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1.
Clin Toxicol (Phila) ; 57(3): 164-167, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30260274

RESUMO

CONTEXT: The administration of Crotalidae polyvalent immune Fab (FabAV) currently requires close observation, so patients can be monitored for hypersensitivity reactions. The objective of this study was to evaluate the occurrence of hypersensitivity reactions to FabAV. METHOD: This was a retrospective cohort study utilizing data from a statewide poison center database in the United States. Records of all patients envenomated by a rattlesnake and treated with FabAV between January 2002 and December 2014 were evaluated. Patients with acute hypersensitivity reactions were identified, and reactions were evaluated descriptively. RESULTS: A total of 1340 adult and pediatric patients received FabAV during the study period. Of these, 19 (1.4%) patients had a potential reaction to FabAV, with 10 requiring a reduction in infusion rate, but none requiring discontinuation of the antivenom. Reactions occurred during the loading dose (n = 10), maintenance doses (n = 4), or were delayed reactions (n = 6). Symptoms recorded included pruritus (n = 8), hives (n = 8), rash (n = 7), vomiting (n = 7), nausea (n = 6), dyspnea or wheezing (n = 4), diaphoresis (n = 3), throat irritation (n = 2), and mild hypotension (n = 2). One patient was given a concomitant administration of low dose epinephrine infusion until completion of the antivenom course. However, none of the reactions were considered to be life-threatening. CONCLUSION: FabAV appears to be associated with a low incidence of acute hypersensitivity reactions. Patients may not require placement in a location capable of detecting and rapidly responding to hemodynamic and/or airway issues for FabAV monitoring alone.


Assuntos
Antivenenos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fatores Imunológicos/efeitos adversos , Adulto , Idoso , Antivenenos/uso terapêutico , Estudos de Coortes , Venenos de Crotalídeos/imunologia , Bases de Dados Factuais , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Estudos Retrospectivos , Mordeduras de Serpentes/tratamento farmacológico , Resultado do Tratamento , Estados Unidos/epidemiologia
2.
South Med J ; 111(12): 716-720, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30512122

RESUMO

OBJECTIVE: To compare the incidence of hypersensitivity reactions following copperhead envenomation treated with Fab antivenom (FabAV) or placebo. METHODS: Patients with copperhead snakebites received treatment and follow-up in a prospective, randomized, double-blind, placebo-controlled trial of FabAV or placebo. The treatment allocation ratio was 2:1 (FabAV:placebo). All of the included patients received at least one dose of study treatment. We reviewed all treatment-emergent adverse events (AEs) using a previously published scale to classify likely hypersensitivity reactions as mild, moderate, or severe. RESULTS: We enrolled 74 patients at 13 sites. Forty-five patients received FabAV, and 29 patients received placebo. Five FabAV patients and 4 placebo patients had moderate envenomations; the rest were mild. Twenty-five FabAV patients and 8 placebo patients had at least 1 AE. Mild skin reactions occurred in 11 (24%) FabAV patients (pruritis, urticaria, rash, ecchymosis, erythema) and 1 (3%) placebo patient (pruritis). Moderate gastrointestinal AEs occurred in 7 (16%) FabAV patients (nausea, vomiting, constipation, diarrhea, oral paresthesia) and in 2 (7%) placebo patients (nausea). Respiratory AEs occurred in 3 (7%) FabAV patients (dyspnea, pulmonary embolism, nasal congestion, sneezing) and no placebo patients. Hypotension occurred in 1 patient in each group. CONCLUSIONS: In a randomized controlled trial of FabAV for copperhead bites, the incidence of hypersensitivity reactions was low. Most reactions were mild skin reactions.


Assuntos
Agkistrodon , Antivenenos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antivenenos/uso terapêutico , Criança , Método Duplo-Cego , Hipersensibilidade a Drogas/epidemiologia , Feminino , Seguimentos , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
3.
JAMA Ophthalmol ; 136(6): 666-677, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29801123

RESUMO

Importance: Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials. Objective: To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA. Design, Setting, and Participants: Two identically designed phase 3 double-masked, randomized, sham-controlled clinical trials, Chroma and Spectri, enrolled participants from August 28, 2014, to October 6, 2016, at 275 sites in 23 countries. Participants were aged 50 years or older, with bilateral GA and no prior or active choroidal neovascularization in either eye and GA lesions in the study eye measuring 2.54 to 17.78 mm2 with diffuse or banded fundus autofluorescence patterns. Interventions: Participants were randomized 2:1:2:1 to receive 10 mg of intravitreous lampalizumab every 4 weeks, sham procedure every 4 weeks, 10 mg of lampalizumab every 6 weeks, or sham procedure every 6 weeks, through 96 weeks. Main Outcomes and Measures: Safety and efficacy assessed as mean change from baseline in GA lesion area at week 48 from centrally read fundus autofluorescence images of the lampalizumab arms vs pooled sham arms, in the intent-to-treat population and by complement factor I-profile genetic biomarker. Results: A total of 906 participants (553 women and 353 men; mean [SD] age, 78.1 [8.1] years) were enrolled in Chroma and 975 participants (578 women and 397 men; mean [SD] age, 77.9 [8.1] years) were enrolled in Spectri; 1733 of the 1881 participants (92.1%) completed the studies through 48 weeks. The adjusted mean increases in GA lesion area from baseline at week 48 were 1.93 to 2.09 mm2 across all groups in both studies. Differences in adjusted mean change in GA lesion area (lampalizumab minus sham) were -0.02 mm2 (95% CI, -0.21 to 0.16 mm2; P = .80) for lampalizumab every 4 weeks in Chroma, 0.16 mm2 (95% CI, 0.00-0.31 mm2; P = .048) for lampalizumab every 4 weeks in Spectri, 0.05 mm2 (95% CI, -0.13 to 0.24 mm2; P = .59) for lampalizumab every 6 weeks in Chroma, and 0.09 mm2 (95% CI, -0.07 to 0.24 mm2; P = .27) for lampalizumab every 6 weeks in Spectri. No benefit of lampalizumab was observed across prespecified subgroups, including by complement factor I-profile biomarker. Endophthalmitis occurred after 5 of 12 447 injections (0.04%) or in 5 of 1252 treated participants (0.4%) through week 48. Conclusions and Relevance: In Chroma and Spectri, the largest studies of GA conducted to date, lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment. Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2 mm2 per year. Trial Registration: ClinicalTrials.gov Identifier: NCT02247479 and NCT02247531.


Assuntos
Atrofia Geográfica/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Degeneração Macular/complicações , Idoso , Idoso de 80 Anos ou mais , Fator D do Complemento/antagonistas & inibidores , Método Duplo-Cego , Feminino , Angiofluoresceinografia , Atrofia Geográfica/diagnóstico , Atrofia Geográfica/etiologia , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Acuidade Visual
4.
Clin Toxicol (Phila) ; 56(11): 1115-1120, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29688079

RESUMO

Background: Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom. Methods: The American College of Medical Toxicology's Toxicology Investigators Consortium maintains a prospective case registry of poisoned and envenomated patients managed by medical toxicologists at the bedside. This registry includes the North American Snakebite sub-registry. We performed a review of 438 cases entered into the Snakebite sub-registry. Results: A total of 373 (85.2%) received at least one vial of Fab Antivenom. Forty percent were children. Adverse events occurred in 10 patients (2.7%) of whom six were adults. Rash was the most common adverse event. More severe adverse events (hypotension, bronchospasm, and/or angioedema) occurred in four (1.1%) patients. Prophylaxis was administered prior to Fab antivenom in 4.0%. Eight patients received various treatments for their adverse events. Neither the initial number of Fab antivenom vials, atopic history, nor prior envenomation correlated with the prevalence of adverse events. Discussion: This prevalence of adverse events was lower than in previous studies and in a meta-analysis of 11 studies. The types of adverse events and treatments used are consistent with those in previous reports. There were no prior reports of prophylaxis use with which to compare. Conclusion: The prevalence of Fab antivenom adverse events in the North American Snakebite Registry was 2.7%.


Assuntos
Antivenenos/efeitos adversos , Antivenenos/uso terapêutico , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Viperidae , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , América do Norte , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento , Estados Unidos , Adulto Jovem
5.
J Cyst Fibros ; 17(4): 484-491, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29292092

RESUMO

BACKGROUND: Chronic Pseudomonas aeruginosa (Pa) airways infection, exuberant local inflammation, and progressive lung function loss are hallmarks of cystic fibrosis (CF). KB001-A is an anti-PcrV PEGylated monoclonal antibody fragment to the Type III secretion system of Pa. This 16-week study evaluated KB001-A associated effect on time-to-need for antibiotics for worsening respiratory signs and symptoms, as well as safety, and treatment-associated changes in symptom scores, inflammatory markers, and spirometry. METHODS: This was a randomized, double-blind, placebo-controlled, repeat-dose study in CF subjects with Pa. Intravenous 10mg/kg KB001-A or placebo infusions were administered at baseline and weeks 2, 4, 8, and 16, with a 4-week follow-up. Sputum inflammatory markers were assessed in a sub-study. Time-to-need for antibiotics was compared between groups by Kaplan Meier analysis and Cox proportional hazards modeling adjusting for randomization strata. RESULTS: Of 182 subjects, 169 received at least one infusion of KB001-A (n=83) or placebo (n=86). KB001-A was generally safe and well-tolerated as compared to placebo, with no significant emergent adverse effects other than one serious adverse event of elevated hepatic enzymes of unclear etiology. Time to need for antibiotics did not differ between groups (HR: 1.00; 95% CI: 0.69, 1.45, p=0.995). A 3.2 increase in ppFEV1 from placebo favoring KB001-A was observed at week 16 (95% CI: 1.12, 5.30, p=0.003). Mean changes from baseline in log10 sputum neutrophil elastase (NE) had a non-significant decrease (-0.27, 95% CI: -0.58,0.04, p=0.084) while IL-8 concentrations at week 16 were significantly lower (-0.27, 95% CI: -0.55,0.00, p=0.048) among KB001-A subjects (n=16) relative to placebo (n=13). CONCLUSIONS: KB001-A was safe and well-tolerated and associated with a modest FEV1 benefit and reduction in select sputum inflammatory markers (IL-8). KB001-A was not associated with an increased time to need for antibiotics. The lack of efficacy seen with KB001-A may be due, in part, to the low levels of the type III secretion proteins previously reported in sputum of CF patients chronically infected with Pa.


Assuntos
Anticorpos Monoclonais , Fibrose Cística , Fragmentos Fab das Imunoglobulinas , Infecções por Pseudomonas , Testes de Função Respiratória/métodos , Escarro , Administração Intravenosa , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Fibrose Cística/microbiologia , Fibrose Cística/fisiopatologia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/fisiopatologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Escarro/metabolismo , Escarro/microbiologia , Resultado do Tratamento
6.
Cytokine ; 101: 56-63, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27567553

RESUMO

Tumor necrosis factor (TNF)-α is a potent pro-inflammatory and pathological cytokines in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases. Anti-TNF-α therapy has been established as an efficacious therapeutic strategy in these diseases. In clinical settings, three monoclonal anti-TNF-α full IgG1 antibodies infliximab, adalimumab, and golimumab, PEGylated Fab' fragment of anti-TNF-α antibody certolizumab pegol, extracellular domain of TNF receptor 2/IgG1-Fc fusion protein etanercept, are almost equally effective for rheumatoid arthritis. Although monoclonal full IgG1 antibodies are able to induce clinical and endoscopic remission in inflammatory bowel diseases, certolizumab pegol without Fc portion has been shown to be less effective for inflammatory bowel diseases compared to full IgG1 antibodies. In addition, there are no evidences that etanercept leads clinical remission in inflammatory bowel diseases. Besides the common effect of anti-TNF-α agents on neutralization of soluble TNF-α, each anti-TNF-α agent has its own distinctive pharmacological properties which cause the difference in clinical efficacies. Here we focus on the distinctions of action of anti-TNF-α agents especially in following points; (1) blocking ability against ligands, transmembrane TNF-α and lymphotoxin, (2) effects toward transmembrane TNF-α-expressing cells, (3) effects toward Fcγ receptor-expressing cells, (4) degradation and distribution in inflamed tissue. Accumulating evidence will give us the idea how to modify anti-TNF-α agents to enhance the clinical efficacy in inflammatory diseases.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/genética , Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/efeitos adversos , Adalimumab/genética , Adalimumab/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Certolizumab Pegol/efeitos adversos , Certolizumab Pegol/genética , Certolizumab Pegol/uso terapêutico , Modelos Animais de Doenças , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/genética , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoglobulina G/efeitos adversos , Imunoglobulina G/genética , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/genética , Fatores Imunológicos/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/imunologia , Infliximab/efeitos adversos , Infliximab/genética , Infliximab/uso terapêutico , Camundongos , Polietilenoglicóis/uso terapêutico , Fator de Necrose Tumoral alfa/imunologia
7.
BMC Cardiovasc Disord ; 17(1): 212, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28764639

RESUMO

BACKGROUND: Thrombolysis is still used when primary angioplasty is delayed for a long time, but 25%-30% of patients require rescue angioplasty (RA). There are no established recommendations for antithrombotic management in RA. This registry analyzes regimens for antithrombotic management. METHODS: A retrospective, multicenter, observational registry of consecutive patients treated with RA at 8 hospitals. All variables were collected and follow-up took place at 6 months. RESULTS: The study included 417 patients. Antithrombotic therapy in RA was: no additional drugs 22.3%, unfractionated heparin (UFH) 36.6%, abciximab 15.5%, abciximab plus UFH 10.5%, bivalirudin 5.7%, enoxaparin 4.3%, and others 4.7%. Outcomes at 6 months were: mortality 9.1%, infarction 3.3%, definite or probable stent thrombosis 4.3%, revascularization 1.9%, and stroke 0.5%. Mortality was related to cardiogenic shock, age > 75 years, and anterior location. The stent thrombosis rate was highest with bivalirudin (12.5% at 6 months). The incidence of bleeding at admission was high (14.8%), but most cases were not severe (82% BARC ≤2). Variables independently associated with bleeding were: femoral access (OR 3.30; 95% CI 1.3-8.3: p = 0.004) and post-RA abciximab infusion (OR 2.26; 95% CI 1.02-5: p = 0.04). CONCLUSIONS: Antithrombotic treatment regimens in RA vary greatly, predominant strategies consisting of no additional drugs or UFH 70 U/kg. No regimen proved predictive of mortality, but bivalirudin was related to more stent thrombosis. There was a high incidence of bleeding, associated with post-RA abciximab infusion and femoral access.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Enoxaparina/administração & dosagem , Fibrinolíticos/administração & dosagem , Hirudinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Infarto do Miocárdio/terapia , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Terapia Trombolítica , Abciximab , Idoso , Anticorpos Monoclonais/efeitos adversos , Distribuição de Qui-Quadrado , Trombose Coronária/etiologia , Esquema de Medicação , Enoxaparina/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hirudinas/efeitos adversos , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Razão de Chances , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Falha de Tratamento
8.
BMJ Case Rep ; 20172017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28710245

RESUMO

Abciximab (c7E3 Fab) is one of the three potent intravenous glycoprotein IIb/IIIa receptor inhibitors (along with eptifibatide and tirofiban) that have shown significant positive outcomes when used in patients with intracoronary thrombus. However, major side effects have been reported with its use including hypotension, major bleeding and thrombocytopenia. This case is a 53-year-old man presenting with acute chest pain diagnosed with non-ST-elevation myocardial infarction, who underwent percutaneous coronary intervention with abciximab and heparin infusion and developed acute profound thrombocytopenia (platelet count <20,000/L) within 9 hours of infusion. This case demonstrates the importance of routinely monitoring the platelet count prior to and 2-4 hours following abciximab infusion and differentiating other causes of acute profound thrombocytopenia, particularly pseudothrombocytopenia and heparin-induced thrombocytopenia.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Infarto do Miocárdio/terapia , Inibidores da Agregação de Plaquetas/efeitos adversos , Trombocitopenia/diagnóstico , Abciximab , Angioplastia , Dor no Peito/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente
9.
BMJ Case Rep ; 20172017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28576909

RESUMO

Abciximab, the first approved glycoprotein (GP IIb/IIIa) inhibitor, is being widely used during acute coronary syndromes and offers the promising approach to antithrombotic therapy. We present a case of a young woman who initially received abciximab infusion for undergoing percutaneous coronary intervention of left anterior descending artery and was eventually diagnosed with abciximab-induced delayed thrombocytopaenia. This case outlines the importance of close follow-up of these patients to prevent serious adverse events.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Abciximab , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Doença da Artéria Coronariana/cirurgia , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Infusões Intravenosas , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Resultado do Tratamento , Adulto Jovem
10.
Clin Toxicol (Phila) ; 55(7): 668-669, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28443380

RESUMO

Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the treatment of clinically significant North American crotalinae envenomation, is generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody response to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) has been established following red-meat consumption as well as IV administration of cetuximab, which contain the α-gal epitope. We present a case of α-gal allergy discovered after acute hypersensitivity reaction to FabAV. A 61-year-old healthy female was bitten on her left ankle by Agkistrodon contortrix. Given the patient's rapid progression of pain and swelling, she was given FabAV. During infusion of FabAV, she developed diffuse hives over her entire body and itching, but denied respiratory or gastrointestinal symptoms and her vital signs remained stable. The FabAV was immediately discontinued and she received intravenous diphenhydramine and famotidine with gradual resolution of symptoms. On further discussion, she denied a history of α-gal or papaya allergy but rarely ate red meat and endorsed sustaining frequent tick bites. Subsequent antibody testing was significant for an α-1,3-galactose IgE concentration of 45,000 U/L (normal <3500 U/L), confirming α-gal allergy. To our knowledge, this is the first report of FabAV hypersensitivity associated with an underlying α-gal allergy.


Assuntos
Agkistrodon/imunologia , Antivenenos/efeitos adversos , Venenos de Crotalídeos/imunologia , Dissacarídeos/imunologia , Hipersensibilidade a Drogas/etiologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Mordeduras de Serpentes/tratamento farmacológico , Picadas de Carrapatos/imunologia , Urticária/induzido quimicamente , Animais , Antialérgicos/administração & dosagem , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Testes Imunológicos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Mordeduras de Serpentes/diagnóstico , Mordeduras de Serpentes/imunologia , Resultado do Tratamento , Urticária/diagnóstico , Urticária/tratamento farmacológico , Urticária/imunologia
11.
Expert Rev Vaccines ; 16(3): 273-287, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27809689

RESUMO

INTRODUCTION: Rabies is a worldwide zoonotic viral disease with no specific treatment once symptoms occur; manifest disease is almost always fatal. WHO recommendations for exposed individuals include immediate attention to the wound and use of rabies immunoglobulin and/or vaccine for post-exposure prophylaxis (PEP). Here, we provide an overview of the clinical experience with a highly purified preparation of F(ab')2 fragments from equine rabies immunoglobulin (F(ab')2 pERIG; FavirabTM) in rabies PEP. Areas covered: Our review comprises a retrospective analysis of adverse event reports in the Sanofi Pasteur global pharmacovigilance database for F(ab')2 pERIG, including adverse event reports from eight Sanofi Pasteur-sponsored clinical trials and post-market surveillance data collected between 1995 and 2014. The general safety profile of F(ab')2 pERIG is discussed, as are the occurrence of rare anaphylactic reactions, and suspected intervention failure. Expert commentary: Over 20 years of clinical development and post-licensure experience has established the safety and effectiveness of F(ab')2 pERIG (FavirabTM) in rabies PEP.


Assuntos
Fragmentos Fab das Imunoglobulinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Vacinas Antirrábicas/administração & dosagem , Vacinas Antirrábicas/efeitos adversos , Raiva/prevenção & controle , Anafilaxia/etiologia , Animais , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Farmacovigilância , Profilaxia Pós-Exposição , Vigilância de Produtos Comercializados , Vacinas Antirrábicas/imunologia , Estudos Retrospectivos
12.
Adv Exp Med Biol ; 1053: 119-153, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29549638

RESUMO

The failing efficacy of antibiotics and the high mortality rate among high-risk patients calls for new treatment modalities for bacterial infections. Due to the vastly divergent pathogenesis of human pathogens, each microbe requires a tailored approach. The main modes of action of anti-bacterial antibodies are virulence factor neutralization, complement-mediated bacterial lysis and enhancement of opsonophagocytic uptake and killing (OPK). Gram-positive bacteria cannot be lysed by complement and their pathogenesis often involves secreted toxins, therefore typically toxin-neutralization and OPK activity are required to prevent and ameliorate disease. In fact, the success stories in terms of approved products, in the anti-bacterial mAb field are based on toxin neutralization (Bacillus anthracis, Clostridium difficile). In contrast, Gram-negative bacteria are vulnerable to antibody-dependent complement-mediated lysis, while their pathogenesis rarely relies on secreted exotoxins, and involves the pro-inflammatory endotoxin (lipopolysaccharide). Given the complexity of bacterial pathogenesis, antibody therapeutics are expected to be most efficient upon targeting more than one virulence factor and/or combining different modes of action. The improved understanding of bacterial pathogenesis combined with the versatility and maturity of antibody discovery technologies available today are pivotal for the design of novel anti-bacterial therapeutics. The intensified research generating promising proof-of-concept data, and the increasing number of clinical programs with anti-bacterial mAbs, indicate that the field is ready to fulfill its promise in the coming years.


Assuntos
Antibacterianos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Imunoconjugados/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Bactérias/imunologia , Bactérias/patogenicidade , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Citotoxicidade Imunológica , Interações Hospedeiro-Patógeno , Humanos , Imunoconjugados/efeitos adversos , Imunoconjugados/imunologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/imunologia , Virulência
13.
Cardiovasc Ther ; 34(5): 330-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27327862

RESUMO

AIMS: To compare three glycoprotein IIb/IIIa receptor antagonists (GPIs) in terms of platelet inhibition and major adverse cardiac events (MACEs), and assess the rate of bleeding and MACEs between GPIs and coadministered P2Y12 agents. METHODS: Eighty-three acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) with planned GPI use were randomized to receive high-dose bolus tirofiban, double-bolus eptifibatide, or abciximab followed by a 12-hour infusion. Glycoprotein IIb/IIIa platelet receptor inhibition was measured at baseline and at 10 minutes, 1 hour, and 24 hours postbolus dose. Major adverse cardiac events and bleeding complications at 30 days were documented. The incidence of MACEs and bleeding in patients receiving ticagrelor or prasugrel were compared to those given clopidogrel. RESULTS: There were no statistically significant differences in platelet inhibition between GPIs at 10 minutes (P=.085) and 1 hour (P=.337). At 24 hours, abciximab achieved statistically significantly higher median [interquartile range] platelet inhibition (75 [65-88]%) compared to tirofiban (28 [3-56]%; P<.0001) and eptifibatide (44 [31-63]%; P=.007). There were no differences in bleeding or MACEs depending on GPI or P2Y12 inhibitor administered. CONCLUSIONS: Glycoprotein receptor inhibitors achieve similar levels of platelet inhibition at 10 minutes and 1 hour; however, abciximab maintains this benefit 24 hours after bolus dose. We did not witness an increased rate of bleeding in patients given new potent P2Y12 inhibitors and a GPI in the modern era.


Assuntos
Síndrome Coronariana Aguda/terapia , Anticorpos Monoclonais/administração & dosagem , Plaquetas/efeitos dos fármacos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Tirosina/análogos & derivados , Abciximab , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Adenosina/administração & dosagem , Adenosina/análogos & derivados , Idoso , Anticorpos Monoclonais/efeitos adversos , Plaquetas/metabolismo , Clopidogrel , Quimioterapia Combinada , Eptifibatida , Feminino , Hemorragia/induzido quimicamente , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , New South Wales , Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Receptores Purinérgicos P2Y12/sangue , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Fatores de Risco , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Fatores de Tempo , Tirofibana , Resultado do Tratamento , Tirosina/administração & dosagem , Tirosina/efeitos adversos
14.
Heart Lung ; 45(5): 464-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27340007

RESUMO

BACKGROUND: Thrombocytopenia is a possible side effect of routinely administered medical agents widely used in the management of patients with acute coronary syndromes (ACS). It is usually observed within 24 h after abciximab infusion. Differential diagnosis is challenging and the management controversial. METHODS: We present a case of abciximab-induced thrombocytopenia which occurred after a standard treatment. RESULTS: A 57-year-old male was admitted with ST-segment elevation ACS. Coronary angiography revealed an acute occlusion of the diagonal branch by massive thrombus. The patient was administered clopidogrel and acetylsalicylic acid followed by unfractionated heparin and abciximab according to the current guidelines. A rapid progression of thrombocytopenia up to 1 × 10(9)/L was observed. A total of 5 pooled platelet units were transfused and intravenous dexamethasone. Dual antiplatelet therapy was continued. CONCLUSION: Although specific mechanisms of abciximab-related thrombocytopenia are still unclear and the management is not well established, the patient responded well to the therapy and his recovery was uneventful.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Trombocitopenia/etiologia , Abciximab , Anticorpos Monoclonais/uso terapêutico , Aspirina/uso terapêutico , Angiografia Coronária , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Índice de Gravidade de Doença , Trombocitopenia/diagnóstico , Fatores de Tempo
17.
Coron Artery Dis ; 27(4): 267-72, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26848534

RESUMO

BACKGROUND: The aim of this study was to evaluate access-site complications in patients with ST-segment elevation myocardial infarction treated with a transradial primary percutaneous coronary intervention relative to three different P2Y12 platelet inhibitors. PATIENTS AND METHODS: We enrolled 334 consecutive patients (76.9% men, age: 59.4±9.1 years) treated by one of the following: clopidogrel (n=118), prasugrel (n=102), and ticagrelor (n=114). The use of the IIb/IIIa inhibitor, abciximab, was left to the operators' discretion. The time needed to achieve patent hemostasis, compression time, and local complications were analyzed. RESULTS: The baseline characteristics were similar in all three P2Y12 platelet inhibitor groups. Abciximab was used in 72 (21.6%) patients. Administration of abciximab was associated with a higher incidence of grade II and III hematomas (23.6 vs. 5.0%, P<0.0001, and 5.6 vs. 1.1%, P=0.041, respectively). Among different platelet P2Y12 receptor inhibitor groups, the incidences of hematomas grade II and III were similar in patients who did (P≥0.14) and did not (P≥0.31) receive abciximab. There were no grade IV or V hematomas in any of the groups. Patent hemostasis was achieved faster (24.5±13.4 vs. 43.5±30.0 min, P<0.0001) and compression time was shorter (113.2±53.6 vs. 217.8±115.5 min, P<0.0001) when abciximab was not used. Radial artery occlusion occurred in one (0.3%) patient. CONCLUSION: After transradial primary percutaneous coronary intervention, early patent hemostasis and short artery compression times were associated with a higher incidence of local hematomas. The incidence of hematomas was dependent on the use of abciximab, but unrelated to the type of P2Y12 inhibitor used. All hematomas were without clinical consequences.


Assuntos
Cateterismo Periférico/efeitos adversos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Artéria Radial , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Abciximab , Adenosina/efeitos adversos , Adenosina/análogos & derivados , Idoso , Anticorpos Monoclonais/efeitos adversos , Cateterismo Periférico/métodos , Clopidogrel , Feminino , Hematoma/induzido quimicamente , Hemorragia/prevenção & controle , Técnicas Hemostáticas , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/efeitos dos fármacos , Cloridrato de Prasugrel/efeitos adversos , Punções , Artéria Radial/diagnóstico por imagem , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Ticagrelor , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Fatores de Tempo , Resultado do Tratamento
18.
Biomed Res Int ; 2016: 8587164, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28097150

RESUMO

Integrin αIIbß3 plays a crucial role in the process of platelet aggregation. Three integrin αIIbß3 antagonists (abciximab, eptifibatide, and tirofiban) have been approved by FDA for clinical use. Unfortunately, they all showed severe side effects such as thrombocytopenia and bleeding risk. Thus, researches on the development of more effective and safer antiplatelet agents are needed. In this manuscript we reported a novel naphthalenic derivative compound ND-1 with potent antithrombotic effect and lower bleeding risk. ND-1 inhibited ADP-, collagen-, thrombin-, and U46619-induced platelet aggregation with IC50 values of 1.29, 14.46, 12.84, and 40.24 µM, respectively. Mechanism studies indicated that ND-1 inhibited the binding of fibrinogen to integrin αIIbß3 in a dose-dependent manner with an IC50 value of 3.12 µM. ND-1 inhibited P-selectin expression induced by ADP, collagen, thrombin, and U46619 on the surface of platelets. Additionally, this compound reduced platelets spreading to the immobilized fibrinogen. In vivo, ND-1 potently decreased thrombus formation in an arteriovenous shunt thrombosis model in rats and slightly prolonged bleeding time in a tail cutting model in mice. Taken together, our results reveal that ND-1 is a novel antagonist of αIIbß3 with strong antithrombotic effect and lower bleeding risk.


Assuntos
Fibrinogênio/metabolismo , Integrina alfa2/metabolismo , Integrina beta3/metabolismo , Naftalenos/administração & dosagem , Trombose/tratamento farmacológico , Abciximab , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Modelos Animais de Doenças , Eptifibatida , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/patologia , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Camundongos , Peptídeos/efeitos adversos , Peptídeos/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Ratos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombocitopenia/patologia , Trombose/patologia , Tirofibana , Tirosina/efeitos adversos , Tirosina/análogos & derivados , Tirosina/uso terapêutico
19.
Cardiovasc Revasc Med ; 17(1): 19-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26626961

RESUMO

BACKGROUND: Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) poses a high-risk for distal coronary thromboembolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and efficacy of these drugs to improve outcomes in this setting are understudied. METHODS: Patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of ≥1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1:1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30days and up to 1year. RESULTS: The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57-2.21, p=0.73). At 1-year follow-up, MACCE rates were also similar (32.5% vs. 33.9%, HR: 0.97, 95% CI: 0.59-1.59). Major bleeding (BARC types 3a-c) was higher in the abciximab group (11.9% vs. 4.2%, OR: 2.80, 95% CI: 1.01-7.77). Ischemic outcomes did not differ among patients with acute coronary syndromes. CONCLUSION: The use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding.


Assuntos
Anticorpos Monoclonais/farmacologia , Trombose Coronária/prevenção & controle , Fragmentos Fab das Imunoglobulinas/farmacologia , Intervenção Coronária Percutânea , Veia Safena/cirurgia , Abciximab , Idoso , Anticorpos Monoclonais/efeitos adversos , Feminino , Hemorragia/etiologia , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacologia , Resultado do Tratamento
20.
Am Heart J ; 170(6): 1116-23, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26678633

RESUMO

BACKGROUND: Thrombus burden and distal embolization are predictive of no-reflow during primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). We sought to compare the efficacy of pharmacological and catheter-based strategies for thrombus in patients with STEMI and high atherothrombotic burden. METHODS: Between January 2012 and December 2013, 128 STEMI patients undergoing primary PCI at 5 centers were randomly assigned in a 2 × 2 factorial design to intracoronary (IC) abciximab bolus (via the guide catheter) versus intralesion (IL) abciximab bolus, each with versus without aspiration thrombectomy (AT). Study end points were residual intrastent atherothrombotic burden, defined as the number of cross-sections with residual tissue area >10% as assessed by optical coherence tomography, and indices of angiographic and myocardial reperfusion. RESULTS: Residual intrastent atherothrombotic burden did not significantly differ with IL versus IC abciximab (median [interquartile range] 6.0 [1-15] vs 6.0 [2-11], P = .806) and with AT versus no aspiration (6.0 [1-13] vs 6.0 [2-12], P = .775). Intralesion abciximab administration was associated with improved angiographic myocardial reperfusion in terms of thrombolysis in myocardial infarction (TIMI) flow (3 [3-3] vs 3 [2-3], P = .040), corrected TIMI frame count (12 ± 5 vs 17 ± 16, P = .021), and myocardial blush grade (3 [2-3] vs 3 [2-3], P = .035). In particular, IL abciximab was associated with higher occurrence of final TIMI 3 flow (90% vs 73.8%, P = .032) and myocardial blush grade 3 (71.6% vs 52.4%, P = .039). Conversely, AT had no significant effect on indices of angiographic or myocardial reperfusion. CONCLUSIONS: In patients with STEMI and high thrombotic burden, neither IL versus IC abciximab nor AT versus no aspiration reduced postprocedure intrastent atherothrombotic burden in patients with STEMI undergoing primary PCI. However, IL abciximab improved indices of angiographic and myocardial reperfusion compared to IC abciximab, benefits not apparent with AT.


Assuntos
Anticorpos Monoclonais , Reestenose Coronária , Fragmentos Fab das Imunoglobulinas , Infarto do Miocárdio , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Trombectomia , Trombose , Abciximab , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Angiografia Coronária/métodos , Reestenose Coronária/diagnóstico , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Reperfusão Miocárdica/métodos , Fenômeno de não Refluxo/diagnóstico , Fenômeno de não Refluxo/etiologia , Fenômeno de não Refluxo/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento
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