RESUMO
PURPOSE: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV). METHODS: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD. RESULTS: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year. CONCLUSIONS: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.
Assuntos
Imunoglobulinas Intravenosas/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/etiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/imunologia , Resultado do Tratamento , 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
BACKGROUND: Hereditary angioedema is a rare genetic disorder characterized by acute, intermittent, and potentially life-threatening attacks of edema of the skin and mucosa. We evaluated ecallantide, a newly developed recombinant plasma kallikrein inhibitor, for the treatment of acute attacks of angioedema. METHODS: In this double-blind, placebo-controlled trial, patients with hereditary angioedema presenting with an acute attack were randomly assigned, in a 1:1 ratio, to receive subcutaneous ecallantide, at a dose of 30 mg, or placebo. Two measures of patient-reported outcomes were used to assess the response: treatment outcome scores, which range from +100 (designated in the protocol as significant improvement in symptoms) to -100 (significant worsening of symptoms), and the change from baseline in the mean symptom complex severity score, which range from +2 (representing a change from mild symptoms at baseline to severe symptoms after) to -3 (representing a change from severe symptoms at baseline to no symptoms after). The primary end point was the treatment outcome score 4 hours after study-drug administration. Secondary end points included the change from baseline in the mean symptom complex severity score at 4 hours and the time to significant improvement. RESULTS: A total of 71 of the 72 patients completed the trial. The median treatment outcome score at 4 hours was 50.0 in the ecallantide group and 0.0 in the placebo group (interquartile range [IQR], 0.0 to 100.0 in both groups; P=0.004). The median change in the mean symptom complex severity score at 4 hours was -1.00 (IQR, -1.50 to 0.00) with ecallantide, versus -0.50 (IQR, -1.00 to 0.00) with placebo (P=0.01). The estimated time to significant improvement was 165 minutes with ecallantide versus more than 240 minutes with placebo (P=0.14). There were no deaths, treatment-related serious adverse events, or withdrawals owing to adverse events. CONCLUSIONS: Four hours after administration of ecallantide or placebo for acute attacks of angioedema in patients with hereditary angioedema, patient-reported treatment outcome scores and mean symptom complex severity scores were significantly better with ecallantide than with placebo. (Funded by Dyax; ClinicalTrials.gov number, NCT00262080.)
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Calicreínas/antagonistas & inibidores , Peptídeos/uso terapêutico , Doença Aguda , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Peptídeos/efeitos adversos , Estatísticas não Paramétricas , Adulto JovemRESUMO
BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening. METHODS: We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor group and 33 in the placebo group) were given one or two intravenous injections of the study drug (1000 units each). The primary end point was the time to the onset of unequivocal relief. The second study was a crossover trial involving 22 subjects with hereditary angioedema that compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo during two 12-week periods. The primary end point was the number of attacks of angioedema per period, with each subject acting as his or her own control. RESULTS: In the first study, the median time to the onset of unequivocal relief from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate but longer than 4 hours in those given placebo (P=0.02). In the second study, the number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who received the C1 inhibitor concentrate also had significant reductions in both the severity and the duration of attacks, in the need for open-label rescue therapy, and in the total number of days with swelling. CONCLUSIONS: In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/prevenção & controle , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Doença Aguda , Adulto , Análise de Variância , Criança , Proteína Inibidora do Complemento C1/efeitos adversos , Inativadores do Complemento/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Nanotecnologia , Modelos de Riscos Proporcionais , UltrafiltraçãoRESUMO
BACKGROUND: Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS: In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS: A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS: In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Antagonistas de Receptor B2 da Bradicinina , Bradicinina/análogos & derivados , Doença Aguda , Adulto , Bradicinina/administração & dosagem , Bradicinina/efeitos adversos , Bradicinina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Análise de Intenção de Tratamento , Masculino , Estatísticas não Paramétricas , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND: The efficacy of recombinant human C1 inhibitor (rhC1INH) for the treatment of patients with acute hereditary angioedema (HAE) attacks has been demonstrated in 2 randomized, double-blind, placebo-controlled studies. OBJECTIVE: To assess the safety and efficacy of rhC1INH for repeated treatment of acute attacks of HAE. METHODS: In this open-label extension study, patients with eligible HAE attacks were treated with an intravenous 50-U/kg dose of rhC1INH with an option for an additional dose of 50 U/kg based on clinical response. Time to beginning of relief was assessed by patients using a 100-mm visual analogue scale (VAS). Safety evaluation was based on the clinical laboratory results and adverse events. RESULTS: Sixty-two patients were treated for 168 attacks (range, 1-8 attacks per patient). A total of 90% of the attacks were treated with a single 50-U/kg dose of rhC1INH. Median times to beginning of symptom relief for the first 5 attacks were 37 to 67 minutes. More than 90% of attacks responded within 4 hours after treatment with rhC1INH. There was no requirement for increased dosing with successive treatments. Thirty-nine patients (63%) reported at least 1 treatment-emergent adverse event, with most events rated mild to moderate. Seven severe treatment-emergent adverse events were reported, and all were considered to be unrelated to treatment with rhC1INH. CONCLUSION: The results of this open-label extension support continued efficacy of rhC1INH after repeated treatments for subsequent HAE attacks. There was no increase in adverse event reporting after repeated exposure to rhC1INH.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Adolescente , Adulto , Angioedemas Hereditários/imunologia , Proteína Inibidora do Complemento C1/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Hereditary angioedema (HAE) is a rare disease caused by C1INH gene mutations, which leads to a deficiency or dysfunction of C1 inhibitor (C1 INH), resulting in recurrent episodes of severe and potentially life-threatening edema. OBJECTIVE: To evaluate the efficacy and safety of repeat use of nanofiltered C1 esterase inhibitor (human) (C1 INH-nf) for the short-term treatment of HAE attacks. METHODS: In this open-label study, patients received C1 INH-nf, 1,000 U intravenously, for the treatment of HAE attacks. Efficacy end points included the proportion of attacks with unequivocal relief of the defining symptom within 1 and 4 hours after receiving study drug and time to beginning of relief of the defining symptom. Safety was monitored through adverse event reporting, vital signs measurements, and laboratory testing. RESULTS: A total of 113 patients were enrolled in the study from September 21, 2006, through March 31, 2009, and received 885 doses of C1 INH-nf. A total of 609 HAE attacks were treated with C1 INH-nf, and the numbers of attacks achieving unequivocal relief of the defining symptom within 1 and 4 hours after the start of the first dose were 412 (68%) and 529 (87%), respectively. Of 101 patients treated for an attack during the study period, 80 achieved unequivocal relief of their first attack within 4 hours after study medication (response rate, 79%); median time to the beginning of unequivocal relief was 0.75 hour. C1 INH-nf was safe and well tolerated. CONCLUSIONS: This open-label study demonstrates the efficacy and safety of C1 INH-nf for short-term treatment of HAE attacks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438815.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/uso terapêutico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Proteína Inibidora do Complemento C1/administração & dosagem , Inativadores do Complemento/administração & dosagem , Feminino , Filtração/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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 JovemRESUMO
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 JovemRESUMO
BACKGROUND: Hereditary angioedema (HAE) is a rare disorder characterized by recurrent angioedema attacks. Ecallantide, a novel plasma kallikrein inhibitor, inhibits production of bradykinin, the key mediator of these angioedema attacks. OBJECTIVE: We sought to further characterize the safety and efficacy of ecallantide for HAE attacks by performing an integrated analysis of pooled data from 2 phase 3 studies. METHODS: An integrated analysis was conducted with data from 2 randomized, double-blind, placebo-controlled studies in which patients with HAE (age ≥10 years) received 30 mg of subcutaneous ecallantide or placebo within 8 hours of onset of a moderate-to-severe attack at any anatomic site. Efficacy was evaluated by using validated patient-reported outcome measures: the Mean Symptom Complex Severity (MSCS) score and the Treatment Outcome Score (TOS). RESULTS: Compared with placebo, ecallantide resulted in significantly greater reduction in MSCS scores from baseline to 4 hours after dosing (ecallantide [mean ± SD], -0.97 ± 0.78; placebo, -0.47 ± 0.71; P < .001) and a significantly greater increase in TOSs at 4 hours (ecallantide, 55.5 ± 46.5; placebo, 20.0 ± 58.9; P < .001). Significantly greater symptomatic improvement over placebo occurred through 24 hours after dosing (MSCS score, P = .028; TOS, P = .039). Ecallantide demonstrated efficacy at all attack sites. The incidence of treatment-emergent adverse events was similar between groups. CONCLUSIONS: This integrated analysis supports and expands on the results of the phase 3 studies. Ecallantide appears to be effective and well tolerated for the treatment of HAE attacks.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Peptídeos/uso terapêutico , Doença Aguda , Adulto , Idoso , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The For Angioedema Subcutaneous Treatment (FAST)-3 study was a phase III, randomized, double-blind, placebo-controlled study of icatibant (bradykinin B(2) receptor antagonist) in subjects with hereditary angioedema (HAE) resulting from C1-INH deficiency or dysfunction (type I/II). OBJECTIVE: To investigate icatibant efficacy and safety in subjects with acute HAE attacks. METHODS: Subjects with moderate to very severe cutaneous or abdominal symptoms received icatibant (n = 43) or placebo (n = 45). Five subjects with laryngeal (mild-to-moderate) first attacks received icatibant (n = 3) or placebo (n = 2), and 5 subjects with severe laryngeal first attacks received open-label icatibant. RESULTS: Cutaneous or abdominal attacks: icatibant significantly reduced median times (vs placebo) to 50% or more reduction in symptom severity (2.0 vs 19.8 hours; P < .001, primary endpoint), onset of primary symptom relief (1.5 vs 18.5 hours; P < .001, key secondary endpoint), or almost complete symptom relief (8.0 vs 36.0 hours; P = .012) and provided a shorter time to initial symptom relief (0.8 vs 3.5 hours; P < .001). For laryngeal attacks, median time to 50% or more reduction in symptom severity was 2.5 hours (icatibant) and 3.2 hours (placebo). No icatibant-treated subject required rescue medication before symptom relief occurred. The incidence of adverse events (AEs) was similar in icatibant- and placebo-treated subjects (41% and 52%, respectively). All icatibant-treated subjects experienced injection site reactions, but none reported clinically relevant changes in safety parameters or serious AEs. CONCLUSIONS: FAST-3 demonstrated that icatibant was effective and generally well tolerated in subjects with acute HAE attacks. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00912093.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Antagonistas de Receptor B2 da Bradicinina , Bradicinina/análogos & derivados , Adulto , Bradicinina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Estimativa de Kaplan-Meier , MasculinoRESUMO
BACKGROUND: hereditary angioedema (HAE) is a rare disorder characterized by a quantitative or functional deficiency of C1 esterase inhibitor (C1-INH), resulting in periodic attacks of acute edema at various body locations. The symptoms of these painful attacks can be treated effectively with C1-INH concentrate. OBJECTIVE: to document the efficacy and safety of a weight-based dose of C1-INH concentrate in the treatment of successive HAE attacks at abdominal and facial locations. METHODS: acute facial and abdominal attacks were each treated with C1-INH concentrate using a single intravenous dose of 20 U/kg body weight. Efficacy end points included patient-reported time to onset of symptom relief and time to complete resolution of all symptoms. Safety was assessed by monitoring adverse events and assaying for markers of viral infection. RESULTS: we treated 663 abdominal attacks in 50 patients and 43 facial attacks in 16 patients (a total of 706 attacks in 53 patients). The median time to onset of relief for all attacks was 19.8 minutes, with a median time to complete resolution of 11.0 hours. The median time to onset of relief was 19.8 minutes for abdominal attacks and 28.2 minutes for facial attacks, indicating efficacy for both types of attack. No treatment-related serious adverse events occurred, and C1-INH concentrate was well tolerated. No human immunodeficiency virus, hepatitis virus, or parvovirus B19 infections arose during the study. CONCLUSION: the C1-INH concentrate dose of 20 U/kg provides rapid, effective, and safe treatment for successive HAE attacks at abdominal and facial locations.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Abdome , Doença Aguda , Adolescente , Adulto , Criança , Proteína Inibidora do Complemento C1/efeitos adversos , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Time to onset of symptom relief in hereditary angioedema (HAE) is a common primary end point in clinical studies but it has never been validated by correlation with the course of HAE symptoms. This study was designed as a retrospective validation of the primary end point for a placebo-controlled phase II/III study in patients with HAE. Ninety-eight abdominal attacks were treated with 10 or 20 U/kg of a highly purified C1 esterase inhibitor (C1-INH) concentrate or placebo. The primary end point was the time to onset of symptom relief, as determined by the patients. Patients assessed the intensity of the symptoms of pain, nausea, vomiting, cramps, and diarrhea over time. By Spearman rank correlation, the primary end point was compared with the time to first reduction of (1) any symptom intensity, (2) the sum of symptom intensity scores, and (3) the intensity of the last symptom present at baseline. The C1-INH, 20 U/kg, and placebo groups were compared by one-sided two-sample Wilcoxon tests. The time to first reduction in intensity of the last symptom present at baseline had the highest correlation with the primary end point (r = 0.77). The time to onset of symptom relief and the time to the first reduction in intensity of the last symptom were significantly shorter for the C1-INH, 20 U/kg, group compared with placebo (p = 0.009 and p = 0.0036, respectively). The association with the intensity of single symptoms confirmed that the time to onset of symptom relief is an appropriate end point for assessing the efficacy of C1-INH therapy.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Determinação de Ponto Final , Proteína Inibidora do Complemento C1/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hereditary angioedema (HAE) results from a genetic deficiency of C1-inhibitor. Two similar independent, randomized, saline controlled, double-blind studies were conducted to evaluate the efficacy and safety of recombinant human C1-inhibitor (rhC1INH) as a treatment of acute angioedema attacks in patients with HAE. OBJECTIVE: Analysis of pooled study results. METHODS: Patients with an eligible attack were randomized to a single intravenous dose of rhC1INH or saline. Efficacy was assessed by using patient-reported visual analog scale outcomes, and safety was assessed by using adverse events and immunogenicity of rhC1INH. RESULTS: rhC1INH at 100 (n = 29) and 50 (n = 12) U/kg body weight resulted in a significant reduction for both the primary endpoint time to the beginning of relief of symptoms compared with saline (n = 29): median, 66 (95% CI, 61-122) minutes, 122 (72-136) minutes, and 495 (245-520) minutes, P < .001 and P = .013, respectively; and for the secondary endpoint time to minimal symptoms, median, 266 (242-490) minutes, 247 (243-484) minutes, and 1210 (970-1500) minutes, P < .001 and P = .001, respectively. Therapeutic failure occurred in 59% (17/29) of the saline group compared with 0% (0/12) of the 50 U/kg group and 10% (3/29) of the 100 U/kg group. Treatment-emergent adverse events were unremarkable and tended to be reported more frequently in the saline group. No postexposure antibody responses against rhC1INH or host-related impurities were observed. CONCLUSION: Administration of rhC1INH at 100 or 50 U/kg was highly effective as a treatment of acute attacks in patients with HAE and appeared to be safe and well tolerated.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Doença Aguda , Angioedemas Hereditários/imunologia , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/imunologia , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Injeções Intravenosas , Masculino , América do Norte , Medição da Dor , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/imunologia , Resultado do TratamentoRESUMO
INTRODUCTION: Hereditary angioedema (HAE) is a rare disorder characterized by C1 esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema that can be life-threatening if they occur in the laryngeal region. We assessed the efficacy of C1-INH concentrate in the emergency treatment of rarely occurring acute laryngeal HAE attacks in a prospective, open-label clinical study. METHODS: Acute laryngeal attacks were each treated with C1-INH concentrate (Berinert) at a single dose of 20 U/kg body weight. Efficacy endpoints included time to onset of symptom relief and time to complete resolution of all symptoms, each based on the patient's assessment. RESULTS: All 39 laryngeal attacks in 16 patients were treated successfully. The median time to onset of symptom relief was 15 min. The median time to complete resolution of all symptoms was 8.25 h. No treatment-related serious adverse events occurred, and the treatment was well tolerated. The administration of C1-INH concentrate was not associated with any viral infections. CONCLUSION: C1-INH concentrate is an effective and safe emergency treatment for providing reliable and rapid relief from the potentially life-threatening symptoms of laryngeal HAE attacks.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/administração & dosagem , Doenças da Laringe/tratamento farmacológico , Adolescente , Adulto , Angioedemas Hereditários/genética , Angioedemas Hereditários/imunologia , Angioedemas Hereditários/fisiopatologia , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/genética , Intervalo Livre de Doença , Edema , Serviços Médicos de Emergência , Estudos de Viabilidade , Feminino , Humanos , Doenças da Laringe/genética , Doenças da Laringe/imunologia , Doenças da Laringe/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder. OBJECTIVE: To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema. METHODS: This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours. RESULTS: Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus. CONCLUSION: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The doctorate in nursing practice (DNP) degree is recommended as the terminal degree for advanced practice nurses by 2015. Improvement in the quality of palliative and end-of-life care for children with cancer is recognized as a health care priority. The purpose of this article is to describe: (a) how the American Association of Colleges of Nursing's 8 core elements and competencies can be used by DNP-advanced practice nurses in pediatric oncology settings and (b) the DNP-advanced practice nurses' leadership role to advocate translation of evidence in the care of pediatric oncology patients and to promote interdisciplinary collaboration to improve health care outcomes for pediatric oncology patients.
Assuntos
Prática Avançada de Enfermagem/normas , Competência Clínica/normas , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/normas , Enfermagem Oncológica/normas , Enfermagem Pediátrica/organização & administração , Sociedades de Enfermagem/normas , Assistência Terminal/normas , Adolescente , Adulto , Criança , Pré-Escolar , Educação de Pós-Graduação em Enfermagem/normas , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Estados Unidos , Adulto JovemRESUMO
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 UnidosRESUMO
Gastroesophageal reflux disease (GERD) is a major problem in primary care. More than 25% of the population experience GERD symptoms, and nonerosive forms of the disease are common. Conservative management is recommended. This review and case study presents conservative treatment options from the updated guidelines for the adult patient with GERD.
Assuntos
Refluxo Gastroesofágico/terapia , Adulto , Antiácidos/uso terapêutico , Antiulcerosos/uso terapêutico , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/etiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Avaliação em Enfermagem , Planejamento de Assistência ao Paciente , Exame Físico , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/métodos , Prognóstico , Fatores de RiscoRESUMO
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.