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1.
Rev. Méd. Inst. Mex. Seguro Soc ; 60(2): 201-210, abr. 2022. ilus, tab
Article in Spanish | LILACS | ID: biblio-1367344

ABSTRACT

El manejo del asma grave descontrolada con biológicos es un área de extrema dificultad, dada la escasez de información respecto a los criterios de inicio de los mismos, las variables a evaluar para determinar la eficacia y seguridad de su manejo, los puntos de corte para determinar el momento oportuno para cambiar o agregar otro biológico y el proceso para disminuir o retirar los esteroides. Esta revisión incorpora la información más reciente y realiza una propuesta con base en ella.


The management of severe uncontrolled asthma with biologics is an area of extreme difficulty given the scarcity of information regarding their starting criteria, the variables to be evaluated to determine the efficacy and safety of their management, the cut-off points to determine the timing to change or add another biological and the process to decrease or withdraw steroids. This review incorporates the latest information and makes a proposal based on it


Subject(s)
Humans , Male , Female , Asthma/drug therapy , Biological Therapy , Asthma/immunology , Biomarkers/blood , Follow-Up Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use
2.
Medwave ; 22(2): e002118, mar.2022. tab
Article in English, Spanish | LILACS | ID: biblio-1366391

ABSTRACT

Contexto La hemofilia es un trastorno hemorrágico de la coagulación que ocurre en uno de cada 5000 nacimientos masculinos. Los pacientes con hemofilia A grave no tratados tienen complicaciones hemorrágicas, incluyendo sangrados articulares y menor sobrevida. El emicizumab es un anticuerpo monoclonal aprobado por los Estados Unidos para la profilaxis rutinaria de pacientes pediátricos y adultos con hemofilia A grave con inhibidores del factor VIII de coagulación. Objetivos Realizar un estudio de costo-efectividad de la profilaxis con emicizumab para niños y adultos con hemofilia A grave, en comparación con el actual manejo de esos pacientes en el Ministerio de Salud y el Seguro Social de Salud de Perú. Metodología Se modeló la transición del paciente entre estados médicos con la metodología de Markov y se estimó a lo largo de su vida costos y efectos incrementales de emicizumab comparados con el actual manejo. Se estimó el impacto presupuestario de emicizumab proyectando costos netos anuales y su valor presente a cinco años. Resultados Emicizumab generaría ahorros en el Ministerio de Salud entre 14,6 y 16,0 por niño y 11,8 por adulto, en US$ millones actuales, y en el Seguro Social de Salud de 12,8 a 14,9 por niño y 40,1 por adulto. Además, se generan ganancias en efectividad, medidas en años de vida ajustados por calidad, de 0,36 por niño y 0,56 por adulto y de 0,25 por niño y 0,36 por adulto en esas respectivas instituciones. El impacto presupuestario sería un ahorro anual neto, en US$ millones, de 12,8 y 15,0 en esas entidades. Conclusión El actual manejo de la enfermedad es muy costoso y con resultados de salud inferiores a los posibles con emicizumab. Este fármaco produciría grandes ahorros y mejor salud. Ambas entidades debieran implementar protocolos para la profilaxis y tratamiento de la hemofilia y financiarla con presupuesto propio.


Settings Hemophilia is a coagulation disorder that occurs in one in 5000 male births. Patients with untreated severe hemophilia A have hemorrhagic complications, including joint bleeds and decreased survival. Emicizumab is a monoclonal antibody approved by the United States for routine prophylaxis of pediatric and adult patients with severe hemophilia A with factor VIII inhibitors. Objectives To perform a cost-effectiveness study of emicizumab prophylaxis for children and adults with severe hemophilia A compared with the current disease management in the Peruvian Ministry of Health and Social Security Health Insurance. Methods The patient transition between medical states was modeled with Markov methodology, and the lifetime costs and incremental effects of emicizumab compared to current management were estimated. The budgetary impact of emicizumab was estimated by projecting annual net costs and its five-year present value. Results In the Ministry of Health, emicizumab would generate savings between 14.6 and 16.0 per child and 11.8 per adult, in current US$ million. Social Security Health Insurance savings would be 12.8 to 14.9 per child and 40.1 per adult. In addition, this strategy would generate effectiveness gains, measured in quality-adjusted life-years, of 0.36 per child and 0.56 per adult and 0.25 per child, and 0.36 per adult in those respective institutions. The budgetary impact would be a net annual saving of 12.8 and 15.0 US$ million in those entities. Conclusions The current management of hemophilia A is very costly and has health outcomes inferior to those possible with emicizumab. This drug would produce significant savings and better patient health. The Ministry of Health and Social Health Insurance should implement hemophilia prophylaxis and treatment protocols and finance this drug.


Subject(s)
Humans , Male , Child , Adult , Hemophilia A/complications , Hemophilia A/drug therapy , Peru , Factor VIII/therapeutic use , Cost-Benefit Analysis , Antibodies, Bispecific , Antibodies, Monoclonal, Humanized , Hemorrhage/etiology
3.
Arq. Asma, Alerg. Imunol ; 6(1): 4-48, jan.mar.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400091

ABSTRACT

A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.


Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.


Subject(s)
Humans , Therapeutics , Conjunctivitis, Allergic , Diagnosis , Keratoconjunctivitis , Patients , Plants, Medicinal , Pruritus , Psychotherapy , Asthma , Signs and Symptoms , Societies, Medical , Vision, Ocular , Climate Change , Conjunctivitis, Allergic/complications , Conjunctivitis, Allergic/epidemiology , Complementary Therapies , Immunoglobulin E , Serologic Tests , Skin Tests , Allergens , Rhinitis , Rhinitis, Allergic, Seasonal , Probiotics , Acupuncture , Pyroglyphidae , Dermatitis, Atopic , Environmental Pollution , Allergy and Immunology , Antibodies, Monoclonal, Humanized , Omalizumab , Mast Cell Stabilizers , Histamine Antagonists , Hypersensitivity , Immunosuppressive Agents , Immunotherapy , Medicine, Ayurvedic , Mites
5.
Einstein (Säo Paulo) ; 20: eRC6367, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364787

ABSTRACT

ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.


Subject(s)
Humans , Skin Neoplasms/drug therapy , Carcinoma, Squamous Cell/drug therapy , Oral Ulcer , Antibodies, Monoclonal, Humanized , Lymph Nodes
6.
Arq. Asma, Alerg. Imunol ; 5(4): 416-421, out.dez.2021. ilus
Article in English, Portuguese | LILACS | ID: biblio-1399806

ABSTRACT

A dermatite atópica (DA) é uma doença inflamatória crônica da pele, caracterizada por intenso prurido e eczema recorrente. Acomete principalmente a infância, mas tem se tornado bastante prevalente em adolescentes e até em adultos. Apesar de ser geralmente não fatal, apresenta uma carga psicossocial importante para os pacientes e seus familiares. O tratamento da DA envolve a hidratação cutânea e medicações anti-inflamatórias. Em casos graves, pode haver necessidade de terapia sistêmica com imunossupressores como ciclosporina, metotrexato e azatioprina. Mais recentemente, alguns imunobiológicos estão em desenvolvimento para controle da DA. O dupilumabe é um anticorpo monoclonal com ação dupla anti-IL-4/IL-13, liberado para tratamento de crianças a partir de 6 anos com DA grave e adolescentes/adultos com DA moderada a grave. O objetivo deste artigo foi relatar uma série de casos de pacientes adolescentes e adultos com DA grave e sua resposta ao dupilumabe durante a pandemia do COVID-19. Trata-se de quatro pacientes (três do sexo feminino), com piora significativa da DA durante o ano de 2020. Todos tinham história de DA desde a infância, com exames complementares evidenciando sensibilização IgE-mediada para ácaros. Já haviam sido submetidos a diversos tratamentos tópicos e sistêmicos, inclusive a cursos de corticosteroides orais. Nenhum deles havia recebido imunossupressor sistêmico, porém estavam recusando este tipo de tratamento devido ao medo da pandemia. Todos apresentaram boa resposta ao dupilumabe, evidenciada pela redução do número de lesões cutâneas e prurido, com poucos efeitos colaterais. Dois pacientes apresentaram sintomas sugestivos de COVID-19 durante o tratamento com dupilumabe (um com confirmação por PCR), com boa evolução. Concluindo, os pacientes com DA grave possuem grande impacto na qualidade de vida e, durante a pandemia de COVID-19, muitos apresentaram piora significativa do seu quadro dermatológico. Nesse contexto, o dupilumabe se mostrou uma opção terapêutica eficaz e segura para tratamento destes pacientes.


Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczema. It mainly affects childhood but has become quite prevalent in adolescents and even adults. Despite being generally nonfatal, it has an important psychosocial burden for patients and their families. AD treatment involves skin hydration and antiinflammatory medications. In severe cases, systemic therapy with immunosuppressive agents such as cyclosporine, methotrexate, and azathioprine may be necessary. More recently, some biologicals are being developed to control AD. Dupilumab is a monoclonal antibody with anti-IL-4/IL-13 dual-action, approved for the treatment of children from 6 years of age with severe AD and adolescents/adults with moderate to severe AD. This article aimed to report a case series of adolescent and adult patients with severe AD and their response to dupilumab during the COVID-19 pandemic. These are four patients (three female), with a significant worsening of AD during the year 2020. All had a history of AD since childhood, with complementary exams showing IgE-mediated sensitization to mites. They had already undergone several topical and systemic treatments, including courses on oral corticosteroids. None of them had received systemic immunosuppressive agents, but they were refusing this type of treatment due to fear of the pandemic. All had a good response to dupilumab, evidenced by a reduction in the number of skin lesions and pruritus, with few side effects. Two patients had symptoms suggestive of COVID-19 during treatment with dupilumab (one confirmed by PCR) with a good outcome. In conclusion, patients with severe AD have a great impact on quality of life and, during the COVID-19 pandemic, many had a significant worsening of their dermatological condition. In this context, dupilumab proved to be an effective and safe therapeutic option for the treatment of these patients.


Subject(s)
Humans , Adolescent , Young Adult , Dermatitis, Atopic , Antibodies, Monoclonal, Humanized , COVID-19 , Patients , Pruritus , Quality of Life , Asthma , Signs and Symptoms , Azathioprine , Therapeutics , Biological Products , Immunoglobulin E , Interleukin-4 , Interleukin-13 , Rhinitis, Allergic , Mites
9.
Arq. Asma, Alerg. Imunol ; 5(4): 385-394, out.dez.2021. ilus
Article in English | LILACS | ID: biblio-1399793

ABSTRACT

Eosinophilic esophagitis (EoE) is a chronic inflammation in the esophageal mucosa driven by an antigen-mediated abnormal immune response with apparent increasing prevalence worldwide. Genetically predisposed individuals present with a dysfunctional esophageal barrier and an abnormal immune response mediated by Th2 and IgE against certain allergens. Consequently, esophageal lesions can cause dysmotility, fibrosis and loss of esophageal barrier function. Clinical manifestations are age-related and include symptoms of esophageal dysfunction. Diagnosis is established by specific histological features associated with the presence of at least 15 eosinophils per high-power field. Management of EoE includes control of allergic diseases with diet restrictions and/or pharmacological treatment with proton-pump inhibitors and corticosteroids, not completely effective and limited by possible side effects and impairment of quality of life. Although immunological mechanisms of EoE are still less clear than other allergic diseases, biologic trials indicate some promising perspectives for EoE management. The purpose of this review is to present the current evidence of biologic drugs as options for EoE treatment.


Esofagite eosinofílica (EOE) é uma inflamação crônica da mucosa esofágica com resposta imune antígeno-mediada anormal e com aparente aumento mundial na prevalência. Indivíduos geneticamente predispostos se apresentam com quadro de disfunção da barreira esofágica e uma resposta imune, mediada por TH2 e IGE, anormal contra certos alérgenos. Consequentemente, lesões esofágicas podem causar dismotilidade, fibrose e perda da função de barreira. O quadro clínico apresenta variação conforme idade e inclui sintomas de disfunção esofágica. O diagnóstico é estabelecido por achados histológicos específicos associados à presença de, ao menos, 15 eosinófilos por campo de alta potência. O manejo inclui controle do quadro alérgico com restrição dietética e/ou tratamento medicamentoso com bloqueadores da bomba de prótons e corticosteroides. São tratamentos sem completa efetividade, com efeitos colaterais e prejuízo na qualidade de vida. Ainda que os mecanismos imunológicos da EOE sejam menos claros que as demais doenças alérgicas, novos ensaios com imunobiológicos salientam uma perspectiva promissora de tratamento para a EOE. O objetivo desta revisão é apresentar as atuais evidências de uso de imunobiológicos como uma nova opção de terapêutica para a esofagite eosinofílica.


Subject(s)
Humans , Adrenal Cortex Hormones , Diet , Proton Pump Inhibitors , Eosinophilic Esophagitis , Antibodies, Monoclonal, Humanized , Omalizumab , Therapeutics , Biological Products , Fibrosis , Immunoglobulin E , Prevalence , Drug Therapy , Endoscopy , Esophageal Mucosa , Immunity , Inflammation , Antigens
10.
Rev. Hosp. Ital. B. Aires (2004) ; 41(4): 171-175, dic. 2021. tab
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: biblio-1366760

ABSTRACT

Introducción: la amiloidosis AA puede ser una complicación de ciertos trastornos inflamatorios crónicos, aunque entre el 21% y 50% puede ser idiopática. No existe un tratamiento específico. El tocilizumab, dirigido contra el receptor de IL-6 y orientado a disminuir la producción de SAA, podría ser eficaz. Métodos: en este estudio informamos datos de 6 pacientes con amiloidosis AA tratados con tocilizumab monoterapia subcutáneo en el período 2011-2018. Los criterios de valoración principales fueron la mejora clínica y bioquímica de los órganos afectados y los parámetros bioquímicos marcadores de inflamación. Resultados: el riñón estaba afectado en todos los pacientes, manifestándose con caída del filtrado glomerular y síndrome nefrótico. La hemorragia digestiva se presentó en un paciente y otro tenía afectación pulmonar en la biopsia. Luego del posterior al tratamiento, todos mejoraron el hematocrito, la albúmina sérica y el índice de masa corporal. El SAA disminuyó en 5 pacientes. Un paciente mejoró su función renal, mientras 4 se mantuvieron estables. Tres pacientes disminuyeron los valores de proteinuria. Conclusión: el tratamiento con tocilizumab podría ser eficaz en el tratamiento de los pacientes con amiloidosis AA. (AU)


Introduction: AA amyloidosis can be a complication of certain chronic inflammatory disorders, although between 21% and 50% can be idiopathic. There is no specific treatment. Tocilizumab, directed against the IL-6 receptor and aimed at decreasing SAA production, could be effective. Methods: in this study, we report data from 6 patients with AA amyloidosis treated with subcutaneous tocilizumab monotherapy between the period 2011-2018. The main endpoints were the clinical and biochemical improvement of the affected organs and the biochemical parameters markers of inflammation. Results: the kidney was affected in all patients, manifesting with a fall in glomerular filtration rate and nephrotic syndrome. Gastrointestinal bleeding occurred in one patient and another had lung involvement on biopsy. After treatment, all improved hematocrit, serum albumin, and body mass index. SAA decreased in 5 patients. One patient improved his kidney function, while 4 remained stable. Three patients decreased proteinuria values. Conclusion: treatment with tocilizumab could be effective in the treatment of patients with AA amyloidosis. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Serum Amyloid A Protein/drug effects , Antibodies, Monoclonal, Humanized/therapeutic use , Amyloidosis/drug therapy , Body Mass Index , Receptors, Interleukin-6/drug effects , Antibodies, Monoclonal, Humanized/administration & dosage , Glomerular Filtration Rate/drug effects , Gastrointestinal Hemorrhage/complications , Amyloidosis/blood , Inflammation/complications , Lung Diseases/complications , Nephrotic Syndrome/complications
11.
Arq. bras. cardiol ; 117(5): 988-996, nov. 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1350009

ABSTRACT

Resumo Fundamento: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. Objetivo: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. Métodos: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. Resultados: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. Conclusões: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.


Abstract Background: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.


Subject(s)
Humans , Cardiomyopathy, Hypertrophic/prevention & control , Antibodies, Monoclonal, Humanized/therapeutic use , Hypertension/drug therapy , Anticholesteremic Agents/therapeutic use , State Medicine , Brazil , Cost-Benefit Analysis , Hypertrophy, Left Ventricular/prevention & control , Contrast Media , Antibodies, Monoclonal, Humanized/economics , Gadolinium , Anticholesteremic Agents/economics
14.
Arq. Asma, Alerg. Imunol ; 5(3): 232-236, jul.set.2021. ilus
Article in Portuguese | LILACS | ID: biblio-1399211

ABSTRACT

A rinossinusite crônica (RSC) é uma síndrome caracterizada pela inflamação da mucosa nasal e dos seios paranasais por pelo menos 12 semanas, acometendo de 5% a 12% da população geral. A síndrome é associada a alta morbidade e considerada um grande problema de saúde pública devido a sua prevalência, seu custo para a sociedade e ao impacto que acarreta na qualidade de vida dos pacientes e em seu desempenho escolar ou profissional. Ademais, a RSC está associada a diversas comorbidades, como dermatite atópica, distúrbios respiratórios do sono, conjuntivite, otite média, asma e problemas emocionais. O dupilumabe é eficaz e seguro no tratamento da RSC com polipose nasal. A eficácia é progressiva no primeiro ano de tratamento, e a posologia de 300 mg a cada duas semanas é superior em relação à de cada quatro semanas. A interrupção do tratamento com 24 semanas acarreta a perda parcial de seus efeitos benéficos. O imunobiológico também é eficaz no controle da asma nos pacientes que apresentam essa doença como comorbidade. Alguns pacientes podem apesentar aumento transitório de eosinófilos sanguíneos, e 2,7% desenvolveram conjuntivite como reação adversa nos estudos SINUS-24 e SINUS-52. O dupilumabe é uma excelente opção terapêutica no tratamento concomitante de múltiplas doenças caracterizadas pela inflamação de tipo II.


Chronic rhinosinusitis (CRS) is a syndrome characterized by inflammation of the nasal mucosa and paranasal sinuses for at least 12 weeks, affecting 5% to 12% of the general population. The syndrome is associated with high morbidity and is considered a major public health problem because of its prevalence, its cost to society, and the impact it has on patients' quality of life and on their school or professional performance. Furthermore, CRS is associated with several comorbidities, such as atopic dermatitis, sleep-disordered breathing, conjunctivitis, otitis media, asthma, and emotional problems. Dupilumab is effective and safe in the treatment of CRS with nasal polyposis. Effectiveness is progressive in the first year of treatment, and a dosage of 300 mg every two weeks is more effective than that of every four weeks. Discontinuing treatment at 24 weeks results in partial loss of its beneficial effects. The biological drug is also effective in controlling asthma in patients who have this disease as a comorbidity. Some patients may experience a transient increase in blood eosinophils, and 2.7% developed conjunctivitis as an adverse reaction in the SINUS-24 and SINUS-52 studies. Dupilumab is an excellent therapeutic option in the concomitant treatment of multiple diseases characterized by type II inflammation.


Subject(s)
Humans , Rhinitis , Nasal Polyps , Antibodies, Monoclonal, Humanized , Otitis Media , Paranasal Sinuses , Patients , Quality of Life , Asthma , Sinusitis , Therapeutics , Effectiveness , Conjunctivitis , Dermatitis, Atopic , Eosinophils , Nasal Mucosa
15.
Arq. Asma, Alerg. Imunol ; 5(3): 298-301, jul.set.2021. ilus
Article in English | LILACS | ID: biblio-1399398

ABSTRACT

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterized by asthma, peripheral blood eosinophilia, and signs of vasculitis. Glucocorticoids are considered the cornerstone of treatment, but most patients remain steroid-dependent and carry a significant burden of adverse effects. We report a case of a patient with steroid-dependent EGPA successfully treated with mepolizumab. A 36-year-old man presented with persistent rhinitis, dyspnea, wheezing, and dry cough poorly controlled with inhaled therapy. Eosinophilia in peripheral blood and bronchoalveolar lavage fluid was seen. Histological findings from nasal mucosa revealed eosinophilic microabscesses and vasculitis without granulomas compatible with EGPA diagnosis. After daily oral prednisolone (PSL) was started, symptoms and eosinophilia improved, but adverse effects emerged. Attempts at tapering off PSL resulted in worsening of symptoms. He started mepolizumab 300 mg monthly, with clinical improvement and sustained disease remission, which allowed reducing the need for PSL. We present a very disabling steroiddependent EGPA. Mepolizumab was able to taper off PSL while maintaining symptomatic control.


Granulomatose eosinofílica com poliangiite (EGPA) é uma doença multissistêmica caracterizada por asma, eosinofilia no sangue periférico e sinais de vasculite. Os corticoides são considerados a base do tratamento, no entanto, a maioria dos pacientes permanece dependente deste tratamento com os seus efeitos adversos associados. Relatamos o caso de um paciente com granulomatose eosinofílica dependente de esteroides com poliangiite (EGPA) tratado com sucesso com mepolizumabe. Um homem de 36 anos apresentou rinite persistente, dispneia, sibilos e tosse seca mal controlada com terapia inalada. Observou-se eosinofilia no sangue periférico e no lavado broncoalveolar. Os achados histológicos da mucosa nasal revelaram microabscessos eosinofílicos e vasculite sem granulomas compatíveis com o diagnóstico de EGPA. Após o início da prednisolona oral diária (PSL), os sintomas e a eosinofilia melhoraram, mas surgiram efeitos adversos. As tentativas de redução gradual da PSL resultaram no agravamento dos sintomas. Iniciou mepolizumabe 300 mg mensalmente, com melhora clínica e remissão sustentada da doença, o que permitiu reduzir a necessidade de PSL. Apresentamos um EGPA dependente de esteroides muito incapacitante. O mepolizumab foi capaz de diminuir o PSL mantendo o controle sintomático sustentado.


Subject(s)
Humans , Male , Adult , Prednisolone , Granulomatosis with Polyangiitis , Adrenal Cortex Hormones , Antibodies, Monoclonal, Humanized , Signs and Symptoms , Therapeutics , Respiratory Sounds , Rhinitis , Interleukin-5 , Cough , Diagnosis , Dyspnea , Eosinophilia
16.
Arq. Asma, Alerg. Imunol ; 5(2): 195-198, abr.jun.2021. ilus
Article in Portuguese | LILACS | ID: biblio-1398931

ABSTRACT

A urticária é uma lesão cutânea eritematosa, edematosa e pruriginosa, mais prevalente em mulheres entre 30 a 50 anos de idade, sendo classificada em aguda ou crônica. O quadro clínico da urticária crônica espontânea é desencadeado independentemente de estímulos exógenos, podendo ser acompanhado de angioedema em 40% dos casos. O diagnóstico é clínico e a doença pode ser monitorada com escores. O tratamento da urticária crônica espontânea é baseado em anti-histamínicos H1 de segunda geração como primeira linha. A segunda linha se baseia no aumento da dose de anti-histamínicos H1 em até quatro vezes a dose habitual, a terceira linha consiste na associação de imunobiológicos como o omalizumabe, e a quarta linha no uso de ciclosporina. Este relato de caso teve como objetivo analisar a eficácia e segurança do tratamento com dupilumabe na urticária crônica espontânea refratária ao omalizumabe, utilizando os escores de atividade da urticária e o questionário de qualidade de vida em dermatologia. A partir dos resultados obtidos, verificou-se sucesso terapêutico com dupilumabe, que se manteve mesmo após suspensão do medicamento. O uso off label do dupilumabe justificou-se pelo seu mecanismo de ação na fisiopatologia da doença. Este é o primeiro relato de caso brasileiro do uso de dupilumabe para urticária crônica espontânea refratária ao omalizumabe.


Urticaria is an erythematous, edematous, and pruritic skin lesion, most prevalent in women between 30 and 50 years of age, and classified as acute or chronic. The clinical features of spontaneous chronic urticaria are triggered regardless of exogenous stimuli and may be accompanied by angioedema in 40% of cases. The diagnosis is clinical and the disease can be monitored with scores. The first-line treatment of spontaneous chronic urticaria is based on second-generation H1 antihistamines. The second-line treatment is based on increasing the dose of H1 antihistamines by up to four times the standard dose, the third line consists of the association with biologics such as omalizumab, and the fourth line consists of the use of cyclosporine. The present case report aimed to analyze the efficacy and safety of dupilumab treatment for chronic spontaneous urticaria refractory to omalizumab, quantifying clinical improvement and quality of life using urticaria activity scores and a dermatology quality of life questionnaire, respectively. The results obtained showed therapeutic success with dupilumab, which was maintained even after drug suspension. Offlabel use of dupilumab was justified by its mechanism of action in the pathophysiology of the disease. This is the first Brazilian case report of the use of dupilumab for chronic spontaneous urticaria refractory to omalizumab.


Subject(s)
Humans , Female , Young Adult , Antibodies, Monoclonal, Humanized , Omalizumab , Chronic Urticaria , Histamine Antagonists , Histamine H1 Antagonists , Therapeutics , Efficacy , Cyclosporine , Dosage , Angioedema
17.
s.l; CONETEC; 21 mayo 2021.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1224550

ABSTRACT

INTRODUCCIÓN: La evidencia actual muestra que la infección por el SARS-CoV-2 progresa en diferentes etapas. Los síndromes de dificultad respiratoria aguda (SDRA) se observan en una proporción significativa de pacientes frágiles, aproximadamente después de la segunda semana, y no se relacionan sólo con la replicación viral no controlada, sino con la respuesta del huésped.3 Tocilizumab es un anticuerpo monoclonal recombinante humanizado, que actúa a través de la inhibición de la citocina interleucina 6 (IL-6), involucrada en procesos inflamatorios y sistémicos propios del sistema inmune. La Administración de Medicamentos y Alimentos (FDA, su sigla del inglés Food and Drug Administration) de los Estados Unidos, la Agencia Europea de Medicamentos (EMA, su sigla del inglés European Medicines Agency) y Admistración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT ) de nuestro país, han autorizado su uso para el manejo de diversas enfermedades entre las que se incluye la artritis reumatoide, artritis idiopática juvenil sistémica, de células gigantes y artritis idiopática juvenil de múltiples articulaciones. 4-5 Posteriormente (a partir del año 2018) sus indicaciones se ampliaron para su uso en pacientes con afectación grave secundaria al denominado síndrome de liberación de citoquinas (SLC) inducido por células T-CAR. Esta indicación no es el resultado de un desarrollo clínico específico, pero sí un supuesto derivado del uso empírico de tocilizumab en dichas situaciones, donde se postula un incremento de las citocinas pro-inflamatorias, en especial la IL-6.6 En pacientes con COVID-19 grave o crítica que presentan un estado de hiperinflamación la inmunosupresión y el bloqueo de este tipo de receptores de IL-6 se plantea como beneficiosa.7 Se realizó una evaluación de tecnología sanitaria, basada en evidencia proveniente de revisiones sistemáticas vivas y guías de práctica clínica de alta calidad metodológica para brindar parámetros actualizados y balanceados que sean de utilidad para la toma de decisiones en los diferentes niveles de gestión. OBJETIVO: El objetivo del presente informe es evaluar parámetros de eficacia, seguridad, conveniencia y recomendaciones disponibles acerca del uso de tocilizumab para el tratamiento de pacientes con COVID19. MÉTODOS: Efectos en la Salud: Se desarrolló un protocolo sustentado en proyectos que resume activamente la evidencia científica a medida que la misma se hace disponible. Con este fin se utilizó la plataforma Love de Epistemonikos para identificar revisiones sistemáticas "vivas". Se seleccionaron aquellas con una calidad metodológica apropiada evaluada a través de la herramienta AMSTAR-2, y que a su vez llevaran un proceso de actualización frecuente.8 De cada una de las revisiones sistemáticas identificadas se extractaron los efectos de la intervención sobre los desenlaces priorizados como importantes o críticos(mortalidad, ingreso en asistencia ventilatoria mecánica, duración de ventilación mecánica, duración de estadía hospitalaria, mejoría clínica al día 7-28, eventos adversos graves) y la certeza en dichos efectos. Adicionalmente se extractaron datos relacionados con efectos de subgrupo potencialmente relevantes para la toma de decisión, con especial énfasis en el tiempo de evolución y la severidad de la enfermedad. Implementación: Este dominio contempla dossubdominios: la existencia de barreras y facilitadores en nuestro contexto para la implementación de la tecnología evaluada no consideradas en los otros dominios analizados, y los costos comparativos en relación con otras intervenciones similares. Con el objetivo de emitir un juicio de valor sobre la magnitud de dichos costos, se utilizó como comparador al tratamiento con dexametasona, que ha demostrado ser una intervención accesible y de beneficios importantes en el contexto analizado. Recomendaciones: Para la identificación de recomendaciones sustentadas en evidencia y actualizadas, se utilizó la plataforma COVID recmap. Se seleccionaron aquellas guías con rigor metodológico apropiado según la herramienta AGREE II (> 70%) y se incorporaron sus recomendaciones al informe. RESULTADOS: Se identificaron tres revisiones sistemáticas que cumplen con los criterios de inclusión del presente informe. Se identificaron 11 ECA que incluyeron 6620 participantes en los que tocilizumab se comparó con la atención estándar u otros tratamentos. CONCLUSIONES: El cuerpo de evidencia disponible muestra que tocilizumab probablemente se asocia con beneficios en desenlaces críticos como mortalidad e ingreso en asistencia ventilatoria mecánica, sin un incremento sustancial en el riesgo de eventos adversos severos. La certeza global en los efectos de tocilizumab sobre la salud de pacientes con COVID-19 es moderada por imprecisión. Tocilizumab se encuentra disponible en Argentina para el tratamiento de enfermedades reumatológicas, pero no se encuentra aprobado por ANMAT para su uso en pacientes con COVID-19. Se identificaron barreras mayores para su implementación en el contexto de nuestro país, que implicarían tanto la dificultad en la provisión y distribución en un contexto de alta demanda, como así también un costo comparativo muy elevado. Las guías de práctica clínica basadas en evidencia relevadas entregan recomendaciones condicionales y discordantes en cuanto a su uso en pacientes con COVID-19 severo o crítico. Sin embargo, las potenciales barreras relacionadas con dificultades en el suministro apropiado y costos muy elevados podrían afectar su distribución equitativa. Ninguno de los documentos aborda el uso de tocilizumab en pacientes ambulatorios o con enfermedad no severa.


Subject(s)
Humans , SARS Virus/drug effects , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Severity of Illness Index , Cost-Benefit Analysis , Antibodies, Monoclonal, Humanized/economics , Therapeutic Index
18.
Arq. neuropsiquiatr ; 79(4): 305-309, Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1278374

ABSTRACT

ABSTRACT Background: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles. Objective: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America. Methods: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging. Results: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days. Conclusions: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America.


RESUMEN Introducción: A pesar de la abundante información sobre ocrelizumab proveniente de los ensayos clínicos de fase III, todavía se tiene poca evidencia sobre la efectividad y el perfil de pacientes provenientes de la vida real. Objetivo: Evaluar el perfil clínico y demográfico, la efectividad y la persistencia al tratamiento en pacientes que usaron el ocrelizumab para el tratamiento de esclerosis múltiple (EM) en Latinoamérica. Métodos: Estudio retrospectivo multicéntrico en Argentina, Chile y México. Se analizaron los datos de los pacientes que recibieron ocrelizumab. Se describieron las variables demográficas y clínicas, así como los resultados de efectividad que incluyeron la proporción de pacientes libres de recaídas clínicas, libres de progresión de la discapacidad, libres de nuevas lesiones en la secuencia T2 o T1 con gadolinio durante el seguimiento. Resultados: Se incluyeron 81 pacientes. El fenotipo más frecuente fue EM remitente recurrente (EMRR) en el 64,2% de los pacientes. La edad media fue de 41.3±12 años, y el 51,8% eran mujeres. Un total de 38% tuvo recaídas durante los 12 meses previos al inicio de ocrelizumab, con una tasa anualizada de recaídas media de 1.3±0.6 durante ese período. En el seguimiento a 12 meses, el 75% estuvo libre de recaídas clínicas y el 91%, libre de nuevas lesiones en RM. Tres pacientes interrumpieron el tratamiento durante el seguimiento (3,7%). La persistencia al tratamiento observada durante el primer año de seguimiento fue de 338±24 días. Conclusión: Nuestro estudio está en línea con los datos provenientes de ensayos clínicos aleatorizados previos y estudios recientes del mundo real que describen la efectividad de los perfiles de pacientes y la persistencia al tratamiento con ocrelizumab en pacientes con EM en Latinoamérica.


Subject(s)
Humans , Female , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Argentina , Magnetic Resonance Imaging , Chile , Retrospective Studies , Antibodies, Monoclonal, Humanized , Latin America , Mexico
20.
Clinics ; 76: e2653, 2021. tab, graf
Article in English | LILACS | ID: biblio-1286077

ABSTRACT

This study aimed to estimate the incidence of central nervous system (CNS) metastases in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) treated with trastuzumab. Studies were identified through a literature search of electronic databases. Random-effects meta-analyses were performed to estimate the incidence rate of CNS metastases, trastuzumab therapy duration, and time from trastuzumab therapy to CNS metastasis diagnosis. A meta-analysis of odds ratios was performed to evaluate the significance of a difference in CNS metastasis incidence between patients with and without trastuzumab treatment. Thirty studies (8121 trastuzumab-treated and 3972 control patients) were included. The follow-up duration was 18.9 months (95% confidence interval [CI]: 13.8, 24.1). The trastuzumab treatment duration was 9.0 months (95% CI: 7.0, 11.0). The median interval between the start of trastuzumab therapy and CNS metastasis diagnosis was 12.2 months (95% CI: 9.5, 14.7). The incidence of CNS metastasis after the start of trastuzumab therapy was 22% (95% CI: 16, 27). The incidence of CNS metastases was significantly higher in trastuzumab-treated than in non-trastuzumab-treated patients (odds ratio: 1.39 [95% CI: 1.06, 1.82], p=0.02). The survival time from the start of the study was 23.4 months (95% CI: 19.7, 27.1) in trastuzumab-treated patients and 18.4 months (95% CI: 12.7, 24.1) in patients treated with control regimens. The survival time after the development of CNS metastases in trastuzumab-treated patients was 19.2 months (95% CI: 15.6, 25.9). Approximately 22% of patients with HER2-positive MBC who were treated with trastuzumab developed CNS metastases. However, trastuzumab-treated patients had a longer survival than patients who were not treated with trastuzumab.


Subject(s)
Humans , Female , Breast Neoplasms/drug therapy , Central Nervous System , Incidence , Receptor, ErbB-2 , Antibodies, Monoclonal, Humanized/therapeutic use , Trastuzumab/therapeutic use
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