. For harmonization of the analysis for drug release, we recommend the establishment of regulatory requirements for purity determination and the implementation of threshold levels in C1-INH concentrates.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/química , Proteína Inibidora do Complemento C1/uso terapêutico , Proteínas Sanguíneas/química , Comércio , Proteínas Inativadoras do Complemento 1/química , Proteínas Inativadoras do Complemento 1/uso terapêutico , Proteína Inibidora do Complemento C1/normas , Contaminação de Medicamentos , Humanos , Concentração Osmolar , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
14.
Clin Ther ; 36(4): 518-25, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24661784

RESUMO

BACKGROUND: Despite the worldwide obesity epidemic, there have been very few studies investigating the influence of body weight on treatment dosing and outcomes in patients with hereditary angioedema (HAE). OBJECTIVE: The purpose of this analysis was to determine whether the standard weight-based dosing recommendation of C1 esterase inhibitor (C1-INH) concentrate (20 IU/kg) is adequate in HAE patients with a high body mass index (BMI). METHODS: Data from patients treated for HAE attacks with 20 IU/kg of C1-INH concentrate were retrospectively analyzed from the open-label IMPACT2 study (International Multicenter Prospective Angioedema C1-INH Trial). Patients were categorized according to BMI as being normal body weight, overweight, or obese. Efficacy end points were time to onset of symptom relief and time to complete resolution of symptoms. The safety profile was evaluated according to adverse events occurring within 7 to 9 days of treatment. RESULTS: Of 57 patients, 24 (42%) were of normal body weight, 20 (35%) were overweight, and 13 (23%) were obese. Median (95% CI) time to onset of symptom relief was 0.37 hour (0.29-0.57) in normal-weight patients, 0.48 hour (0.39-0.53) in overweight patients, and 0.58 hour (0.41-0.94) in obese patients. Median time (95% CI) to complete resolution of symptoms was 15.2 hours (9.3-23.2) in normal-weight patients, 22.6 hours (11.3-44.6) in overweight patients, and 11.0 hours (5.6-23.6) in obese patients (differences not significant). There were no relevant differences in the incidence of adverse events in normal-weight patients (54%), overweight patients (30%), and obese patients (54%). CONCLUSIONS: Treatment of HAE attacks with weight-based doses of C1-INH concentrate provided reliable treatment response, regardless of body weight, in these patients with HAE.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Peso Corporal , Proteína Inibidora do Complemento C1/administração & dosagem , Doença Aguda , Adolescente , Adulto , Índice de Massa Corporal , Criança , Proteína Inibidora do Complemento C1/efeitos adversos , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Sobrepeso , Projetos de Pesquisa , Estudos Retrospectivos , Resultado do Tratamento
15.
Ann Allergy Asthma Immunol ; 111(3): 211-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23987198

RESUMO

BACKGROUND: C1 esterase inhibitor (C1-INH) concentrate is well established as effective therapy for hereditary angioedema (HAE). It is thought that treatment of an acute HAE attack with C1-INH as early as possible improves efficacy, but there are limited data from prospective studies supporting this recommendation. OBJECTIVE: To assess the effect of time to treatment (<6 vs ≥6 hours after start of an attack) with 20 U/kg of C1-INH concentrate on efficacy. METHODS: A post hoc analysis of time to treatment after start of an attack was performed for 2 studies with C1-INH concentrate: International Multicenter Prospective Angioedema C1-INH Trial (IMPACT) 1 (randomized, placebo-controlled) and IMPACT 2 (open-label, uncontrolled extension). Because of differences in study design, the data sets were analyzed separately. IMPACT 1 data were analyzed using Cox regression with hazard ratios (HRs). For IMPACT 2 data, linear regression was applied to evaluate whether earlier treatment leads to faster recovery. Descriptive statistics for treatment response were calculated for both studies. RESULTS: In IMPACT 1, treatment with C1-INH within less than 6 hours after start of an attack resulted in considerably shorter times to onset of symptom relief (HR, 3.36) and complete resolution (HR, 4.30) vs placebo. The benefit of C1-INH compared with placebo was reduced when administered after 6 or more hours (HRs, 1.18 for times to onset of symptom relief and 1.61 for complete resolution). Analysis of IMPACT 2 data indicated slower complete resolution of symptoms with later start of treatment. CONCLUSION: Early treatment with C1-INH (<6 hours) provides a better treatment response than late treatment (≥6 hours), supporting the international recommendation to treat HAE attacks as early as possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00168103 and NCT00292981.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/administração & dosagem , Inativadores do Complemento/administração & dosagem , Adolescente , Adulto , Idoso , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem
16.
Allergy Asthma Proc ; 34(4): 312-27, 2013 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23710659

RESUMO

Hereditary angioedema (HAE) due to C1 esterase inhibitor (HAE-C1-INH) deficiency is a rare genetic disorder presenting with recurrent episodes of skin swellings, abdominal pain attacks, and potentially fatal laryngeal edema. This study was designed to review the efficacy and safety of pasteurized, human, plasma-derived C1-INH concentrate for the treatment of patients with HAE-C1-INH. A systematic search of electronic databases up to December 2011 was performed without language or date restrictions. Two reviewers completed the study selection using predefined inclusion criteria, tabulated, and analyzed the data. The data were inappropriate for meta-analysis; thus, a qualitative synthesis was performed. We identified 89 studies (≍2000 patients) that investigated C1-INH. Replacement therapy with C1-INH significantly shortened time to onset of symptom relief in HAE attacks compared with placebo in a randomized controlled trial, and similar improvements were consistently reported in observational and descriptive studies, accompanied by improvements in patients' quality of life. C1-INH has been shown to be effective for patients receiving home therapy and short- and long-term prophylaxis. Treatment with C1-INH was generally well tolerated. Administration of C1-INH was not associated with transmission of viruses or development of autoantibodies irrespective of treatment duration. This research provides additional confirmation of the efficacy of C1-INH in the treatment and prevention of HAE attacks. C1-INH is generally safe and well tolerated and has an excellent safety record for over 25 years of clinical use.


Assuntos
Proteína Inibidora do Complemento C1/uso terapêutico , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Angioedema Hereditário Tipos I e II/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Proteína Inibidora do Complemento C1/efeitos adversos , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
17.
Pediatr Allergy Immunol ; 24(1): 54-60, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23173714

RESUMO

BACKGROUND: We analyzed the clinical response of pediatric and adolescent hereditary angioedema (HAE) patients to pdC1-INH in the International Multicenter Prospective Angioedema C1-INH Trials (I.M.P.A.C.T.) 1 and 2. METHODS: Patients included in this post hoc analysis of prospectively collected data were between 10 and 18 yr old with type I or II HAE and a documented history of abdominal or facial attacks. Patients received a single injection of pdC1-INH concentrate (Berinert(®) , CSL Behring, Marburg, Germany) 20 U/kg. Efficacy end-points were time from the administration of study drug to onset of symptom relief and time to complete relief of all symptoms. RESULTS: Seven pediatric patients were included in I.M.P.A.C.T.1 with only 1 attack analyzed per patient. Median time to onset of relief was 0.42 h and to complete resolution was 8.08 h. No patient experienced a worsening of symptoms during the 0-4-h assessment period. Nine patients who experienced a total of 115 attacks were included in the analysis of I.M.P.A.C.T.2. Abdominal attacks were rated as 'severe' more frequently than were other types of attacks. The number of attacks per patient ranged from 2 to 42, and study participation ranged from 1 to 38 months. Median times to onset of symptom relief and to complete symptom resolution were 0.49 h and 14.1 h, respectively. Of 4 treatment-emergent adverse events in both studies, only 2 were considered related to treatment. CONCLUSIONS: Study results showed that outcomes with pdC1-INH treatment of HAE in pediatric patients are comparable with outcomes in adults.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Adolescente , Idoso , Angioedemas Hereditários/fisiopatologia , Criança , Estudos de Coortes , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/efeitos adversos , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
18.
Adv Ther ; 29(10): 913-22, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23054691

RESUMO

INTRODUCTION: Prodromal symptoms commonly precede hereditary angioedema (HAE) attacks. There is continuing interest in evaluating prodromes as treatment indicators, but a paucity of relevant data. This study was designed to prospectively identify prodomal characteristics in patients voluntarily reporting such information around the time of seeking treatment for an acute HAE attack. METHODS: Twenty-eight patients with HAE were enrolled in this survey, which was conducted in the context of an open-label study of treatment of HAE attacks with plasma-derived C1-inhibitor concentrate. At the time of treatment, patients were encouraged to answer survey questions about prodromal symptoms preceding that particular HAE attack. RESULTS: Twenty-one patients provided prodromal information for 253 treated HAE attacks. Seventy-one percent of patients (15/21) reported prodromes. Three patients accounted for approximately 80% of the attacks and 89% of the reported prodromal symptoms. Prodromes were experienced before 67.6% (171/253) of attacks, with a mean of 1.4 prodromes per attack. Fatigue was the most frequent prodrome (42% of attacks), followed by nausea (26%), and flu-like symptoms (22%). The median duration of a prodrome before an attack was 12 h (range, 0.33-24 h). CONCLUSIONS: Despite many limitations in the study design, these findings confirm that prodromes are frequently associated with HAE attacks in many patients and occur sufficiently early to allow time for treatment initiation. The frequency of "false positive" prodromal symptoms remains undetermined, and the authors captured data only on attacks severe enough to warrant treatment. Additional well-designed prospective studies are clearly needed to continue investigating the potential clinical relevance of prodromes.


Assuntos
Angioedema Hereditário Tipos I e II/fisiopatologia , Sintomas Prodrômicos , Adolescente , Adulto , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Progressão da Doença , Fadiga/etiologia , Angioedema Hereditário Tipos I e II/complicações , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Náusea/etiologia , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
19.
Allergy Asthma Proc ; 33(5): 427-31, 2012 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23026185

RESUMO

C1-inhibitor (INH) concentrate, which is recommended as first-line treatment for acute hereditary angioedema (HAE) attacks in many countries, was recently approved in the United States. We sought to solicit patients' feedback about their health-related quality of life (HRQoL) while being treated with C1-INH concentrate for acute HAE attacks under real-world conditions, as well as the personal impact of the availability of C1-INH on lifestyle and mental health domains. Subjects enrolled in an open-label study of C1-INH at 20 U/kg for acute HAE attacks were invited to participate in a prospectively designed survey to solicit "real-time" patient responses that were collected via an interactive voice response service or online with a personal computer. Eighteen subjects submitted 60 quarterly HRQoL and treatment impact survey responses over 29 months. Seventeen of 18 patients responding reported mean short form 12 HRQoL scores that were within a normal range. More than one-half indicated that C1-INH availability made them feel somewhat or much better, and >80% reported having a better outlook on the future and feeling more secure about the danger of life-threatening attacks. These data confirm a high level of HRQoL and a positive impact in lifestyle and emotional domains among patients who were treated for acute attacks of HAE with C1-INH concentrate.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/administração & dosagem , Qualidade de Vida , Doença Aguda , Adolescente , Adulto , Criança , Proteína Inibidora do Complemento C1/uso terapêutico , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
20.
Allergy Asthma Proc ; 33(4): 354-61, 2012 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22856636

RESUMO

Placebo-controlled studies established the efficacy of replacement therapy with C1 esterase inhibitor (C1-INH) concentrate for treating single acute hereditary angioedema (HAE) attacks, but only limited data from prospective studies are available on repeated treatment of successive HAE attacks. This study evaluates the association between repeated treatments with 20 U/kg of C1-INH concentrate (Berinert; CSL Behring, Marburg, Germany) for HAE attacks at any body location and treatment response. In a post hoc analysis of an open-label extension study (International Multicenter Prospective Angioedema C1-INH Trial [I.M.P.A.C.T.2]), the association between repeated treatment with C1-INH and times to onset of symptom relief and complete resolution of HAE symptoms was assessed in patients who were treated for at least 15 attacks by linear regression on the ordinal attack number. Eighteen patients received C1-INH concentrate for at least 15 HAE attacks over a mean duration of 34 months. Demographic and baseline characteristics of these patients were similar to those of all patients in the study. The distribution of body locations and the intensity of HAE attacks were similar for each of the first 15 attacks and subsequent attacks. The extent of previous use of C1-INH concentrate had no effect on the time to onset of symptom relief, the time to complete resolution of HAE symptoms, or the time between attacks treated with C1-INH concentrate; the median of individual linear regression coefficients was not statistically significantly different from 0. Treatment with 20 U/kg of C1-INH concentrate provided consistent treatment response in patients treated for multiple successive HAE attacks at any body location. (Clinicaltrials.gov identifier: NCT00292981).


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/epidemiologia , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/efeitos adversos , Doença Aguda , Adolescente , Adulto , Criança , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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