RESUMO

INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

RESUMO

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.

Assuntos

Azatioprina , Ciclofosfamida , Glucocorticoides , Imunossupressores , Lúpus Eritematoso Sistêmico , Recidiva , Rituximab , Humanos , Feminino , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Masculino , Ciclofosfamida/uso terapêutico , Rituximab/uso terapêutico , Glucocorticoides/uso terapêutico , Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Antimaláricos/uso terapêutico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Adulto Jovem , Resultado do Tratamento , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/complicações , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia

RESUMO

Desde el inicio de la pandemia por COVID-19 (coronavirus disease), en el 2019, se han descrito numerosas manifestaciones clínicas de la enfermedad causada por este virus, destacando el compromiso respiratorio, hematológico, cardiovascular y neurológico. Dentro de las manifestaciones y/o complicaciones neurológicas, se encuentra la mielitis aguda transversa por COVID-19(1), cuyo diagnóstico se ha realizado principalmente clínico-imagenológico y PCR (reacción de polimerasa en cadena), o serología (+) para COVID-19, con manejos y resultados no siempre afortunados. Presentamos el caso de un paciente con mielitis aguda transversa longitudinalmente extensa en relación a COVID-19, tratada con éxito clínico con rituximab.

---

Since the beginning of the COVID-19 pandemic in 2019, numerous clinical manifestations of the disease caused by this virus have been described, highlighting respiratory, hematological, cardiovascular, and neurological compromise. Among the neurological manifestations and/or complications, there is acute transverse myelitis due to COVID-19(1), whose diagnosis has been made mainly clinical-imaging and PCR or serology (+) for COVID-19, with management and results not always lucky. We present the case of a patient with longitudinally extensive acute transverse myelitis in relation to COVID-19, treated with clinical success with rituximab.

RESUMO

ABSTRACT Introduction: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. Methods: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. Results: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. Conclusion: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

Assuntos

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma não Hodgkin , Sistema Nervoso Central , Linfoma

RESUMO

Abstract Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. Objective With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. Methods A total of 25 panelists, including adult and child neurologists, participated in the study. Results The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Conclusion The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.

---

Resumo Antecedentes Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. Objetivo Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. Métodos Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. Resultados Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Conclusão Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.

RESUMO

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.

Assuntos

Antineoplásicos , Lúpus Eritematoso Sistêmico , Feminino , Humanos , Adulto , Rituximab/efeitos adversos , Antineoplásicos/efeitos adversos , Citocinas , Dessensibilização Imunológica/métodos

RESUMO

ABSTRACT Introduction: Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. Method: A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. Results: Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. Conclusion: Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.

---

Resumo Introdução: Rituximabe (RTX) é uma opção terapêutica na síndrome nefrótica (SN) idiopática pediátrica de difícil tratamento. Visamos avaliar eficácia e segurança do uso de RTX nestes pacientes. Método: Realizou-se estudo retrospectivo de todos os pacientes com SN idiopática tratados com RTX, em uma unidade de nefrologia pediátrica de um hospital terciário. Dados demográficos, antropométricos, clínicos e analíticos foram coletados antes do tratamento e aos 6, 12 e 24 meses. Resultados: Incluímos 16 pacientes (11 do sexo masculino), com idade mediana (percentil 25-75, P25-P75) de 2 (2,0-2,8) anos ao diagnóstico. Quinze eram sensíveis a esteroides, e 1 resistente a esteroides e sensível à ciclosporina.A idade mediana na administração do RTX foi 10 (6,3-14,0) anos. Durante um tempo mediano de acompanhamento de 2,5(1,0-3,0) anos, 6 (37,5%) pacientes alcançaram remissão parcial e 7 (43,8%) não tiveram recidivas e não estavam tomando imunossupressor no acompanhamento aos 24 meses. Quanto às complicações,1 paciente apresentou hipogamaglobulinemia persistente. Comparado ao período de12 meses anterior ao RTX, houve diminuição no número mediano de recidivas em 6 e 12 meses [3 (3,0-4,0) vs 0 (0-0,8) e 0,50 (0-1,0), respectivamente; p = 0,001] e na dose diária de esteroides (mg/kg/dia) aos 6, 12 e 24 meses [0,29 (0,15-0,67) >vs [0,10 (0,07-0,13); p = 0,001], [0,12 (0,05-0,22); p = 0,005] e [0,07 (0,04-0,18); p = 0,021], respectivamente. Houve também redução na mediana do escore z do IMC aos 24 meses [2,11 (0,45-3,70) vs 2,93 (2,01-3,98);p = 0,049]. Conclusões: Nossos resultados confirmam a eficácia e segurança do uso de RTX em SN idiopática pediátrica, destacando seus potenciais benefícios cardiometabólicos.

RESUMO

Secondary immunodeficiency can result from neoplasms, infections, or immunosuppressive therapy. Rituximab (RTX) is an anti-CD20 antibody that depletes B lymphocytes and can induce symptomatic hypogammaglobulinemia. We report 3 cases of symptomatic hypogammaglobulinemia associated with the use of RTX. In patient 1 with rheumatoid arthritis, RTX induced low levels of immunoglobulins and recurrent airway infections. RTX discontinuation led to a normalization of the humoral immune response. Patients 2 and 3, treated with RTX for non-Hodgkin lymphoma and systemic lupus erythematosus, respectively, developed persistent secondary hypogammaglobulinemia requiring immunoglobulin replacement therapy for years. After RTX discontinuation, patients may experience rapid recovery of humoral function or remain with low serum immunoglobulin levels for extended periods. With the increasing use of therapies targeting components of the immune system, a high degree of clinical suspicion for the development of secondary immunodeficiency may minimize the morbidity and mortality associated with these therapies.

---

As imunodeficiências secundárias podem ser uma consequência de neoplasias, infecções ou tratamentos imunossupressores. O rituximabe (RTX) é um anticorpo anti-CD20 que depleta os linfócitos B e pode induzir uma hipogamaglobulinemia sintomática. Aqui, relatamos três casos de hipogamaglobulinemia sintomática associada ao uso de RTX. Na primeira paciente com artrite reumatoide, o RTX induziu a baixos níveis de imunoglobulinas associadas a infecções de vias aéreas de repetição. Após a suspensão do RTX, houve normalização da resposta imune humoral. Os outros dois casos, com o uso de RTX para tratamento de linfoma não-Hodgkin e lúpus eritematoso sistêmico, respectivamente, as pacientes evoluíram com hipogamaglobulinemia secundária persistente, com necessidade de reposição de imunoglobulina por vários anos. Pacientes tratados com RTX podem apresentar, após a sua suspensão, uma recuperação rápida da função humoral ou permanecerem com baixos níveis séricos de imunoglobulinas por longos períodos. Com o crescente uso dos tratamentos direcionados para componentes do sistema imunológico, um alto grau de suspeição clínica para o aparecimento de imunodeficiências secundárias pode minimizar a morbimortalidade associada a estes tratamentos.

Assuntos

Humanos , Feminino , Adulto , Pessoa de Meia-Idade

RESUMO

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

Assuntos

Antirreumáticos , Artrite Reumatoide , Humanos , Abatacepte/uso terapêutico , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antirreumáticos/uso terapêutico , Metanálise em Rede , Artrite Reumatoide/tratamento farmacológico

RESUMO

Primary penile lymphomas are extremely rare. They are aggressive neoplasms that can present as double-or triple-hit lymphomas, and because the associate with a high risk of central nervous system dissemination, treatment consists of high-dose chemotherapy regimens plus intrathecal prophylaxis. Pathology can be confused with squamous cell carcinoma of the penis, leading to inappropriate treatments and unnecessary amputations. We report the case of a patient diagnosed with clinical Stage IV penile non-Hodgkin lymphoma that was treated with a complete and durable response. In addition, we review the available literature on penile lymphoma.

Assuntos

Linfoma não Hodgkin , Linfoma , Masculino , Humanos , Rituximab/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Pênis/cirurgia , Pênis/patologia

RESUMO

BACKGROUND: Multiple sclerosis is a chronic, autoimmune, degenerative disease. Therapies targeting B-cells have been shown to be effective in its treatment; however, there are few studies evaluating their efficacy in the Mexican population. OBJECTIVE: To evaluate the clinical impact of rituximab in patients with newly-diagnosed relapsing-remitting multiple sclerosis (RRMS). MATERIAL AND METHODS: Real life, descriptive study, in which rituximab was evaluated as treatment for RRMS over a 24-month period. Pre- and post-treatment clinical variables were analyzed; a comparison was made between treatment-naïve and non-treatment-naïve patients. RESULTS: Twenty-eight patients with RRMS were included. Mean age at diagnosis was 30.7 years, and 22 patients were treatment-naïve (78.5 %). After 24 months, there was a mean reduction of 1.8 points in the EDSS scale and a decrease in the number of active lesions on magnetic resonance imaging; a significant difference in both variables could be established (p < 0.05). However, the logistic regression model did not show a relationship between the variables for achieving NEDA-3 criteria. No serious adverse events were observed. CONCLUSIONS: Treatment with rituximab resulted in significant clinical and radiological improvement in treatment-naïve and non-treatment-naïve Mexican patients with RRMS.

---

ANTECEDENTES: La esclerosis múltiple es una enfermedad crónica, autoinmune y degenerativa. Las terapias blanco contra los linfocitos B han probado ser efectivas en su tratamiento; sin embargo, existen pocos estudios que evalúen su eficacia en población mexicana. OBJETIVO: Evaluar el impacto clínico del rituximab en pacientes con esclerosis múltiple remitente recurrente (EMRR) de reciente diagnóstico. MATERIAL Y MÉTODOS: Estudio de vida real, descriptivo, en el que se evalúa rituximab como tratamiento de EMRR durante un periodo de 24 meses. Se analizaron variables clínicas pre y postratamiento; se realizó la comparación entre pacientes naïve y no naïve. RESULTADOS: Se incluyeron 28 pacientes con EMRR. La edad media al diagnóstico fue de 30.7 años y 22 pacientes fueron naïve (78.5 %). Después de 24 meses, se observó una reducción media de 1.8 puntos en EDSS y en el número de lesiones activas por resonancia magnética. Aunque se logró establecer una diferencia significativa en ambas variables con p < 0.05, el modelo de regresión logística no mostró una relación entre las variables para alcanzar un NEDA-3. No se observaron eventos adversos graves. CONCLUSIONES: El tratamiento con rituximab resultó en mejoría significativa clínica y radiológica en pacientes mexicanos con EMRR naïve y no-naïve.

Assuntos

Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Rituximab/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , México , Centros de Atenção Terciária , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/induzido quimicamente

RESUMO

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

---

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

RESUMO

Resumen Antecedentes: La esclerosis múltiple es una enfermedad crónica, autoinmune y degenerativa. Las terapias blanco contra los linfocitos B han probado ser efectivas en su tratamiento; sin embargo, existen pocos estudios que evalúen su eficacia en población mexicana. Objetivo: Evaluar el impacto clínico del rituximab en pacientes con esclerosis múltiple remitente recurrente (EMRR) de reciente diagnóstico. Material y métodos: Estudio de vida real, descriptivo, en el que se evalúa rituximab como tratamiento de EMRR durante un periodo de 24 meses. Se analizaron variables clínicas pre y postratamiento; se realizó la comparación entre pacientes naïve y no naïve. Resultados: Se incluyeron 28 pacientes con EMRR. La edad media al diagnóstico fue de 30.7 años y 22 pacientes fueron naïve (78.5 %). Después de 24 meses, se observó una reducción media de 1.8 puntos en EDSS y en el número de lesiones activas por resonancia magnética. Aunque se logró establecer una diferencia significativa en ambas variables con p < 0.05, el modelo de regresión logística no mostró una relación entre las variables para alcanzar un NEDA-3. No se observaron eventos adversos graves. Conclusiones: El tratamiento con rituximab resultó en mejoría significativa clínica y radiológica en pacientes mexicanos con EMRR naïve y no-naïve.

---

Abstract Background: Multiple sclerosis is a chronic, autoimmune, degenerative disease. Therapies targeting B-cells have been shown to be effective in its treatment; however, there are few studies evaluating their efficacy in the Mexican population. Objective: To evaluate the clinical impact of rituximab in patients with newly-diagnosed relapsing-remitting multiple sclerosis (RRMS). Material and methods: Real life, descriptive study, in which rituximab was evaluated as treatment for RRMS over a 24-month period. Pre- and post-treatment clinical variables were analyzed; a comparison was made between treatment-naïve and non-treatment-naïve patients. Results: Twenty-eight patients with RRMS were included. Mean age at diagnosis was 30.7 years, and 22 patients were treatment-naïve (78.5 %). After 24 months, there was a mean reduction of 1.8 points in the EDSS scale and a decrease in the number of active lesions on magnetic resonance imaging; a significant difference in both variables could be established (p < 0.05). However, the logistic regression model did not show a relationship between the variables for achieving NEDA-3 criteria. No serious adverse events were observed. Conclusions: Treatment with rituximab resulted in significant clinical and radiological improvement in treatment-naïve and non-treatment-naïve Mexican patients with RRMS.

RESUMO

OBJECTIVE: To describe the prevalence of persistent hypogammaglobulinemia in patients receiving Rituximab as a treatment for autoimmune rheumatological diseases. METHODS: A transversal, retrospective and unicentric study, carried out in patients with autoimmune rheumatic diseases who were admitted to the Rheumatology service of the Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Mexico City, to receive treatment with rituximab between January 2013 and January 2018. Descriptive and inferential statistics of serum levels of immunoglobulins, clinical-demographic characteristics, diagnosis, and treatment received were performed. RESULTS: from 262 patients with autoimmune rheumatological disease who received treatment with Rituximab; We identified 8 patients with persistent hypogammaglobulinemia (6 women and 2 men), this is a prevalence of 3.1%. No associated factors with the development of hypogammaglobulinemia were identified. CONCLUSIONS: Until now, no associated prognostic or predictive factors have been identified with persistent hypogammaglobulinemia. Additional prospective studies are required to understand more precisely the implications of persistent hypogammaglobulinemia in patients with autoimmune diseases.

---

OBJECTIVO: Determinar la prevalencia de hipogammaglobulinemia persistente en pacientes con enfermedades reumatológicas autoinmunes que reciben rituximab. MÉTODOS: Estudio trasversal, retrospectivo y unicéntrico, emprendido en pacientes con enfermedades reumatológicas autoinmunes, que acudieron a la Consulta externa del servicio de Reumatología del Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Ciudad de México, entre enero de 2013 y enero de 2018, para recibir tratamiento con rituximab. El análisis de los datos se efectuó con estadística descriptiva e inferencial, para la evaluación de las concentraciones séricas de inmunoglobulinas, características clínico demográficas, diagnóstico y tratamiento. RESULTADOS: Estudio trasversal, retrospectivo y unicéntrico, emprendido en pacientes con enfermedades reumatológicas autoinmunes, que acudieron a la Consulta externa del servicio de Reumatología del Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Ciudad de México, entre enero de 2013 y enero de 2018, para recibir tratamiento con rituximab. El análisis de los datos se efectuó con estadística descriptiva e inferencial, para la evaluación de las concentraciones séricas de inmunoglobulinas, características clínico demográficas, diagnóstico y tratamiento. CONCLUSIONES: Hasta el momento no se han identificado factores asociados, pronósticos o predictivos, con hipogammaglobulinemia persistente. Se requieren estudios prospectivos adicionales para conocer con mayor precisión las implicaciones de la hipogammaglobulinemia persistente en pacientes con enfermedades autoinmunes.

Assuntos

Agamaglobulinemia , Doenças Autoimunes , Doenças Reumáticas , Masculino , Humanos , Feminino , Rituximab/uso terapêutico , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/etiologia , Estudos Retrospectivos , Prevalência , México/epidemiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Hospitais , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia

RESUMO

OBJECTIVES: This study aimed to determine the cost-utility of ocrelizumab versus rituximab in patients with RRMS, from the perspective of the Colombian healthcare system. METHODOLOGY: Cost-utility study based on a Markov model, with a 50-year horizon and payer perspective. The currency was the US dollar for the year 2019, with a cost-effectiveness threshold of $5180 defined for Colombian health system. The model used annual cycles according to the health status determined by the disability scale. Direct costs were considered, and the incremental cost-effectiveness ratio per 1 quality-adjusted life-year (QALY) gained was used as the outcome measure. A discount rate of 5% was applied to costs and outcomes. Multiple one-way deterministic sensitivity analyses and 10 000 Monte Carlo simulation were conducted. RESULTS: For the treatment of patients with RRMS, ocrelizumab versus rituximab had an incremental cost-effectiveness ratio of $73 652 for each QALY gained. After 50 years, 1 subject treated with ocrelizumab earns 4.8 QALYs >1 subject treated with rituximab, but at a higher cost of $521 759 versus $168 752, respectively. Ocrelizumab becomes a cost-effective therapy if its price is discounted > 86% or if there is a high willingness to pay. CONCLUSIONS: Ocrelizumab was not a cost-effective drug as compared with rituximab in treating patients with RRMS in Colombia.

Assuntos

Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Análise Custo-Benefício , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Colômbia , Esclerose Múltipla/tratamento farmacológico

RESUMO

INTRODUCTION: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. METHODS: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. RESULTS: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. CONCLUSION: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

RESUMO

RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.

---

ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.

Assuntos

Azatioprina , Rituximab , Recidiva , Neuromielite Óptica

RESUMO

Introducción . El LES pediátrico (LESp) representa el 15% de todos los pacientes con LES. La afectación renal y neuropsiquiátrica es más agresivo en el LESp, siendo la afectación de un solo órgano la forma clínica de aparición más común. Formas de presentación como infarto cerebral y serositis son manifestaciones poco frecuentes en el LESp. El tratamiento de un LESp no difiere al de las formas adultas y el arsenal terapéutico es el mismo. El rituximab (RTX) es un agente biológico utilizado a nivel mundial en LES con excelentes resultados, sin embargo, aún no existe consenso sobre su eficacia real en LESp. Objetivos . Presentación de 2 casos de LESp con infarto cerebral y serositis como forma de presentación, que no respondieron a la terapia convencional pero sí a RTX. Métodos . Reporte de caso, con descripción del cuadro clínico, método diagnóstico y forma de tratamiento. Resultados. Primer caso: mujer de 16 años que consulta por cefalea progresiva con crisis tónico-clónica. La tomografía cerebral mostró un infarto cerebral frontoparietal izquierdo. En el examen físico se encontró livedo reticularis en miembros inferiores, dolor articular, caída del cabello y úlceras orales. Las pruebas revelaron anemia normocítica, trombocitopenia, disminución del complemento, 1/320 ANA con patrón homogéneo, 3.200 mg de proteína en muestra de orina de 24 horas y anticuerpos antifosfolipídicos negativos. Se realizó diagnóstico de LESp con compromiso renal, neurológico y hematológico, decidiendo uso de metilprednisolona 1 g EV diario durante 3 días, para luego pasar a ciclofosfamida 1 g EV mensual por 6 meses. Después de 3 meses persisten proteinuria, fatiga y artralgias. Por este motivo, se decidió utilizar rituximab a una dosis de 375 mg / m2 en días 1 y 15 cada 6 meses. Tras 4 infusiones, la proteinuria desapareció, así como las artralgias y malestar general. Actualmente mantiene scores SLEDAI-2K en remisión, con dosis bajas de prednisona. Segundo caso: niño de 10 años, presentó dolor abdominal difuso con distensión asociada de inicio más o menos abrupto. Se agregó cansancio, dificultad para respirar y palpitaciones. Una radiografía simple de abdomen no mostró niveles hidroaéreos, pero la placa torácica demostró derrame pleural bilateral con agrandamiento de la silueta cardíaca. Un ecocardiograma y una ecografía abdominal reveló derrame pericárdico y ascitis respectivamente. Al examen físico se observó palidez general, edema translúcido de miembros inferiores, roce pericárdico y disminución del soplo vesicular en ambas bases pulmonares. Las pruebas de laboratorio mostraron leucopenia, linfopenia, anemia normocítica, reactantes de fase aguda elevados, ANA 1/560, anti-ADN 280 U / mL, complemento disminuido, transaminasas elevadas, urea y creatinina normales. Se diagnosticó LESp y se pulsó con metilprednisolona 30 mg / kg / dosis durante 4 días, para luego pasar a micofenolato 600 mg / m2 diarios. Inicialmente hubo mejoría, pero después de 2 meses reapareció la serositis inicial. Se decidió usar rituximab 375 mg / m2. Después de la segunda infusión la serositis desapareció, normalizándose valores de hemograma, complemento y transaminasas. Actualmente se encuentra en remisión, con dosis bajas de prednisona. Conclusión . Los casos presentados debutaron con infarto cerebral y serositis, mostraron ANA elevados títulos y disminución del complemento. Ambos casos mejoraron con rituximab tras el fracaso a ciclofosfamida y micofenolato. Se obtuvo el consentimiento informado de los padres y los pacientes.

---

Introduction . Pediatric systemic lupus erythematosus (pSLE) represents 15% of all SLE patients. Renal and neuropsychiatric involvement are more aggressive in pSLE, and single organ involvement is the most commonly found clinical form. Conditions such as cerebral infarction and serositis are unusual manifestation of pSLE. Therapy for pSLE is not different from that for the adult forms, and the therapy armamentarium is the same. Rituximab (RTX) is a worldwide used biological for SLE, with excellent results; however, there is still no consensus with respect to is real efficacy in pSLE. Objectives . Presentation of two pSLE cases with cerebral infarction and serositis as main characteristics, who did not respond to conventional therapy, but who did respond to RTX. Methods . Case report, describing the clinical presentation, diagnostic methods, and therapy approach used. Results . First case: This is a sixteen-year-old girl who was brought because of progressing headache and a tonic-clonic crisis. The brain CT scan showed a left frontoparietal cerebral infarction. Physical examination revealed livedo reticularis in both legs, joint pain, hair loss, and mouth ulcers. Laboratory tests revealed normocytic anemia, thrombocytopenia, reduced complement, 1/320 ANA with a homogeneous pattern, 3.200 mg 24-hour proteinuria, and negative anti-phospholipidic antibodies. A pSLE diagnosis was made, with renal, neurologic, and hematologic involvement, so it was decided to use methylprednisolone, 1 gram IV per day for three days, and then switch to cyclophosphamide 1 g IV per month for 6 months. After three months, proteinuria, fatigue, and arthralgia persisted. For this reason, it was decided to administer rituximab, 375 mg/m2 in days 1 and 15, every six months. After four infusions, proteinuria, joint pain and malaise all disappeared. Nowadays this patient maintains SLEDAI-K scores in remission, and she is also receiving low-dose prednisone. Second case: This is a ten-year-old boy, who presented with abrupt diffuse abdominal pain associated with (abdominal) distention. Other manifestations were tiredness, shortness of breath, and palpitations. A plain abdomen X-ray film did not show hydro-aerial levels, but the chest X-ray film showed bilateral pleural effusion, and enlarged cardiac silhouette. Cardiac ultrasonography and abdominal ultrasonography revealed pericardial effusion and ascites, respectively. Findings in physical examination showed pallor translucid edema of the legs, pericardial throbbing, and reduced respiratory sounds in both pulmonary bases. Laboratory tests revealed leukopenia, lymphopenia, normocytic anemia, elevated acute phase reactants, ANA 1/560, anti-DNA 280 U/mL, reduced complement, elevated transaminases, and normal urea and creatinine. pSLE was diagnosed, and therapy instituted was methylprednisolone 30 mg/Kg/dose for 4 days, then it was switched to mycophenolate 600 mg/m2 per day. There was improvement initially, but after two months, serositis reappeared. Then it was decided to start rituximab 375 mg/m2. After the second infusion, serositis disappeared, and CBC, complement, and transaminase values returned to normal. Nowadays the patient is in remission, and he is receiving low-dose prednisone. Conclusión . Both presented cases featured cerebral infarction and serositis. They also showed high ANA titers and reduced complement. Both patients improved their condition with rituximab after failure with cyclophosphamide and mycophenolate. Informed consent from both parents and patients was obtained.