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1.
Pediatr Allergy Immunol ; 30(5): 562-568, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30993784

RESUMO

BACKGROUND: Attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (C1-INH-HAE) usually begin during childhood or adolescence. However, limited data are available regarding indications and modalities of treatment of children. This study evaluated recombinant human C1-INH (rhC1-INH) for HAE attacks in children. METHODS: This open-label, phase 2 study included children aged 2-13 years with C1-INH-HAE. Eligible HAE attacks were treated intravenously with rhC1-INH 50 IU/kg body weight (maximum, 4200 IU). The primary end-point was time to beginning of symptom relief (TOSR; ≥20 mm decrease from baseline in visual analog scale [VAS] score, persisting for two consecutive assessments); secondary end-point was time to minimal symptoms (TTMS; <20 mm VAS score for all anatomic locations). RESULTS: Twenty children (aged 5-14 years; 73 HAE attacks) were treated with rhC1-INH. Seventy (95.9%) of the attacks were treated with a single dose of rhC1-INH. Seven (35.0%) children were treated for four or more attacks. Overall, median TOSR was 60.0 minutes (95% confidence interval [CI], 60.0-65.0); data were consistent across attacks. Median TTMS was 122.5 minutes (95% CI, 120.0-126.0); data were consistent across attacks. No children withdrew from the study due to adverse events. No treatment-related serious adverse events or hypersensitivity reactions were reported; no neutralizing antibodies were detected. CONCLUSIONS: Recombinant human C1-INH was efficacious, safe, and well tolerated in children. Data support use of the same dosing regimen for HAE attacks in children (50 IU/kg; up to 4200 IU, followed by an additional dose, if needed) as is currently recommended for adolescents and adults.

2.
J Allergy Clin Immunol Pract ; 7(6): 1793-1802.e2, 2019.
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.

3.
J Pediatr ; 203: 204-209.e2, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30270168

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of a structured gradual exposure protocol (SGEP) with extensively heated and baked milk in promoting allergy resolution in children with cow milk allergy (CMA). STUDY DESIGN: In a case control study, children with CMA aged 1-4 years who were treated with SGEP including extensively heated and baked milk, were compared with children treated with strict avoidance. Data were collected from medical records and from validated telephone questionnaires. Data analysis was performed using a nonparametric Kaplan-Meier and proportional hazard Cox regression model, after evaluation of the adequacy of the case control matching. RESULTS: There were 43 children with milk allergy-26 (62%) males with a mean age at intervention of 21 months (range, 12-47 months)-who were treated with SGEP and followed to a mean age of 40 months (range, 20-82 months). The median age at resolution of CMA was compared with a matched group of 67 children treated with strict avoidance at least until 4 years of age or followed until earlier resolution, with a mean age at follow-up of 71 months (range, 11-176 months). The median estimated age at CMA resolution in the SGEP group was 36 months (95% CI, 34.5-49.7) compared with 98 months (95% CI, 82.4-114.1) in controls (P < .001). At last follow-up, 86% of treated children were tolerant to unheated milk proteins vs 52% of controls (P = .003). CONCLUSION: A structured protocol with extensively heated and baked milk seems to promote faster resolution of CMA.

4.
Isr Med Assoc J ; 20(4): 227-232, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29629730

RESUMO

BACKGROUND: Management of patients with hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is evolving worldwide. Evaluating the Israeli experience may provide valuable insights. OBJECTIVES: To compare demographics and icatibant treatment patterns and outcomes in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey (IOS) in Israel with those in other countries. METHODS: The IOS is an ongoing observational study that prospectively monitors real-world icatibant safety/tolerability and treatment outcomes. RESULTS: By July 2016, 58 patients from Israel and 594 patients from other countries were enrolled. Median age at diagnosis (16.7 vs. 21.3 years, P = 0.036) and median delay between symptom onset and diagnosis (0.8 vs. 6.6 years, P = 0.025) were lower in Israel compared with other countries, respectively. Differences in attack severity were not significant (P = 0.156); however, during follow-up, Israeli patients were less likely to miss > 7 days of work/school due to C1-INH-HAE-related complications (P = 0.007). A trend was also shown in Israel for earlier time to treatment (median 0.5 vs. 1.3 hours, P = 0.076), attack duration was shorter (median 5.0 vs. 9.0 hours, P = 0.026), and patients more often self-administered icatibant (97.2% vs. 87.5%, P = 0.003), respectively. However, Israeli patients were less likely to treat attacks (P = 0.036). Whereas patients in Israel reported exclusive use of danazol for long-term prophylaxis, those in other countries used various agents, including C1-INH. CONCLUSIONS: Recognition of C1-INH-HAE and timeliness of icatibant treatment appear more favorable, and attack duration shorter, in Israel compared with other countries.

5.
Allergy Asthma Proc ; 38(6): 456-461, 2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-28874235

RESUMO

BACKGROUND: Severe attacks of hereditary angioedema (HAE) are debilitating and potentially life threatening, and can increase anxiety and the use of medical resources. OBJECTIVE: This post hoc assessment evaluated recombinant human C1 esterase inhibitor (rhC1-INH) used to treat acute severe HAE attacks. METHODS: In a double-blind, randomized-controlled trial (RCT), patients with an HAE attack (baseline visual analog scale score of ≥50 mm, with severe attacks defined as ≥75 mm) were randomly assigned to receive rhC1-INH (50 IU/kg for patients who weighed <84 kg; 4200 IU for patients who weighed ≥84 kg) or placebo. Also, in an open-label extension (OLE) study of rhC1-INH, oropharyngeal-laryngeal attacks were analyzed. Rescue therapy with rhC1-INH 50 IU/kg (≤4200 IU) was permitted after 4 hours or for life-threatening symptoms (in the RCT) or after 1 hour (in the OLE study). The primary end point measured the time to the beginning of symptom relief by using the Treatment Effects Questionnaire. RESULTS: Of 75 adults in the RCT, 43 had severe attacks and received either rhC1-INH (n = 24) or placebo (n = 19). The median (95% confidence interval) time to the onset of symptom relief totaled 90.0 minutes (95% confidence interval, 47.0-120.0 minutes) versus 334.0 minutes (95% confidence interval, 105.0 to not calculable minutes; hazard ratio, 2.5; p = 0.02), for rhC1-INH and placebo, respectively. Open-label rhC1-INH rescue therapy was administered to 1 of 24 in the rhC1-INH group (4.2%) and 10 of 19 in the placebo group (52.6%). During the OLE study, the median onset of symptom relief with rhC1-INH for eight oropharyngeal-laryngeal HAE attacks was 69.0 minutes (95% confidence interval, 59.0-91.0 minutes). CONCLUSION: In the current study, rhC1-INH was efficacious in resolving severe HAE attacks, including oropharyngeal-laryngeal attacks. The rhC1-INH rescue treatment rapidly improved symptoms for patients who received placebo and who experienced worsening or sustained symptoms.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Lancet ; 390(10102): 1595-1602, 2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28754491

RESUMO

BACKGROUND: Hereditary angio-oedema is a recurrent, oedematous disorder caused by deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect of recombinant human C1 esterase inhibitor has not been rigorously studied. We aimed to assess the efficacy of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema. METHODS: We conducted this phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial at ten centres in Canada, the Czech Republic, Israel, Italy, Macedonia, Romania, Serbia, and the USA. We enrolled patients aged 13 years or older with functional C1-inhibitor concentrations of less than 50% of normal and a history of four or more attacks of hereditary angio-oedema per month for at least 3 months before study initiation. Patients were randomly assigned centrally (1:1:1:1:1:1), via an interactive response technology system with fixed allocation, to receive one of six treatment sequences. During each sequence, patients received intravenous recombinant human C1 esterase inhibitor (50 IU/kg; maximum 4200 IU) twice weekly, recombinant human C1 esterase inhibitor once weekly and placebo once weekly, and placebo twice weekly, each for 4 weeks with a 1 week washout period between crossover. All patients, investigators, and study personnel who participated in patient care were masked to group allocation during the study. The primary efficacy endpoint was the number of attacks of hereditary angio-oedema observed in each 4 week treatment period. Attack symptoms were recorded daily. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one injection of study medication. This study is registered with ClinicalTrials.gov, number NCT02247739. FINDINGS: Between Dec 29, 2014, and May 3, 2016, we enrolled 35 patients, of whom 32 (91%) underwent randomisation (intention-to-treat population) and 26 (81%) completed the study. The mean number of attacks of hereditary angio-oedema over 4 weeks was significantly reduced with recombinant human C1 esterase inhibitor twice weekly (2·7 attacks [SD 2·4]) and once weekly (4·4 attacks [3·2]) versus placebo (7·2 attacks [3·6]), with mean differences of -4·4 attacks (p<0·0001) and -2·8 attacks (p=0·0004), respectively. We recorded adverse events in ten (34%) of 29 patients given twice-weekly recombinant human C1 esterase inhibitor, 13 (45%) of 29 patients given the once-weekly regimen, and eight (29%) of 28 patients given placebo. Headache (twice-weekly treatment) and nasopharyngitis (once-weekly treatment) were the most common adverse events. Two (7%) adverse events (fatigue and headache) were deemed possibly related to treatment with recombinant human C1 esterase inhibitor, but both resolved without additional treatment. No thrombotic or thromboembolic events, systemic allergic reactions (including anaphylaxis), or neutralising antibodies were reported. INTERPRETATION: Prophylaxis with recombinant human C1 esterase inhibitor provided clinically relevant reductions in frequency of hereditary angio-oedema attacks and was well tolerated. In view of the pharmacokinetic profile of recombinant human C1 esterase inhibitor, our results suggest that efficacy of C1-inhibitor replacement therapy might not be a direct function of plasma trough concentrations of C1 inhibitor. FUNDING: Pharming Technologies.


Assuntos
Angioedemas Hereditários/prevenção & controle , Proteína Inibidora do Complemento C1/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Adolescente , Adulto , Idoso , Angioedemas Hereditários/sangue , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/farmacocinética , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Resultado do Tratamento , Adulto Jovem
7.
J Allergy Clin Immunol Pract ; 5(6): 1671-1678.e2, 2017 Nov - Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28601641

RESUMO

BACKGROUND: Clinical manifestations of hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) usually begin in childhood, often intensifying during puberty. Currently there are insufficient efficacy/safety data for HAE therapies in children and adolescents due to the small number of pediatric patients enrolled in studies. OBJECTIVE: The objective of this phase 3 study was to evaluate the efficacy/safety of a single subcutaneous dose of icatibant (0.4 mg/kg; maximum 30 mg) in pediatric patients with C1-INH-HAE. METHODS: Patients aged 2 years to younger than 18 years were categorized as prepubertal (children) and pubertal/postpubertal (adolescents). The primary end point was time to onset of symptom relief-earliest time posttreatment to 20% or more improvement in composite symptom score. RESULTS: Thirty-two patients received icatibant (safety population: 11 children with attack, 10 adolescents without attack, and 11 adolescents with attack). The efficacy population consisted of 11 children and 11 adolescents with edematous attacks. Most attacks in the efficacy population (16 [72.7%]) were cutaneous, 5 (22.7%) were abdominal, and 1 (4.5%) was both cutaneous and abdominal; none was laryngeal. Overall, the median time to onset of symptom relief was 1.0 hour, the same for children and adolescents. Thirty-two treatment-emergent adverse events (all mild or moderate) occurred in 9 (28.1%) patients. Gastrointestinal symptoms were most common (9 events in 3 [9.4%] patients). Injection-site reactions affected most (90.6%) patients (particularly erythema and swelling), but almost all resolved by 6 hours postdose. Icatibant demonstrated a monophasic plasma concentration-time profile. Time to peak concentration was approximately 0.5 hours postdose. CONCLUSIONS: Symptom relief was rapid, and a single icatibant injection in pediatric patients with C1-INH-HAE was well tolerated (ClinicalTrials.gov identifier, NCT01386658).


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/uso terapêutico , Bradicinina/análogos & derivados , Proteína Inibidora do Complemento C1/genética , Adolescente , Asfixia , Bradicinina/uso terapêutico , Criança , Pré-Escolar , Proteína Inibidora do Complemento C1/metabolismo , Feminino , Humanos , Injeções Subcutâneas , Masculino , Puberdade , Resultado do Tratamento
8.
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.
J Allergy Clin Immunol Pract ; 5(4): 1091-1097, 2017 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28202404

RESUMO

BACKGROUND: Recombinant human C1-esterase inhibitor (rhC1-INH) is efficacious and well tolerated for managing hereditary angioedema (HAE) attacks in adults. However, there are insufficient data on its efficacy and safety in adolescents. OBJECTIVE: To evaluate the efficacy and safety profiles of rhC1-INH for acute HAE attacks in adolescents. METHODS: Adolescents (aged 12-18 y) with HAE enrolled in 2 randomized controlled trials and 2 open-label extension trials were included and received intravenous rhC1-INH for acute attacks. Times to the beginning of sustained symptom relief (visual analog scale change from baseline ≥20 mm) and minimal symptoms (visual analog scale score of <20 mm across locations) were assessed. Safety parameters included hypersensitivity reactions, anti-rhC1-INH antibodies, and host-related impurities. RESULTS: Sixteen adolescents (50 attacks, aged 14-18 y) received rhC1-INH. Attacks were managed with single-dose rhC1-INH 50 U/kg (46.0%) and single-dose rhC1-INH 2100 U (16%), and 32.0% were treated with additional doses after receiving an initial rhC1-INH 2100 U dose (total dose, 4200-6300 U). Most attacks (88.0%) occurred at a single location; 59.1% (26 of 44) were abdominal. Across the first 5 attacks, median times to the beginning of symptom relief ranged from 19.0 to 78.5 minutes; median times to minimal symptoms ranged from 120 to 190 minutes. Pharmacokinetics showed that rhC1-INH restored functional plasma C1-esterase inhibitor levels to the normal (>70%) range for almost all evaluable patients. No severe or drug-related adverse events or hypersensitivity reactions occurred. No treatment-emergent antibodies to rhC1-INH or host-related impurities were observed. CONCLUSIONS: rhC1-INH is efficacious and well tolerated among adolescents with HAE.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Adolescente , Proteína Inibidora do Complemento C1/análise , Proteína Inibidora do Complemento C1/farmacocinética , Método Duplo-Cego , Feminino , Humanos , Masculino , Resultado do Tratamento
10.
Clin Rev Allergy Immunol ; 51(2): 121-39, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27287037

RESUMO

The term "swelling" has been used in the old scriptures to illustrate a change of normal figure and, as such, an expression of illness. It should be noted that in ancient times, human diseases were very often regarded a punishment from God. Hence, it is not surprising that one of the oldest tests for infidelity involved swelling as an inflicted punishment. The great Greek physician Hippocrates (377-460 BC), considered one of the most outstanding figures in the history of medicine and "Father of the Western Medicine," already used the term oídema to describe swelling of organs. It took many centuries later until the first description of angioedema as a distinct medical entity was minted by Quinke in 1882. The historical progression in angioedema research has been characterized by intermittent "leaps" in interest and scientific achievements. As an example, it took 75 years from the accurate description of hereditary angioedema (HAE) by Osler (1888), until a group of researchers headed by Donaldson (1963) disclosed the central role of C1 inhibitor in angioedema pathophysiology. What followed was a result of a collective effort by many researchers and scientific groups who were able to elucidate the intricate connections between the implicated biochemical pathways. Still, scientific progress was hardly translated into effective therapy, and another 45 years had to elapse until the renewed interest in HAE was boosted by studies on the efficacy and safety of novel therapies about 10 years ago. In the twenty-first century, HAE ceased to be an "orphan disease" and its future is far more optimistic. It is better managed now by specialized angioedema centers, harmonized clinical guidelines, educational programs, laboratory services, and continued basic and clinical research. Patient associations worldwide are offering support and guidance, and governments and healthcare systems are gradually addressing patient and family needs.


Assuntos
Angioedema/etiologia , Bradicinina/metabolismo , Angioedema/diagnóstico , Angioedema/história , Angioedema/terapia , Animais , Terapia Combinada , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Proteína Inibidora do Complemento C1/uso terapêutico , Fibrinólise , Predisposição Genética para Doença , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , Humanos , Receptores da Bradicinina/metabolismo , Resultado do Tratamento
11.
J Allergy Clin Immunol Pract ; 4(3): 464-473.e4, 2016 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26969268

RESUMO

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) may affect health-related quality of life (HRQoL). A specific HRQoL questionnaire for adult patients with C1-INH-HAE, the HAE-QoL, has recently been developed in Spain. OBJECTIVE: The objective of this study was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. METHODS: Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. RESULTS: Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft version of the HAE-QoL was pilot tested in 332 patients, and accurate data were obtained from 290 patients from 11 countries. The reduction process resulted in a new version with 25 items and 7 dimensions (treatment difficulties, physical functioning and health, disease-related stigma, emotional role and social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0.45 and 0.64, respectively) and with SF-36v2 dimensions (P < .004). HAE-QoL scores discriminated significantly among severity groups (median: asymptomatic 133.5 vs severe 84.0; P < .001); between patients with and without long-term prophylaxis (median: 101 vs 90; P = .001); and between patients with and without psychiatric and/or psychological care (median: 74 vs 103; P ≤ .001). CONCLUSIONS: The HAE-QoL, currently available in 18 languages, showed good reliability and validity evidence.


Assuntos
Angioedemas Hereditários/psicologia , Qualidade de Vida , Inquéritos e Questionários , Adulto , Feminino , Humanos , Masculino , Psicometria
13.
Ann Allergy Asthma Immunol ; 116(4): 329-33, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26922211

RESUMO

BACKGROUND: Drug provocation tests (DPTs) are the gold standard in the diagnosis of ß-lactam hypersensitivity. However, no consensus exists on the need for extended provocation tests, even though the effectiveness of the short DPT is relatively low and there has been an increase in the relative incidence of nonimmediate hypersensitivity reactions. OBJECTIVE: To evaluate the effectiveness of a 7-day (extended) DPT compared with a 1-day-only (short) DPT in the management of hypersensitivity reactions to ß-lactam antibiotics. METHODS: Patients referred to the allergy clinic of the Sheba Medical Center for suspected ß-lactam hypersensitivity from January 2008 to December 2012 underwent in vivo skin tests and an immediate short DPT with the culprit drug. Unless an immediate reaction was clearly documented, patients were offered a 7-day, extended DPT. Long-term effectiveness, calculated as the subsequent use of the tested antibiotic, and satisfaction levels were assessed with a telephone questionnaire. RESULTS: Of 49 negative DPT results, 26 (53%) were long and 23 (47%) were short. A total of 78% of the patients who underwent the long DPT reported that they used the drug compared with 61% of those who underwent only the short DPT (P = .049). Most patients were very satisfied with the drug allergy evaluation process. CONCLUSIONS: An extended DPT protocol increased the effectiveness of the allergy workup in our center without compromising patient satisfaction and safety, and it should be recommended to patients with a history of nonimmediate reaction to ß-lactam.


Assuntos
Hipersensibilidade a Drogas/diagnóstico , Fatores de Tempo , beta-Lactamas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Hipersensibilidade a Drogas/complicações , Feminino , Humanos , Imunização/métodos , Lactente , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , Adulto Jovem , beta-Lactamas/efeitos adversos
14.
Isr Med Assoc J ; 18(8): 493-494, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28471584
15.
J Allergy Clin Immunol Pract ; 3(3): 417-23, 2015 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25680925

RESUMO

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 Unidos
16.
Ann Allergy Asthma Immunol ; 112(2): 163-169.e1, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24468257

RESUMO

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 Jovem
20.
Allergy Asthma Proc ; 34(3): 261-6, 2013 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23676575

RESUMO

In patients with hereditary angioedema (HAE), premonitory symptoms ("prodromes") may appear hours to days before attack onset. It remains to be determined if prodromes could be useful indicators for early treatment initiation. Most published reports of prodromes have been limited to case reports or small case series. The common objective of several recent survey-based studies was to collect information relevant to prodromal patterns in patients with HAE. Three separate surveys solicited prodromal data from HAE patients. Although differences in survey methodologies permit only descriptive analysis of data, responses to the surveys provide the largest compilation of observational data on this topic to date. Prodromes were reported by 82.5-95.7% of patients surveyed. In one survey, about two-thirds of subjects reported experiencing prodromes before all or most acute HAE attacks, and only 6% of subjects noted the appearance of prodromes in <10% of all attacks. The most common types of prodromal symptoms were related to skin/soft tissue and gastrointestinal tract. Most prodromes were experienced hours to days before the onset of angioedema. A large percentage of surveyed subjects indicated being able to predict an impending HAE attack all or most of the time; <10% reported being rarely or never able to predict an attack. Although insufficient to establish the clinical role of prodromal symptoms, results of these surveys provide additional data on the scope of prodromes and could stimulate further research into the potential efficacy and cost-effectiveness of HAE attack prediction and prodrome-triggered interventions.


Assuntos
Angioedemas Hereditários/diagnóstico , Sintomas Prodrômicos , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
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