RESUMEN
BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the United States and Europe. However, data on FL from Latin America are scant. AIMS: This study aims at better understand the clinical features, treatment patterns and outcomes of patients with FL in Chile. Of special interest was to evaluate POD24 as an adverse marker. METHODS AND RESULTS: We collected retrospective data from 722 patients 15 years or older diagnosed with FL and treated in 17 cancer centers in Chile between 2000 and 2019. Time to first treatment (TTFT), progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional-hazard regression models were fitted to investigate prognostic factor. The median age at diagnosis was 62 with a female predominance (63%); 73% of patients had advance stage disease and 68% had bone marrow involvement; 63% had intermediate or high FLIPI scores. The 1-year TTFT rate was 96%, and 30% of patients received chemoimmunotherapy. Adding rituximab to chemotherapy was associated with a higher complete response (69% vs. 60%; p < 0.001) and superior median OS (16 vs. 8 years; p < 0.001). Patients who experience POD24 had an inferior median OS (2.4 vs. 15 years). CONCLUSION: Our study shows a female predominance in patients with FL in Chile and confirms superior response and survival outcomes with adding rituximab to chemotherapy. Our study also confirms a poor OS in patients who experience POD24.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/mortalidad , Linfoma Folicular/patología , Linfoma Folicular/terapia , Femenino , Masculino , Persona de Mediana Edad , Chile/epidemiología , Estudios Retrospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Pronóstico , Tasa de Supervivencia , Inmunoterapia/métodos , Supervivencia sin Progresión , Anciano de 80 o más Años , Adulto JovenRESUMEN
PURPOSE OF REVIEW: This review offers an overview of the most important recent articles on pediatric APS. RECENT FINDINGS: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required.
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Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/complicaciones , Niño , Embarazo , Anticoagulantes/uso terapéutico , Rituximab/uso terapéutico , FemeninoRESUMEN
BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.
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Enfermedad de Raynaud , Reumatología , Esclerodermia Sistémica , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Humanos , Brasil , Reumatología/normas , Enfermedad de Raynaud/tratamiento farmacológico , Sociedades Médicas , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Rituximab/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Úlcera Cutánea/etiología , Antirreumáticos/uso terapéuticoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the response to rituximab (RTX) as treatment for lupus nephritis (LN) in a Latin American Lupus cohort. METHODS: The medical records from LN patients from a single-center cohort spanning between January 2012 and December 2020 were reviewed. Demographic factors (age at diagnosis and baseline, gender), disease duration, previous and concomitant treatments, serum creatinine, and 24-hour proteinuria (24-HP) levels at baseline, and 6th and 12th months were obtained. Complete response (CR) or responder status was defined according to the LUNAR, AURORA-1, and BLISS-LN trials. RESULTS: Thirty-six patients received RTX as induction treatment; 32 (88.9%) were women. Their age at baseline and disease duration were 32.6 (11.7) and 7.6 (6.5) years, respectively. The time between renal biopsy and RTX use was 2.64 (4.41) years. At baseline, serum creatinine and 24-HP levels were 1.5 (1.5) mg/dL and 3.4 (2.8) g, respectively. At months 6 and 12, serum creatinine levels were 1.6 (1.6) and 1.6 (1.5) mg/dL, and 24-HP were 2.2 (2.2) and 1.6 (1.5) g, respectively. According to LUNAR and AURORA-1 criteria, CR at 6th and 12th months were 6/34 (17.6%) and 8/30 (26.7%) and 6/34 (17.6%) and 7/31 (22.6%) patients, respectively. According to BLISS-LN criteria, responders at 6th and 12th months were 9/34 (26.5%) and 10/31 (32.3%) patients, respectively. CONCLUSIONS: CR and responder status were reached in less than one third of LN patients treated with RTX, regardless of the criteria used to define them. However, serum creatinine levels did not increase, and there was a decrease in proteinuria levels during the follow-up.
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Nefritis Lúpica , Rituximab , Humanos , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/diagnóstico , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Femenino , Masculino , Adulto , Perú/epidemiología , Resultado del Tratamiento , Creatinina/sangre , Estudios Retrospectivos , Estudios de Cohortes , Adulto JovenRESUMEN
BACKGROUND: Immunosuppressive therapies as azathioprine (AZA), mycophenolate mofetil (MMF) and rituximab (RTX) are widely prescribed as first-line treatment to prevent relapses in NMOSD. However, the rate of response to these traditional therapies is unknown in Argentina. We aimed to describe and compare treatment failure rates in NMOSD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). METHODS: A retrospective cohort study was conducted in NMOSD patients included in RelevarEM (a nationwide, longitudinal, observational, non-mandatory registry of MS and NMOSD in Argentina). NMOSD patients were defined based on validate diagnostic criteria. Only NMOSD patients who received AZA or MMF for at least 6 months or RTX for at least 1 month were included. Patients who were receiving AZA, MMF, or RTX and then switched to another 1 of these 3 therapies were included if the above-mentioned criteria for each drug were fulfilled. Data on patient demographics, clinical, neuroradiological findings, and treatments administered were collected. Treatment failure was defined as any new attack/relapse that occurred despite immunosuppressive treatment. RESULTS: We included 139 NMOSD patients who were receiving AZA (n = 105), MMF (n = 5) or RTX (n = 29) with a mean follow-up time of 41.3 ± 11.4 months and median of EDSS at treatment initiation of 3. We observed a reduction in the annualized relapse rate from pre-treatment to post-treatment of 51.1 %, 48.4 %, and 79.1 % respectively with a Hazard Risk relative to RTX (95 % CI) of 1.67 (1.34-3.54, p = 0.01) for AZA and 2.01 (1.86-4.43, p = 0.008) for MMF. AZA, MMF and RTX failure was observed in 45/105 (42.8 %), 2/5 (40 %) and 3/29 (10.3 %) patients, respectively. CONCLUSIONS: Treatment failure rates were higher for AZA and MMF than RTX in Argentinean NMOSD patients in a real-world setting. High-efficacy treatment increases the opportunity to prevent attacks of NMOSD.
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Azatioprina , Inmunosupresores , Ácido Micofenólico , Neuromielitis Óptica , Sistema de Registros , Rituximab , Insuficiencia del Tratamiento , Humanos , Neuromielitis Óptica/tratamiento farmacológico , Femenino , Argentina , Adulto , Masculino , Inmunosupresores/uso terapéutico , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Estudios Retrospectivos , Azatioprina/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Estudios LongitudinalesRESUMEN
OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.
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Inmunosupresores , Nefritis Lúpica , Sociedades Médicas , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Brasil , Creatinina/sangre , Proteinuria/diagnóstico , Proteinuria/etiología , Ácido Micofenólico/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Reumatología/normas , Rituximab/uso terapéutico , Biopsia , Ciclofosfamida/uso terapéutico , Leflunamida/uso terapéutico , Glucocorticoides/uso terapéutico , Hidroxicloroquina/uso terapéutico , Azatioprina/uso terapéutico , Inducción de Remisión , Ciclosporina/uso terapéutico , Medicina Basada en la Evidencia , Consenso , Progresión de la Enfermedad , Fallo Renal Crónico , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Factores Inmunológicos , Pénfigo , Rituximab , Pénfigo/tratamiento farmacológico , Pénfigo/patología , Humanos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Resultado del Tratamiento , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , AdultoRESUMEN
INTRODUÇÃO: O LF é um tipo de linfoma não Hodgkin (LNH) que se desenvolve pela produção anormal de linfócitos B. No Brasil, sem considerar os tumores de pele não melanoma, o LNH em homens é o oitavo mais frequente. Para as mulheres, LNH é o nono mais frequente. A resposta do LF ao tratamento de primeira linha é geralmente satisfatória e duradoura; no entanto, em alguns pacientes, o câncer recidiva ou progride após um período variável de inatividade da doença. Transplante alogênico de células- tronco hematopoiéticas (TCTH) tem potencial curativo no LF; no entanto, raramente é empregado, pois muitos pacientes são inelegíveis para transplante devido à idade avançada ou indisponibilidade do doador. A quimioimunoterapia com um anticorpo monoclonal anti-CD20 (rituximabe) associado à quimioterapia (ciclofosfamida, doxorrubicina, vincristina, prednisona (CHOP) ou bendamustina) tornou-se uma recomendação mundial para os pacientes com LF que progrediram ao tratamento de primeira linha ou recidivaram. No entanto, a quimioimunoterapia pode n
Asunto(s)
Humanos , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Lenalidomida/uso terapéutico , Sistema Único de Salud , Brasil , Eficacia , Análisis Costo-Beneficio/economía , Combinación de MedicamentosRESUMEN
INTRODUÇÃO: O linfoma folicular (LF) é um tipo de linfoma não Hodgkin (NHL) que se desenvolve quando o corpo produz linfócitos B anormais. No Brasil, sem considerar os tumores de pele não melanoma, o linfoma não Hodgkin em homens é o oitavo mais frequente (2,9%). Para as mulheres, linfoma não Hodgkin é o nono mais frequente (2,4%). Dados de estudos retrospectivos em pacientes assintomáticos com linfoma de baixo grau em estágio avançado não mostraram redução na sobrevida global quando o tratamento sistêmico foi adiado até o desenvolvimento de sintomas ou falência de órgãos, que geralmente ocorreu cerca de 30 meses após o diagnóstico. Esses achados foram subsequentemente confirmados através de estudos randomizados e os resultados observados apoiam a estratégia amplamente praticada de 'espera vigilante'. O rituximabe é um anticorpo monoclonal quimérico dirigido contra o CD20. Quando usado isoladamente em pacientes não tratados previamente com LF de baixa carga tumoral, 80% dos pacientes apresentaram uma resposta (52% resposta completa ou resposta completa não confirmada e 28% resposta parcial) e 48% dos pacientes avaliados alcançaram uma remissão molecular completa após apenas quatro infusões semanais. O rituximabe apresenta um perfil favorável de efeitos colaterais, o que permite considerar seu uso em pacientes assintomáticos. Assim, o objetivo do presente relatório é analisar as evidências científicas sobre eficácia, segurança, bem como evidências econômicas referentes a uma possível incorporação do rituximabe em monoterapia para o tratamento de pacientes com LF assintomático, independentemente do estádio inicial. PERGUNTA: Em pacientes com linfoma folicular assintomático, independentemente do estádio inicial (sem critérios de tratamento imediato), o rituximabe em monoterapia é eficaz, seguro, custo-efetivo e viável economicamente quando comparado com a espera vigilante? EVIDÊNCIAS CLÍNICAS: Foi incluído um ensaio clínico randomizado (ECR) no qual foram comparadas três condutas, a saber, tratamento de indução com rituximabe (RTX); manutenção com RTX e espera vigilante. Três anos após o início da inscrição, o recrutamento para o grupo de indução com rituximabe foi encerrado porque outros estudos mostraram um benefício da manutenção do rituximabe em comparação com a espera vigilante após a indução com rituximabe com ou sem quimioterapia. O desenho do estudo foi revisado, mantendo-se dois dos três braços (espera vigilante versus manutenção com rituximabe). AVALIAÇÃO ECONÔMICA (AE): Foi realizada uma análise de sobrevida particionada com horizonte temporal de 40 anos (lifetime), considerando os estados de saúde pré e pósprogressão e morte, construída a partir dos dados de SG e SLP do ECR identificado. A indução e manutenção com rituximabe se apresentaram como intervenções dominantes, reduzindo os custos relacionados com a progressão da doença e com benefício incremental em termos de anos de vida ajustados pela qualidade (AVAQ) (0,34 e 0,71 AVAQ, respectivamente) quando comparado à espera vigilante. ANÁLISE DE IMPACTO ORÇAMENTÁRIO (AIO): A população elegível foi estimada pelo método de demanda epidemiológica. Os custos considerados foram os relacionados ao tratamento medicamentoso e aos cuidados com a doença nos estágios pré- e pósprogressão. A incorporação de rituximabe pode aumentar o orçamento ao longo de cinco anos em R$ 110.517 num cenário onde apenas a terapia de indução estaria disponível e de R$ 883.461 num cenário onde tanto a terapia de indução quanto terapia de manutenção estariam disponíveis. PERSPECTIVA DO PACIENTE: Foi aberta a Chamada Pública n. 3 de 2024 no período de 29 de janeiro a 7 de fevereiro do mesmo ano e quatro pessoas se inscreveram. A definição dos representantes titular e suplente foi realizada por sorteio em plataforma digital, com transmissão em tempo real e acessível a todos os inscritos. No relato, a representante de associação de pacientes apresentou dois relatos de pacientes: a primeira realizou quimioterapia com R-CHOP e teve prescrição de uso do rituximabe para manutenção do tratamento, mas ainda está aguardando o acesso por via judicial; a segunda teve indicação de uso do medicamento como primeira opção de tratamento e, após utilizá-lo por quatro semanas, a doença entrou em remissão. RECOMENDAÇÕES DE AGÊNCIAS INTERNACIONAIS DE ATS: Foi encontrada uma avaliação do rituximabe em monoterapia para o tratamento de indivíduos com LF assintomático, independentemente do estádio inicial no NICE (Inglaterra). Nenhuma avaliação da tecnologia foi encontrada no SMC (Escócia), CADTH (Canadá) e PBAC (Austrália). O NICE (Reino Unido) recomenda a terapia de indução com rituximabe para pessoas com LF em estágio avançado (estágios III e IV) que são assintomáticos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Uma tecnologia foi detectada para compor o tratamento do linfoma folicular, independentemente do estádio inicial, sem sintomas e sem critérios de tratamento imediato. O medicamento odronextamab é um anticorpo monoclonal anti-CD20, sem registro sanitário ou avaliação de ATS. Não foram identificados resultados para os ensaios clínicos em andamento. CONSIDERAÇÕES FINAIS: A partir da avaliação dos resultados concluiu-se que em pacientes com LF assintomático em estágio avançado de baixa carga tumoral, a SLP, após o uso do rituximabe de manutenção, foi significativamente maior do que a observada nos grupos que receberam a conduta da espera vigilante ou tratamento de indução com rituximabe sem manutenção. As avaliações econômicas demonstraram que a indução com rituximabe foi dominante e a sua incorporação aumentaria o orçamento ao longo de cinco anos em R$ 110.517 (apenas terapia de indução) até R$ 883.461 (terapia de indução e terapia de manutenção). Cabe destacar que, nas avaliações econômicas, foram considerados os resultados do ensaio clínico para os desfechos de SG e SLP; e que há controversas na literatura e na prática clínica sobre a introdução da terapia sistêmica para pacientes com LF assintomáticos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Medicamentos presentes na 127ª Reunião da Conitec, realizada no dia 07 de março de 2024, deliberaram que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à incorporação ao SUS do rituximabe em monoterapia para pacientes com LF assintomáticos, independentemente do estádio inicial (sem critérios de tratamento imediato). Apesar das evidências apresentadas e do potencial benefício em termos de sobrevida livre de progressão, discutiu-se que a recomendação de tratamento para pacientes assintomáticos ainda é controversa na prática clínica e entre as diretrizes internacionais, e que se deve considerar, sobretudo, os riscos e benefícios do tratamento sistêmico precoce. Além disso, as evidências demonstraram não haver benefícios na sobrevida global e com resultados limitados na melhora da qualidade de vida, ao passo que a sobrevida livre de progressão pode não ser um desfecho prioritário para decisão de tratamento no contexto do linfoma folicular, tendo em vista a sua natureza semiobjetiva. CONSULTA PÚBLICA: A Consulta Pública nº 15 foi realizada entre os dias 09 e 29 de abril de 2024, recebendo o total de 107 contribuições. Todas foram submetidas à análise de conteúdo temática. Das 107 contribuições recebidas, 106 foram desfavoráveis à recomendação inicial da Conitec de não incorporação do medicamento no SUS e uma foi a favor da recomendação. Os argumentos favoráveis à incorporação do rituximabe em monoterapia para pacientes com linfoma folicular assintomático contemplavam os efeitos positivos, tais como a remissão da doença e a qualidade de vida. Os participantes relataram, como principal ponto negativo, a dificuldade de acesso ao medicamento, o alto custo e alguns eventos adversos, em sua maioria considerados esperados e leves. Foram identificadas 98 (91,6%) contribuições vazias para as evidências clínicas e 98 (91,6%) para estudos econômicos. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Medicamentos da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde Conitec, presentes na 130ª reunião ordinária, no dia 6 de junho de 2024, deliberaram, por unanimidade, recomendar a não incorporação do rituximabe em monoterapia para pacientes com LF assintomático, independente do estádio inicial. Considerou-se que não houve adição de informações relevantes para modificar o entendimento inicial de que as evidências científicas de benefício do medicamento são limitadas e que não há consenso entre especialistas sobre o tratamento do linfoma folicular na fase assintomática. Foi assinado o Registro de Deliberação nº 903/2024. DECISÃO: não incorporar, no âmbito do Sistema Único de Saúde - SUS, o rituximabe em monoterapia para pacientes com linfoma folicular assintomático, independentemente do estádio inicial, publicada no Diário Oficial da União nº 142, seção 1, página 73, em 25 de julho de 2024.
Asunto(s)
Humanos , Portador Sano , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Sistema Único de Salud , Brasil , Eficacia , Análisis Costo-Beneficio/economíaRESUMEN
OBJECTIVES: To describe the response and relapse of severe thrombocytopenia in patients with systemic lupus erythematosus (SLE) with different treatments. METHOD: We performed a retrospective cohort study, which included SLE patients who were hospitalized for thrombocytopenia of less than 30,000/µL platelets, from January 2012 to December 2021. Demographic and clinical information was obtained from clinical records. Kaplan-Meier and logrank test were performed. RESULTS: Forty-seven patients, mostly women (83%) with a median age of 31 years, were included in the study. Eight patients (17%) relapsed within a median period of 35.7 weeks. Initial acute treatment with prednisone at 1 mg/kg/day was as effective as glucocorticoid pulses. However, induction treatment with cyclophosphamide (CYC) had the lowest remission rate (43%, p = 0.034). There was no significant difference in relapse-free survival (RFS) among the acute glucocorticoid treatments. CYC induction was associated with lower RFS compared to rituximab (RTX) (CYC 43.6 weeks vs. RTX 51.8 weeks, p = 0.040) or azathioprine (AZA) (CYC 43.6 weeks vs. AZA 51.2 weeks, p = 0.024). Administration of antimalarials was associated with longer RFS (51.6 weeks vs. 45.0 weeks, p = 0.021). Factors such as antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, renal and additional hematologic SLE activity during follow-up significantly reduced RFS. CONCLUSIONS: Despite similar response of acute glucocorticoid regimens, induction therapy with AZA or RTX resulted in a longer RFS compared to CYC. Adding an antimalarial also improved RFS. Our study provides evidence that may help develop better treatment strategies for severe thrombocytopenia in SLE patients. Key Points ⢠Induction therapy with azathioprine or rituximab provided longer relapse-free survival in SLE thrombocytopenia compared with cyclophosphamide. ⢠Antimalarial administration was associated with longer relapse-free survival in SLE thrombocytopenia. ⢠Antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, as well as renal and additional hematologic SLE activity during follow-up, decreased relapse-free survival.
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Azatioprina , Ciclofosfamida , Glucocorticoides , Inmunosupresores , Lupus Eritematoso Sistémico , Recurrencia , Rituximab , Humanos , Femenino , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Masculino , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico , Glucocorticoides/uso terapéutico , Azatioprina/uso terapéutico , Inmunosupresores/uso terapéutico , Antimaláricos/uso terapéutico , Persona de Mediana Edad , Prednisona/uso terapéutico , Adulto Joven , Resultado del Tratamiento , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/complicaciones , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/etiologíaRESUMEN
In rare instances, patients with SLE may exhibit atypical clinical manifestations, such as Hypocomplementemic Urticarial Vasculitis, which can pose diagnostic challenges. Here, we present a case report of a 28-year-old female with a history of SLE with lupus nephritis clase IV who developed HUV-like symptoms, ultimately leading to a diagnosis of C1q Vasculitis. This case underscores the importance of considering C1q Vasculitis in SLE patients presenting with HUV-like features and highlights Rituximab as a promising therapeutic option for managing this rare condition.
Asunto(s)
Complemento C1q , Lupus Eritematoso Sistémico , Rituximab , Urticaria , Vasculitis , Humanos , Femenino , Adulto , Complemento C1q/deficiencia , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológico , Urticaria/diagnóstico , Rituximab/uso terapéutico , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/complicaciones , Nefritis Lúpica/tratamiento farmacológico , Diagnóstico DiferencialRESUMEN
PURPOSE: Metabolic syndrome (MetS), characterized by insulin resistance, is closely associated with the prognosis of various cancer types, but has not been reported in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to examine how other clinicopathological variables and the MetS influence the prognosis of DLBCL. METHODS: Clinical and pathological data were collected from 319 patients with DLBCL who were admitted to our hospital between January 2012 and December 2020. The data accessible with SPSS 27.0 enables the utilization of various statistical methods for clinical data analysis, including independent sample t test and univariate and multivariate COX regression. RESULTS: The presence of MetS was linked to both overall survival (OS) and progression-free survival (PFS), in addition to other clinicopathological characteristics as age, IPI score, rituximab usage, and Ki-67 expression level. This link with OS and PFS indicated a poor prognosis, as shown by survival analysis. Subsequent univariate analysis identified IPI score, Ki-67 expression level, tumor staging, rituximab usage, lactate dehydrogenase expression level, and the presence or absence of MetS as factors linked with OS and PFS. Furthermore, multivariate Cox regression analysis confirmed the independent risk factor status of IPI score, Ki-67 expression level, rituximab usage, and the presence of MetS in evaluating the prognosis of patients with DLBCL. CONCLUSION: This study's findings indicate that patients with pre-treatment MetS had a poor prognosis, with relatively shorter OS and PFS compared to those without pre-treatment MetS. Furthermore, the presence of MetS, IPI score, Ki-67 expression level, and rituximab usage were identified as independent risk factors significantly affecting the prognosis of DLBCL.
Asunto(s)
Linfoma de Células B Grandes Difuso , Síndrome Metabólico , Rituximab , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Síndrome Metabólico/complicaciones , Pronóstico , Anciano , Rituximab/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más Años , Doxorrubicina/uso terapéutico , Factores de Riesgo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Supervivencia sin Progresión , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Tasa de Supervivencia , Estadificación de Neoplasias , Adulto Joven , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Modelos de Riesgos ProporcionalesRESUMEN
Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) are typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, a standard of care for managing adolescents and young adults (AYAs) with DLBCL is lacking. We examine treatment approaches and outcomes of this population. Methods: We included 90 AYAs (15-39 years) diagnosed with DLBCL between 2008 and 2018 in three tertiary centers in Peru. Overall response rates (ORR) were available for all patients. Overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. Results: The median age at diagnosis was 33 years, 57% were males, 57% had good performance status (Lansky/Karnofsky ≥90), and 61% were diagnosed with early-stage disease (Ann Arbor stages I-II). R-CHOP (n = 69, 77%) was the most frequently used first-line regimen, with an ORR of 91%. With a median follow-up of 83 months, the 5-year OS and PFS among all patients were 79% and 67%, respectively. Among the patients who received R-CHOP, the 5-year OS and PFS were 77% and 66%, respectively. Of the 29 (32%) patients with relapsed/refractory (R/R) disease, 83% received second-line treatment and only 14% underwent consolidation therapy with autologous transplantation. The 3-year OS for R/R DLBCL was 36%. Conclusion: Our data show that AYAs with DLBCL who received conventional therapy had comparable outcomes to those observed in studies conducted among the adult population. However, the prognosis for AYAs with R/R disease was dismal, indicating the unmet need for developing and increasing access to novel treatment modalities in AYAs.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Masculino , Humanos , Adulto Joven , Adolescente , Adulto , Femenino , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Rituximab/uso terapéutico , Pronóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológicoRESUMEN
OBJECTIVE: The objective of this study was to assess the SARS-CoV-2-specific humoral and T cell response after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: In this observational study, patients with RA who are ≥18 years of age and vaccinated for SARS-CoV-2 according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies (ELISA-COVIDAR test), neutralizing activity (cytotoxicity in VERO cells), and specific T cell response (IFN-γ ELISpot Assay) were assessed after the first and second dose. RESULTS: A total of 120 patients with RA were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), and BBIBP-CorV (22.5%). The most frequent combination was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose, 81.7% presented with anti-SARS-CoV-2 antibodies, 70.0% presented with neutralizing activity, and 65.3% presented with specific T cell response. The use of BBIBP-CorV and treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses. BBIBP-CorV was also associated with the absence of T cell response. The total incidence of adverse events was 357.1 events per 1,000 doses, significantly lower with BBIBP-CorV (166.7 events per 1,000 doses, P < 0.02). CONCLUSION: In this RA cohort vaccinated with homologous and heterologous regimens against COVID-19, 2 out of 10 patients did not develop anti-SARS-CoV-2 IgG, 70% presented with neutralizing activity, and 65% presented with specific T cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, whereas treatment with ABA and RTX resulted in an impaired anti-SARS-CoV-2 IgG formation and neutralizing activity.
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Artritis Reumatoide , COVID-19 , Chlorocebus aethiops , Animales , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Células Vero , COVID-19/prevención & control , Linfocitos T , Artritis Reumatoide/tratamiento farmacológico , Abatacept , Rituximab , Vacunación , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity. Currently, there is a paucity of randomized prospective data to inform on optimal front-line chemoimmunotherapy (CIT) and use of consolidative mediastinal radiation (RT). To assess if distinct CIT approaches are associated with disparate survival outcomes, we performed a systematic review and meta-analysis comparing dose-intensive (DI-CIT) versus standard CIT for the front-line treatment of PMBCL. Standard approach (S-CIT) was defined as R-CHOP-21/CHOP-21, with or without RT. DI-CIT were defined as regimens with increased frequency, dose, and/or number of systemic agents. We reviewed data on 4,068 patients (2,517 DI-CIT; 1,551 S-CIT) with a new diagnosis of PMBCL. Overall survival for DI-CIT patients was 88% (95% CI: 85-90) compared to 80% for the S-CIT cohort (95% CI: 74-85). Meta-regression revealed an 8% overall survival (OS) benefit for the DI-CIT group (P<0.01). Survival benefit was maintained when analyzing rituximab only regimens; OS was 91% (95% CI: 89-93) for the rituximab-DI-CIT arm compared to 86% (95% CI: 82-89) for the R-CHOP-21 arm (P=0.03). Importantly, 55% (95% CI: 43-65) of the S-CIT group received RT compared to 22% (95% CI: 15-31) of DI-CIT patients (meta-regression P<0.01). To our knowledge, this is the largest meta-analysis reporting efficacy outcomes for the front-line treatment of PMBCL. DI-CIT demonstrates a survival benefit, with significantly less radiation exposure, curtailing long-term toxicities associated with radiotherapy. As we await results of randomized prospective trials, our study supports the use of dose-intensive chemoimmunotherapy for the treatment of PMBCL.
Asunto(s)
Linfoma de Células B , Exposición a la Radiación , Humanos , Estudios Prospectivos , Rituximab/uso terapéutico , Linfocitos B , Linfoma de Células B/tratamiento farmacológicoAsunto(s)
Enfermedades Autoinmunes , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Adulto , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéuticoRESUMEN
Introduction: Rituximab is an Anti-CD20 chimeric monoclonal antibody, being the treatment of lymphoproliferative diseases and rheumatological disorders; hypersensitivity reactions (HRS) are associated with infusion, cytokine release, type I (IgE/non-IgE), mixed, type III and IV. Desensitization seeks to induce tem- porary tolerance, decreasing the probability of clinical manifestations through gradual administration of the total dose of the drug, being target cells of the procedure, basophils, and mast cells, preventing their activation. Case report: The objective is to present a personalized desensitization protocol in a 36-year-old female patient with systemic lupus erythematosus (SLE) pre- viously treated with rituximab in 2019, 4 doses, presenting during the fourth administration, after 10 minutes, dyspnea, feeling foreign body in the pharynx, chest pain, angioedema, and neurological alteration. Requiring new administration of rituximab due to persistent proteinuria secondary to SLE. After performing skin tests (negative), a 13-step desensitization scheme was performed with 3 concentrations (solution: A [1:100], B [1:10] and C [1:1]). Since only 52% of RHS to rituximab are positive in skin tests and given the degree of reaction (serious), desensitization is decided, based on reactions presented by patient and clinical context. Achieving a cumulative dose of 897.87 mg in a period of 5 hours, without reactions during or after the procedure, concluding successfully. Conclusion: By carrying out desensitization protocols, the administration of a drug is allowed, offering a safe therapeutic option, when this is the treatment of choice in previously sensitized patients, offering an alternative when the benefits outweigh the risks of its administration.
Introducción: El rituximab es un anticuerpo monoclonal quimérico Anti-CD20, siendo tratamiento de enfermedades linfoproliferativas y trastornos reumatológi- cos; las reacciones de hipersensibilidad (RHS) se asocian con la infusión, liberación de citocinas, tipo I (IgE/no-IgE), mixtas, tipo III y IV. La desensibilización busca inducir tolerancia temporal disminuyendo probabilidad de manifestaciones clínicas mediante administración gradual de dosis total del medicamento, siendo células blanco del procedimiento, basófilos y mastocitos, previniendo su activación. Reporte de caso: El objetivo es presentar un protocolo de desensibilización personalizado en paciente femenino de 36 años, con Lupus eritematoso sistémico (LES) tratada previamente con rituximab en 2019, 4 dosis, presentando durante cuarta administración, a los 10 minutos, disnea, sensación de cuerpo extraño en faringe, dolor torácico, angioedema y alteración neurológica. Requiriendo nueva administración de rituximab por proteinuria persistente secundario a LES. Previa realización de pruebas cutáneas (negativas), se realiza esquema de desensibilización de 13 pasos con 3 concentraciones (solución: A [1:100], B [1:10] y C [1:1]). Ya que sólo 52% de RHS a rituximab resultan positivas en pruebas cutáneas y ante grado de reacción (grave), se decide desensibilización, basado en reacciones presentadas por paciente y contexto clínico. Logrando llegar a dosis acumulada de 897.87 mg en un periodo de 5 horas, sin reacciones durante ni posterior a procedimiento, concluyéndose exitosamente. Conclusión: Mediante realización de protocolos de desensibilización se permite administración de un medicamento, ofreciendo una opción terapéutica segura, cuando éste es tratamiento de elección en pacientes sensibilizados previamente, ofreciendo una alternativa cuando los beneficios superan los riesgos de su administración.
Asunto(s)
Antineoplásicos , Lupus Eritematoso Sistémico , Femenino , Humanos , Adulto , Rituximab/efectos adversos , Antineoplásicos/efectos adversos , Citocinas , Desensibilización Inmunológica/métodosRESUMEN
BACKGROUND Non-Hodgkin lymphoma is the most common hematological malignancy in the world. Diffuse large B-cell lymphoma the most common type and the cutaneous involvement due to this neoplasm is rare. Some risk factors, such as exposure to pesticides, alcohol consumption, and tobacco use, are well established. Over the past 10 years, the association between clozapine, which is the criterion standard treatment for refractory schizophrenia, and hematological malignancies has been described. CASE REPORT We report a case of a 44-year-old woman diagnosed with schizophrenia 31 years previously, who had been taking clozapine since 2009, presenting with diffuse cutaneous nodules and subcutaneous masses accompanied by asthenia, dry cough, and a weight loss of 12 kg. Computed tomography revealed multiple enlarged lymph nodes on both sides of the diaphragm, in addition to multiple large subcutaneous masses located on the right flank and on the right upper lateral chest wall (infra-axillary), homogeneous splenomegaly, and heterogeneous nodular areas of hypoenhancement, poorly delimited, in both kidneys. Diffuse large B-cell lymphoma in an advanced stage (IVBX) was diagnosed by skin biopsy, with extranodal involvement. Chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days) was performed and the decision to maintain clozapine was made. At 1.5 years after the initial diagnosis the patient presented with relapse of the disease and is in follow-up. CONCLUSIONS This case report suggests the potential association between clozapine and an increased risk of lymphoma, with a few case reports in the literature reinforcing this association. Additional studies are required to either confirm or dismiss this association, and new guidelines are needed to define the safety and monitoring of the long-term usage of clozapine.