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1.
Blood Adv ; 5(5): 1504-1512, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33683339

RESUMO

Terminal complement inhibition is the standard of care for atypical hemolytic uremic syndrome (aHUS). The optimal duration of complement inhibition is unknown, although indefinite therapy is common. Here, we present the outcomes of a physician-directed eculizumab discontinuation and monitoring protocol in a prospective cohort of 31 patients that started eculizumab for acute aHUS (and without a history of renal transplant). Twenty-five (80.6%) discontinued eculizumab therapy after a median duration on therapy of 2.37 (interquartile range: 1.06, 9.70) months. Eighteen patients discontinued per protocol and 7 because of nonadherence. Of these, 5 (20%) relapsed; however, relapse rate was higher in the case of nonadherence (42.8%) vs clinician-directed discontinuation and monitoring (11.1%). Four of 5 patients who relapsed were successfully retreated without a decline in renal function. One patient died because of recurrent aHUS and hypertensive emergency in the setting of nonadherence. Nonadherence to therapy (odds ratio, 8.25; 95% confidence interval, 1.02-66.19; P = .047) was associated with relapse, whereas the presence of complement gene variants (odds ratio, 1.39; 95% confidence interval, 0.39-4.87; P = .598) was not significantly associated with relapse. Relapse occurred in 40% (2 of 5) with a CFH or MCP variant, 33.3% (2 of 6) with other complement variants, and 0% (0 of 6) with no variants (P = .217). There was no decline in mean glomerular filtration rate from the date of stopping eculizumab until end of follow-up. In summary, eculizumab discontinuation with close monitoring is safe in most patients, with low rates of aHUS relapse and effective salvage with eculizumab retreatment in the event of recurrence.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Proteínas do Sistema Complemento , Taxa de Filtração Glomerular , Humanos , Estudos Prospectivos , Recidiva
2.
Cochrane Database Syst Rev ; 3: CD012862, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33783815

RESUMO

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies. OBJECTIVES: To evaluate the benefits and harms of interventions for aHUS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs. SELECTION CRITERIA: All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed. MAIN RESULTS: We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab. AUTHORS' CONCLUSIONS: When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/mortalidade , Viés , Inativadores do Complemento/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Qualidade de Vida , Microangiopatias Trombóticas/tratamento farmacológico
3.
BMJ Case Rep ; 14(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637496

RESUMO

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) that presents with renal insufficiency, thrombocytopaenia and microangiopathic haemolytic anaemia. Typical HUS is associated with Shiga toxin while atypical HUS (aHUS) is due to overactivation of the alternative complement pathway. aHUS has numerous causes, including drugs, with rare reports of carfilzomib, a proteasome inhibitor used in multiple myeloma, as causative agent. Cases vary in presentation, presenting a diagnostic challenge. Historically, TMAs were treated with plasma exchange. aHUS, however, is considered refractory to plasma exchange and best treated with eculizumab, a monoclonal antibody targeting C5, a terminal complement protein. We report a patient with history of multiple myeloma who presented with headaches, elevated blood pressure, petechiae, ecchymosis and haemolytic anaemia. His condition was determined to be carfilzomib-induced aHUS and he was successfully treated with eculizumab. Early detection and treatment of drug-induced aHUS is vital in reducing morbidity and mortality related to the condition.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Humanos , Masculino , Oligopeptídeos/efeitos adversos
4.
Ter Arkh ; 92(6): 76-80, 2020 Jul 09.
Artigo em Russo | MEDLINE | ID: mdl-33346497

RESUMO

Atypical hemolytic-uremic syndrome (aHUS) is a chronic systemic disease of a genetic nature, which is based on uncontrolled activation of the alternative complement pathway, leading to generalized thrombosis in the vessels of the microvasculature (complement-mediated thrombotic microangiopathy). To date, therapy with eculizumab is the most effective and pathogenetically substantiated method of treating patients with ASH. Using the example of three clinical cases of patients with a verified diagnosis of aHUS, the high efficiency and safety of the worlds first bioanalogue of eculizumab in the treatment of adult patients with aHUS (complement-mediated thrombotic microangiopathy) was demonstrated.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Medicamentos Biossimilares , Preparações Farmacêuticas , Adulto , Anticorpos Monoclonais Humanizados , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Humanos , Federação Russa
5.
Transplant Proc ; 52(1): 146-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31924403

RESUMO

Atypical hemolytic uremic syndrome (aHUS) after kidney transplantation is rare and carries a grave outcome. We present a single-center experience of all aHUS cases since the program's inception. Six patients were diagnosed with aHUS, all after kidney transplants, except for 1 patient. All had nonreactive crossmatches. Delayed graft function (DGF) occurred in 2 patients. Five patients developed aHUS after transplant; 4 (80%) of these patients manifested aHUS ≤ 14 days. All were confirmed by allograft biopsy. Genetic testing was abnormal in all patients except for 1 patient. Actual patient and graft survival during the first year was 100% and 83.3%, respectively. A single graft was lost early in the study secondary to aHUS (eculizumab was not used in the treatment process). Prophylactic and therapeutic use of eculizumab salvaged all other cases. At 1 year, mean creatinine level was 1.9 mg/dL (range, 1.3-2.5). After 6 months of eculizumab treatment (halted in 2 cases) 1 patient had recurrence 2 months later and eculizumab was restarted. However, graft function continued to worsen, and the graft was ultimately lost at 20 months after kidney transplantation. High index of suspicion, prompt diagnosis, and utilization of eculizumab are key to successful salvage of allografts in cases of aHUS after kidney transplantation. aHUS can be prevented by prophylactic use of eculizumab. It still needs to be determined when and if eculizumab therapy can be safely discontinued.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/etiologia , Biópsia , Creatinina/sangue , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Recidiva
7.
Eur J Ophthalmol ; 30(3): NP14-NP17, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30841747

RESUMO

PURPOSE: To report a case of Purtscher-like retinopathy due to atypical hemolytic uremic syndrome and the changes seen in the optical coherence tomography angiography before and after treatment with eculizumab. CASE DESCRIPTION: A 22-year-old man with an unremarkable medical history presented with acute, bilateral blurred vision and headache of 1-week duration. Best corrected visual acuity of 20/50 and 20/40, respectively, in the patient's right eye and left eye. Funduscopy revealed multiple cotton-wool spots associated with intrarretinal fluid. Swept source optical coherence tomography revealed multifocal retinal detachments with increased choroidal thickness. Optical coherence tomography angiography showed areas of ischemia in both capillary plexus. Due to concurrent symptoms and laboratory analysis, he was diagnosed with atypical hemolytic uremic syndrome and secondary Purtscher-like retinopathy; therefore, treatment with eculizumab was initiated. After 2 months revascularization of the previous ischemic areas was seen in the optical coherence tomography angiography that were correlated with best corrected visual acuity improvement. CONCLUSION: Our findings suggest that evaluation of the macular capillary plexus revascularization by optical coherence tomography angiography during the disease could help to predict an improvement of best corrected visual acuity in these patients and the measurement of choroidal thickness could give us information about the resolution of the pathologic process.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Angiografia por Tomografia Computadorizada , Angiofluoresceinografia/métodos , Seguimentos , Humanos , Masculino , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto Jovem
8.
Nephrol Dial Transplant ; 35(2): 298-303, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29992261

RESUMO

BACKGROUND: The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined. METHODS: Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients. RESULTS: Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation. CONCLUSIONS: Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/uso terapêutico , Neisseria meningitidis/imunologia , Animais , Complemento C5/antagonistas & inibidores , Inativadores do Complemento/efeitos adversos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/prevenção & controle , Neisseria meningitidis/efeitos dos fármacos , Coelhos , Falha de Tratamento , Vacinação , Vacinas Conjugadas/uso terapêutico
9.
Obstet Gynecol ; 134(6): 1215-1218, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31764731

RESUMO

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION: Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Diabetes Mellitus , Pré-Eclâmpsia/diagnóstico , Complicações na Gravidez , Diagnóstico Pré-Natal , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Segundo Trimestre da Gravidez , Gravidez Prolongada
10.
Transfus Med Rev ; 33(4): 256-265, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31703946

RESUMO

Dysregulation of the complement system underlies the pathophysiology of many diseases. Renewed interest in complement occurred with the recognition that its therapeutic inhibition was possible. Terminal complement blockade with the anti-C5 monoclonal antibody eculizumab significantly changed management and clinical outcomes of patients with paroxysmal nocturnal hemoglobinuria, and served as a proof of concept for other complement-mediated diseases. Eculizumab is also approved for atypical hemolytic uremic syndrome and myasthenia gravis. Multiple new disease indications have been identified, and novel complement inhibitors are in various stages of development, with several currently in human trials. Beyond C5, these new drugs block proximal complement, pathway-specific targets, convertase activity, and anaphylatoxin function. Though monoclonal antibodies are still common, peptides, RNAi, and small molecule inhibitors provide the opportunity for different administration routes and schedules. Several challenges still exist or will soon present themselves, including mitigation of infection risk, effective monitoring strategies, and how to choose between therapeutics when more than one is available. In this review, we will describe the lessons learned from the "eculizumab era," present many of the novel therapeutics currently or soon to be in trials, and highlight some of the challenges that will require attention as the field progresses.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/fisiologia , Hemoglobinúria Paroxística/tratamento farmacológico , Humanos , Miastenia Gravis/tratamento farmacológico , Microangiopatias Trombóticas/tratamento farmacológico
11.
Clin J Am Soc Nephrol ; 14(12): 1719-1732, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694864

RESUMO

BACKGROUND AND OBJECTIVES: Atypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Complement activation was assessed by exposing endothelial cells to sera or activated-patient plasma-citrated plasma mixed with a control sera pool (1:1)-to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included. RESULTS: Acute phase atypical hemolytic uremic syndrome-activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6-9 months. Complement activation in those with malignant hypertension was at control levels. CONCLUSIONS: The proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.


Assuntos
Ativação do Complemento , Microangiopatias Trombóticas/imunologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Feminino , Síndrome HELLP/imunologia , Humanos , Masculino , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/imunologia , Gravidez , Microangiopatias Trombóticas/tratamento farmacológico
12.
Brasília; CONITEC; nov. 2019.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1120405

RESUMO

INTRODUÇÃO: A Síndrome Hemolítica Urêmica (SHU) é uma desordem do sistema microvascular, cuja causa mais frequente são as infecções por bactérias produtoras de Shiga-toxina. Em cerca de 10% dos casos de SHU, a causa não está associada com a Shiga-toxina e, então, a doença passa a ser classificada como Síndrome Hemolítica Urêmica atípica (SHUa). Por sua vez, a SHUa é causada por anormalidades que prejudicam os mecanismos de controle e provocam a hiperativação da via alternativa do complemento. A doença é caracterizada pela tríade: anemia hemolítica microangiopática (AHMA), trombocitopenia e falência renal aguda. A prevalência mundial da SHUa varia de 2,7 a 5,5 casos a cada um milhão de habitantes, com uma incidência aproximada de 0,4 casos por um milhão de pessoas. Cerca de 60% dos casos são diagnosticados na infância e 40% na idade adulta. Atualmente, não há PCDT do Ministério da Saúde para o tratamento da SHUa. PERGUNTA: O medicamento eculizumabe é eficaz, efetivo e seguro para o tratamento da SHUa? INDICAÇÃO: Tratamento de pacientes com SHUa. EVIDÊNCIAS CIENTÍFICAS: Foram incluídos 12 estudos, sendo duas revisões sistemáticas (RS) de ensaios clínicos fase II, três ensaios clínicos fase II e sete estudos de coorte. Os resultados de eficácia demonstram uma frequência de resposta completa à microangiopatia trombótica (MAT) superior a 60% na maioria dos estudos incluídos. A frequência do status livre de MAT foi superior a 80% em todos os estudos que avaliaram esse desfecho. Houve melhora da qualidade de vida nos estudos que analisaram tal desfecho. Entre os EA relatados os mais comuns foram hipertensão, diarreia, infecções do trato respiratório e urinário e distúrbios do sangue e sistema linfático. Foram relatadas as seguintes reações adversas graves: sepse meningocócica, agitação, pneumonia, abscesso prostático e infecção por herpes zoster. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Foram considerados três cenários, um no qual todos os pacientes com SHUa utilizarão o eculizumabe e os outros com market share variando de 30 a 50% e 50 a 70%. Estimou-se que o impacto orçamentário decorrente da incorporação do eculizumabe para SHUa pode variar de 3.185.292.280,56 (599 pacientes) a 728.402.942,29 (364 pacientes) na população adulta e de 2.490.978.820,07 (899 pacientes) a 569.939.901,84 (546 pacientes) na população pediátrica. AVALIAÇÃO ECONÔMICA: Foi elaborada uma avaliação econômica baseada no modelo de Markov para analisar a relação de custo-efetividade do eculizumabe em comparação com a terapia de suporte convencional. A razão de custo-efetividade incremental foi de 7.905.416,28 reais. CONSULTA PÚBLICA: A Consulta Pública nº 40 foi realizada entre os dias 24/07/2019 e 12/08/2019. Foram recebidas 1280 contribuições, sendo 280 pelo formulário para contribuições técnico-científicas e 1000 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação das contribuições encaminhadas pela Consulta Pública n° 40/2019, o plenário da CONITEC entendeu que não foram apresentadas novas evidências que justificassem a alteração da recomendação inicial. RECOMENDAÇÕES FINAL DA CONITEC: Os membros presentes deliberaram, por unanimidade, recomendar a não incorporação, ao SUS, do eculizumabe para tratamento da síndrome hemolítico urêmica atípica. Foi assinado o Registro de Deliberação nº 472/2019. DECISÃO: Não incorporar o eculizumabe para o tratamento da síndrome hemolítica urêmica atípica, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 56 publicada no Diário Oficial da União nº 224, seção 1, página 79, em 20 de novembro de 2019.


Assuntos
Humanos , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
13.
Front Immunol ; 10: 2166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611870

RESUMO

Defective complement action is a cause of several human glomerular diseases including atypical hemolytic uremic syndrome (aHUS), anti-neutrophil cytoplasmic antibody mediated vasculitis (ANCA), C3 glomerulopathy, IgA nephropathy, immune complex membranoproliferative glomerulonephritis, ischemic reperfusion injury, lupus nephritis, membranous nephropathy, and chronic transplant mediated glomerulopathy. Here we summarize ongoing clinical trials of complement inhibitors in nine glomerular diseases and show which inhibitors are used in trials for these renal disorders (http://clinicaltrials.gov).


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome Hemolítico-Urêmica Atípica , Inativadores do Complemento/uso terapêutico , Glomerulonefrite , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Síndrome Hemolítico-Urêmica Atípica/patologia , Ensaios Clínicos como Assunto , Ativação do Complemento/efeitos dos fármacos , Ativação do Complemento/imunologia , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Humanos
14.
J Am Soc Nephrol ; 30(12): 2449-2463, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31575699

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country. METHODS: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016. RESULTS: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients. CONCLUSIONS: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Transplante de Rim , Adulto , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/cirurgia , Proteínas Inativadoras do Complemento C3b/genética , Proteínas do Sistema Complemento/análise , Feminino , França , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes Quiméricas/genética , Cuidados Pré-Operatórios , Modelos de Riscos Proporcionais , Recidiva , Sistema de Registros , Estudos Retrospectivos , Prevenção Secundária
15.
Acta Med Port ; 32(10): 673-675, 2019 Oct 01.
Artigo em Português | MEDLINE | ID: mdl-31625881

RESUMO

The atypical hemolytic uremic syndrome comprises a thrombotic microangiopathy resulting from the complement alternate pathway hyperactivation. Its severity requires early diagnosis and treatment. The differential diagnosis includes typical hemolytic uremic syndrome (associated with Shiga toxin) and thrombotic thrombocytopenic purpura (associated with deficient activity of ADAMTS13). The only specific treatment currently available for atypical hemolytic uremic syndrome is eculizumab. We describe the case of a child with atypical hemolytic uremic syndrome diagnosed in the context of bloody diarrhea, complicated by neurological involvement that posed several diagnostic and therapeutic challenges.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Criança , Diagnóstico Diferencial , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia
16.
BMJ Case Rep ; 12(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31519719

RESUMO

Atypical haemolytic uraemic syndrome (aHUS) is a disease of complement dysregulation and can be fatal if not treated in a timely manner. Although normally associated with triggers such as infection or pregnancy, this case demonstrates acute pancreatitis as the triggering event. The patient's initial presentation of thrombocytopaenia and acute renal failure was first attributed to a systemic inflammatory response syndrome due to pancreatitis, but with detailed history and further laboratory investigation, we were able to show that patient was having symptoms associated with aHUS. On early recognition of aHUS, this patient was able to receive the proper standard of care with eculizumab and had a full recovery while preventing renal failure. When patients present with thrombocytopaenia and renal failure in acute pancreatitis, we want to ensure physicians keep aHUS on the differential.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/etiologia , Pancreatite/complicações , Insuficiência Renal/etiologia , Trombocitopenia/etiologia , Doença Aguda , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Pediatr Nephrol ; 34(12): 2601-2604, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520126

RESUMO

BACKGROUND: Eculizumab has caused a revolution in the treatment and prognosis of atypical hemolytic uremic syndrome. Early initiation of treatment is recommended to increase chances of renal recovery. CASE-DIAGNOSIS/TREATMENT: We describe a boy with atypical hemolytic uremic syndrome who started eculizumab therapy after being on dialysis for 4.5 months, with complete anuria. With treatment, he was weaned off dialysis. CONCLUSION: We review the evidence in the literature and discuss the possible mechanism by which eculizumab induces renal recovery even in patients already on prolonged dialysis. This case report highlights the importance of a treatment trial with eculizumab, even in patients already on prolonged dialysis.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Diálise Renal , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento
18.
Transplant Proc ; 51(7): 2295-2297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400975

RESUMO

PURPOSE: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic anemia, thrombocytopenia, and acute kidney injury. HUS is mostly associated with diarrhea (90%). However, 10% of cases are not associated with diarrhea and are thus called as atypical HUS (aHUS); these cases are usually caused by dysregulation of the complement system. Eculizumab, a monoclonal antibody against C5, is the drug of choice for treating aHUS. Herein we aimed to present 8 cases of renal transplantation performed on patients with aHUS. MATERIALS AND METHODS: A total of 8 patients who had been diagnosed with aHUS between the years 2012 to 2018 were enrolled and underwent transplantations. All patients received induction treatment, standard immunosuppresive treatment (tacrolimus, mycophenolic acid, prednisolone), and eculizumab. Eculizumab was administered at a dosage of 900 mg/wk for the first month and 1200 mg every 2 weeks thereafter. Patients were followed up and recorded in terms of demographic features, serum creatinine, lactate dehydrogenase, acute rejection episodes, and allograft outcomes. RESULTS: Mean age was 34 ± 8 years (Male/Female: 6/2). One of the patients had a second transplantation. Median hemodialysis vintage (25%-75% interquartile range) was 37 (9-63) months. Four patients had pretransplant plasmapheresis and 2 patients had posttransplant plasmapheresis. Induction treatment was ATG in 7 patients, and basiliximab was used only in 1 patient. The median follow-up period was 25 (13-59) months. Mean serum creatinine levels were 1.9 ± .6, 1.2 ± .7, and 1 ± .1 mg/dL for the first day, first month, and last values, respectively. Mean lactate dehydrogenase levels were 286 ± 203, 239 ± 27, and 218 ± 86 U/L for first day, first month, and last values, respectively. None of the patients had an acute rejection episode. Currently, all patients have functioning allografts. CONCLUSION: Patients with aHUS may be transplanted successfully with eculizumab with good allograft outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/cirurgia , Inativadores do Complemento/uso terapêutico , Transplante de Rim , Adulto , Terapia Combinada , Creatinina/análise , Feminino , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Plasmaferese , Período Pós-Operatório , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
19.
BMC Nephrol ; 20(1): 307, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390992

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a disorder of the microvasculature with hemolytic anemia, thrombocytopenia and acute kidney injury. Nowadays, aHUS is successfully treated with eculizumab, a humanized, chimeric IgG2/4 kappa antibody, which binds human complement C5 and blocks generation of C5a and membrane-attack-complex. CASE PRESENTATION: A 25-year-old woman with end stage renal disease due to relapsing atypical hemolytic uremic syndrome had a relapse of the disease during pregnancy. She was treated with eculizumab. We measured reduced formation of the membrane-attack complex in newborn's umbilical cord vein blood using the sensitive and specific Palarasah-Nielsen-ELISA. CONCLUSIONS: Eculizumab treatment of the mother with end stage renal disease may cause reduced innate immunity which could render newborns more susceptible to infections.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Complexo de Ataque à Membrana do Sistema Complemento/efeitos dos fármacos , Complicações na Gravidez/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/metabolismo , Síndrome Hemolítico-Urêmica Atípica/imunologia , Complemento C3/metabolismo , Complemento C5a/metabolismo , Complemento C9/metabolismo , Inativadores do Complemento/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Sangue Fetal/imunologia , Humanos , Recém-Nascido , Falência Renal Crônica/tratamento farmacológico , Gravidez , Recidiva
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