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2.
J Allergy Clin Immunol Pract ; 7(6): 1793-1802.e2, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30772477

RESUMO

BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.

4.
J Manag Care Spec Pharm ; 25(2): 148-151, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30698094

RESUMO

DISCLOSURES: No funding supported the writing of this commentary. The author reports personal fees from BioCryst, CSL Behring, Shire, and Pharming and grants from Ionis. He is chair of the US HAEA Medical Advisory Board and scientific advisor for HAE International.


Assuntos
Angioedema Hereditário Tipos I e II/tratamento farmacológico , Modelos Econômicos , Análise Custo-Benefício , Angioedema Hereditário Tipos I e II/economia , Angioedema Hereditário Tipos I e II/fisiopatologia , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos
6.
JAMA ; 320(20): 2108-2121, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30480729

RESUMO

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P < .001); -1.44 (95% CI, -1.84 to -1.04; P < .001); and -1.71 (95% CI, -2.09 to -1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805.

7.
J Allergy Clin Immunol Pract ; 6(4): 1132-1141, 2018 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30033914

RESUMO

Angioedema is an acute swelling of the deeper layers of the skin or mucosa resulting from a transient increase in vascular permeability. Angioedema can occur in the absence or presence of hives, be hereditary or acquired, and be caused by various potential mediators, including histamine and bradykinin. Bradykinin-mediated angioedema can be difficult to diagnose but is responsible for a disproportionate percentage of the serious morbidity and mortality associated with angioedema. Our understanding of the basic biology of angioedema has dramatically expanded over recent years. The classification of angioedema has correspondently undergone major changes. Optimal management of patients with angioedema requires that an accurate diagnosis be established and that treatment be tailored to the patient's specific form of angioedema. In this article, we review the biology of bradykinin-mediated angioedema as well as the clinical approach to the evaluation of angioedema with a focus on bradykinin-mediated angioedema. Recognizing how the underlying pathophysiology and mechanisms of bradykinin dysregulation contribute to angioedema can help guide the clinical approach to the patient.

8.
Clin Exp Allergy ; 48(10): 1325-1332, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29998524

RESUMO

BACKGROUND: Long-term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma-derived C1-esterase inhibitor (C1-INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention. OBJECTIVE: To characterize the population pharmacokinetics of C1-INH (SC) (HAEGARDA® ; CSL Behring) in healthy volunteers and HAE patients, and assess the variability and influence of covariates on pharmacokinetics. METHODS: C1-INH functional activity data obtained after administration of various C1-INH (intravenous; IV) and C1-INH (SC) doses from 1 study in healthy volunteers (n = 16) and 2 studies in subjects with HAE (n = 108) were pooled to develop a population pharmacokinetic model (NONMEM v7.2). Pharmacokinetic parameters derived from steady-state simulations based on the final model were also evaluated. RESULTS: C1-INH functional activity following C1-INH (SC) administration was described by a linear one-compartment model with first-order absorption and elimination, with inter-individual variability in all parameters tested. The mean population bioavailability of C1-INH (SC), and pharmacokinetic parameters for clearance (CL), volume of distribution, and absorption rate were estimated to be ~43%, 1.03 mL/hour/kg, 0.05 L/kg and 0.0146 hour-1 , respectively. The effect of bodyweight on CL of C1-INH functional activity was included in the final model, estimated to be 0.74. Steady-state simulations of C1-INH functional activity vs time profiles in 1000 virtual HAE patients revealed higher minimum functional activity (Ctrough ) levels after twice-weekly dosing with 40 IU/kg (~40%) and 60 IU/kg (~48%) compared with 1000 IU IV (~30%). Based on the population pharmacokinetic model, the median time to peak concentration was ~59 hours and the median apparent plasma half-life was ~69 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Twice-weekly bodyweight-adjusted dosing of C1-INH (SC) exhibits linear pharmacokinetics and dose-dependent increases in Ctrough levels at each dosing interval. In this analysis, SC dosing led to maintenance of higher Ctrough levels than IV dosing.

9.
Clin Exp Allergy ; 48(11): 1429-1438, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29957871

RESUMO

BACKGROUND: The lack of specific biomarkers makes the diagnosis of hereditary angioedema (HAE) with normal levels of C1-inhibitor (C1INH) protein (HAE-nl-C1INH) and idiopathic non-histaminergic angioedema (INHA) difficult. Confirming or excluding these diagnoses is a significant challenge for clinicians evaluating patients with angioedema. OBJECTIVE: To develop a reliable biomarker that would aid the diagnosis of HAE-nl-C1INH and INHA. METHODS: A total of 154 consecutive patients referred for angioedema at a single centre were enrolled and evaluated. Subjects were clinically phenotyped based on clinical history and response to treatment by clinicians blinded to laboratory assay results. Plasma kallikrein activity was measured by the cleavage of the fluorometric substrate Z-Phe-Arg-AMC-HCL in plasma samples stimulated ex vivo with submaximal doses of dextran sulphate. RESULTS: Stimulated plasma kallikrein activity (mean relative fluorescence units/min ± SD) was significantly increased in both HAE-nl-C1INH (1804 ± 600) and INHA (1579 ± 371) subjects compared to non-swelling controls (171 ± 46) and histaminergic angioedema (133 ± 30) subjects. Using a threshold cut-off based on the normal controls, HAE-nl-C1INH and INHA subjects could be differentiated from histaminergic angioedema subjects with high sensitivity (negative predictive value 86%-89%) and specificity (positive predictive value 80%-100%). CONCLUSION AND CLINICAL RELEVANCE: The stimulated kallikrein activity assay allows differentiation of bradykinin- from histamine-mediated angioedema. The assay could feasibly be considered as a potential clinical tool for the diagnosis of bradykinin-mediated angioedema.

11.
Allergy Asthma Proc ; 39(3): 212-223, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29669666

RESUMO

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.

12.
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).

13.
J Allergy Clin Immunol ; 141(3): 884-885, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29410040
14.
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.

15.
Immunol Allergy Clin North Am ; 37(3): 527-539, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687107

RESUMO

Hereditary angioedema (HAE) is a rare autosomal dominant disease clinically characterized by recurrent, often unpredictable attacks of subcutaneous and mucosal swelling. Acute episodes are debilitating, painful, disfiguring, and potentially fatal. HAE type I and type II result from a deficiency in the plasma level of functional C1 inhibitor. HAE with normal levels of C1 inhibitor has been recognized. There is evidence that contact activation underlies the recurrent attacks of swelling. This article reviews laboratory parameters to detect contact system activation and implications for diagnosis of HAE and other forms of bradykinin-mediated angioedema.


Assuntos
Angioedema/diagnóstico , Angioedema/etiologia , Angioedema/metabolismo , Biomarcadores , Bradicinina/metabolismo , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Transdução de Sinais
16.
Ann Allergy Asthma Immunol ; 118(4): 456-460.e1, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28283277

RESUMO

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare, life-threatening disease that imposes a significant burden on affected patients. 17α-alkylated androgens (anabolic androgens) decrease attack frequency and severity but carry the risk of potentially serious dose-related adverse effects. Despite the emergence of targeted therapies for HAE, continued anabolic androgen use has been driven in part by their low cost. OBJECTIVE: To examine the hidden cost of anabolic androgen use related to the risk of developing non-HAE comorbidities. METHODS: Patients with HAE were identified in the Southern California Kaiser Permanente database using clinical and laboratory findings compatible with HAE. These patients were stratified into anabolic androgen exposed and nonexposed groups. Matched controls were selected from the Kaiser database who did not have HAE or anabolic androgen exposure. Using multivariate analysis, we determined the number of non-HAE comorbidities linked to anabolic androgen use. We next determined the association between dosing and increasing exposure to anabolic androgens and the likelihood of having various comorbidities. RESULTS: Patients with HAE exposed to anabolic androgens had a 28% increase (P = .04) in non-HAE comorbidities when compared with their matched (nonexposed) controls. With each gram per month increase in exposure, a 12% increase in non-HAE comorbidities is observed (P < .01). The most commonly occurring non-HAE comorbidities were psychiatric, muscle cramps, obesity, and hyperlipidemia. CONCLUSION: Our data suggest that long-term anabolic androgen use enhances the risk of developing comorbid health conditions, thus amplifying the cost of care. Our report provides additional support for the preferred use of newer, targeted therapies for the management of HAE.


Assuntos
Anabolizantes/uso terapêutico , Androgênios/uso terapêutico , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Adolescente , Adulto , Anabolizantes/administração & dosagem , Anabolizantes/efeitos adversos , Anabolizantes/economia , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Androgênios/economia , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Proteína Inibidora do Complemento C1/economia , Proteína Inibidora do Complemento C1/uso terapêutico , Custos de Medicamentos , Feminino , Angioedema Hereditário Tipos I e II/diagnóstico , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
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
18.
J Allergy Clin Immunol ; 140(1): 101-108.e3, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28279492

RESUMO

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD. OBJECTIVE: We sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD. METHODS: Blood and nasal scrapings were collected at baseline, during reactions, and after completion of ketorolac/aspirin challenge/desensitization in 12 patients with AERD. ILC2s and eosinophils were quantitated by means of flow cytometry. Urine was also collected, and quantification of PGD2 metabolite and leukotriene E4 levels was done by using ELISA. Baseline and nonsteroidal anti-inflammatory drug reaction clinical data were correlated with cell changes. RESULTS: ILC2 numbers significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in 2 patients without AERD. Furthermore, eosinophil numbers decreased in blood concurrently with significant increases in urinary PGD2 metabolite and leukotriene E4 levels. The magnitude of increases in nasal mucosal ILC2 numbers positively correlated with maximum symptom scores during challenges. Furthermore, blood ILC2 numbers during the reaction correlated with time for the reaction to resolve, possibly reflecting reaction severity. CONCLUSIONS: ILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.


Assuntos
Asma Induzida por Aspirina/imunologia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Linfócitos/imunologia , Mucosa Nasal/imunologia , Adulto , Idoso , Asma Induzida por Aspirina/sangue , Asma Induzida por Aspirina/urina , Contagem de Células , Dessensibilização Imunológica , Dinoprosta/urina , Feminino , Humanos , Cetorolaco/administração & dosagem , Leucotrieno E4/urina , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/citologia
19.
J Allergy Clin Immunol Pract ; 5(2): 442-447.e1, 2017 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27818136

RESUMO

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.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/uso terapêutico , Bradicinina/análogos & derivados , Serviços de Assistência Domiciliar , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioedemas Hereditários/epidemiologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Bradicinina/administração & dosagem , Bradicinina/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/administração & dosagem , Pessoal de Saúde , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Preferência do Paciente , Estudos Prospectivos , Autoadministração , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia , Escala Visual Analógica , Adulto Jovem
20.
J Allergy Clin Immunol Pract ; 5(1): 128-134.e4, 2017 Jan - Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27665386

RESUMO

BACKGROUND: Emergency department (ED) management of hereditary angioedema (HAE) has been hindered by misdiagnosis and limited treatment options. Food and Drug Administration approval of 4 on-demand HAE therapies starting in 2009 and the publication of ED guidelines for angioedema management in 2014 should facilitate improvement of HAE management in the ED. OBJECTIVE: The objective of this study was to identify patient-reported areas for improvement in ED management of HAE attacks. METHODS: Patients with self-reported HAE with C1 inhibitor deficiency who attended the 2015 HAE Association Patient Summit were asked to complete an anonymous 30-question survey. Questions addressed patient characteristics and HAE management in the ED. RESULTS: Patients indicated that understanding of HAE in the ED needed improvement (99%, 104 of 105 patients). Recognition of HAE as a diagnosis (48%, 50 of 105 patients), appreciation of HAE as a serious disease (45%, 47 of 105 patients), and medication management (59%, 62 of 105 patients) were identified as areas needing improvement. Among 39 patients who required ED care within the last year, 6 did not receive any HAE-targeted therapy, and treatment with corticosteroids (n = 3), epinephrine (n = 2), and antihistamines (n = 7) was reported. Among 68 patients whose treatment plan was to receive home on-demand therapy, 26 required ED care because of an inability to receive on-demand therapy at home as outlined in their treatment plan. Having a treatment plan was associated with a greater likelihood of receiving HAE therapy in the ED (99% vs 74%, P = .002). CONCLUSION: HAE management in the ED can be improved with a focus on recognition of HAE attacks and administration of effective HAE therapies.


Assuntos
Angioedemas Hereditários/diagnóstico por imagem , Angioedemas Hereditários/epidemiologia , Serviço Hospitalar de Emergência , Satisfação do Paciente , Melhoria de Qualidade , Adolescente , Angioedemas Hereditários/terapia , Criança , Pré-Escolar , Erros de Diagnóstico , Gerenciamento Clínico , Serviços Médicos de Emergência , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Inquéritos e Questionários , Estados Unidos , United States Food and Drug Administration
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