Efficacy and safety of rituximab in children and adolescents with mature B-cell non-Hodgkin's lymphoma: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis.@*METHODS@#The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis.@*RESULTS@#The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24).@*CONCLUSIONS@#The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.

Rituximab use in adult glomerulopathies and its rationale / Uso do rituximabe em glomerulopatias em adultos e justificativas

Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.

Resumo As glomerulopatias figuram entre as principais causas de doença renal terminal. Nos últimos anos, a pesquisa clínica efetuou contribuições significativas para a compreensão desse grupo de patologias. Recentemente, o rituximabe (RTX) surgiu como um tratamento razoavelmente seguro. As diretrizes do Kidney Disease: Improving Global Outcomes (KDIGO) recomendam o RTX apenas como tratamento inicial na vasculite associada ao ANCA (VAA) e em pacientes não respondedores com nefrite lúpica (NL), embora não sejam atualizadas desde 2012. Atualmente, o RTX parece ser pelo menos tão eficaz quanto outros esquemas imunossupressores na nefropatia membranosa idiopática (NMI). Na doença por lesão mínima (DLM), o medicamento pode proporcionar um período de remissão duradouro em pacientes córtico-dependentes ou com recidivas frequentes. Resultados preliminares corroboram o uso de RTX em pacientes com NL membranosa pura e glomerulonefrite membranoproliferativa (GNMP) mediada por imunoglobulina, mas não em pacientes com NL classe III/IV ou GNMP mediada por complemento. Os achados a respeito de glomeruloesclerose segmentar e focal (GESF) idiopática e doença por anticorpo antimembrana basal glomerular (anti-MBG) não são conclusivos em função do pequeno número, porte e heterogeneidade dos estudos publicados até o presente momento. Por fim, a imunossupressão com RTX não é particularmente útil na nefropatia por IgA. A presente revisão apresenta o racional da prescrição de RTX nas diferentes glomerulopatias, desfechos e segurança. Nesse sentido, foram incluídos ensaios clínicos randomizados (ECRs) realizados em adultos, sempre que possível. Pesquisas bibliográficas foram realizadas nas bases de dados do clinictrials.gov e no PubMed.

Pioderma gangrenoso vulvar: revisión de la literatura a propósito de un caso causado por rituximab / Vulvar pyoderma gangrenosum: review of the literature on a case caused by rituximab

RESUMEN El Pioderma Gangrenoso (PG) es una enfermedad inflamatoria necrotizante crónica, que pertenece al espectro de las dermatosis neutrofílicas. Histológicamente se caracteriza por mostrar un infiltrado inflamatorio denso de neutrófilos de origen no infeccioso. El PG suele asociarse a enfermedades sistémicas como la enfermedad inflamatoria intestinal, la artritis reumatoide o diversas enfermedades hematológicas. Presenta fenómeno de patergia y suele responder satisfactoriamente a tratamientos inmunosupresores. Su etiología no está bien definida. En la literatura se han publicado 15 casos de pioderma gangrenoso vulvar asociado al uso de rituximab. Nosotros presentamos un nuevo caso, que tuvo lugar en una mujer de 37 años en tratamiento de mantenimiento con rituximab por un linfoma no Hodgkin folicular. El rituximab (MabThera®) es un anticuerpo que reconoce la molécula CD20, que es una proteína no glucosilada que se expresa en la superficie de los linfocitos B. Este fármaco se ha utilizado para el tratamiento de diferentes enfermedades reumatológicas en los últimos años.

ABSTRACT Pyoderma Gangrenosum is a chronic necrotizing inflammatory disease that belongs to the spectrum of Neutrophilic Dermatoses. Histologically, it is characterized by a dense inflammatory infiltrate of non-infectious neutrophils. Etiology is not yet well defined. It is usually associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis or hematological diseases. It presents pathergy phenomenon and usually respond satisfactorily to immunosuppressive treatments. There have been published only 15 cases of vulvar pyoderma gangrenosum associated with the use of rituximab. We present a new case, which occurred in a 37-year-old woman on maintenance treatment with rituximab for a follicular non-Hodgkin's lymphoma. Rituximab (MabThera®) is an antibody that recognizes the CD20 molecule, which is a non-glycosylated protein that is expressed on the surface of B lymphocytes. This drug has been used for the treatment of different rheumatic diseases in recent years.

Predictores del uso off-label de rituximab en pacientes adultos: un estudio piloto / Off-label use of rituximab and associated factors in adult patients: a pilot study abstract

Introducción: comprender los factores que condicionan el uso off-label de los agentes monoclonales es crucial para su utilización racional. El objetivo de nuestro estudio fue describir la prevalencia de uso off-label de rituximab y los factores médicos, clínicos y socioeconómicos que se vinculan con dicha práctica. Métodos: estudio de corte transversal retrospectivo. Incluimos pacientes adultos con una primera indicación de rituximab entre 2010 y 2016. La exposición primaria fue definida como el momento de la pérdida de patente de rituximab. Otros factores considerados fueron el diagnóstico de base y las comorbilidades, así como también datos referentes a los médicos tratantes. El evento primario fue la prevalencia de prescripción off-label de rituximab. Utilizamos un modelo de regresión logística para estimar la asociación entre el tiempo y el evento primario. Resultados: de 160 pacientes adultos que iniciaron tratamiento con rituximab y fueron potencialmente elegibles se tomó una muestra aleatoria; 22 de ellos fueron incluidos en el análisis final. La prevalencia de uso off-label fue del 30,4% (IC 95%, 13,9 a 54,9%). No evidenciamos un cambio en el patrón de prescripción de rituximab asociado al tiempo de caída de la patente. El único factor predictor de dicho uso fueron las internaciones previas (7 vs. 1, p = 0,04). Conclusión: el uso off-label de rituximab es frecuente en nuestra población. Futuros estudios deberían estar dirigidos a determinar los factores asociados a esta práctica, así como a estimar el impacto en términos de eficacia y potencial toxicidad en esta población. (AU)

Background: the description of those characteristics that are associated with the off-label use of monoclonal antibodies remains paramount if we are to maximize the rational use of available resources. Our main objective was to describe the prevalence of off-label use of Rituximab, in addition to its associated factors (for example, prescribing physician and patient´s clinical and socioeconomic characteristics). Methods: we designed a retrospective cross-sectional study which included patients starting treatment with Rituximab between 2010 and 2016. Our main exposure was the time when Rituximab´s patent expired. Other potential factors associated with the off-label prescription pattern were baseline diagnosis and comorbidities in addition to the main characteristics of the prescribing physician. The main outcome was the prevalence of off-label use of Rituximab. We used a multivariate logistic regression model in order to estimate the association between time and our main endpoint. Results: out of 160 eligible patients that started treatment with Rituximab we included 22 adult patients in our main analysis by conducting a random sampling procedure. The prevalence of off-label use was 30.4% (95% CI, 13.9 to 54.9%). We did not find a change in the prescription pattern of Rituximab with regards to time and patent expiration. The only factor associated with off-label use were previous hospitalizations (7 vs. 1, p = 0.04). Conclusions: the off-label use of Rituximab is common in our population. Future studies evaluating distinct factors associated with such use as well as its impact in both potential efficacy and toxicity are warranted. (AU)

Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

ABSTRACT HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

Farmacoepidemiología del rituximab en un hospital pediátrico de alta complejidad / Rituximab pharmacoepidemiology in a tertiary-care pediatric hospital

Objetivo: Estudiar el perfil farmacoepidemiológico de rituximab en un hospital pediátrico de alta complejidad. Métodos: Diseño: Estudio de utilización de medicamentos: Prescripción ­ Indicación. Lugar: Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina. Participantes: pacientes que recibieron rituximab, de enero 2012 a junio 2014, comprendió 58 pacientes con 17 patologías distintas. Mediciones principales: se analizó la efectividad como: positiva, negativa e incierta. Se estudiaron las reacciones adversas al medicamento, que fueron procesadas y notificadas. Se evaluó también la manera de premedicar la administración del fármaco. Resultados: treinta y dos pacientes (55%) presentaron un resultado positivo luego del tratamiento,16 pacientes (29%) presentaron un resultado negativo y 9 (16%) tuvieron un resultado incierto. Los mejores resultados se obtuvieron en el tratamiento de pacientes con trasplante de médula ósea con infección por virus de Epstein Barr y en linfoma de Burkitt. Se hallaron 41 reacciones adversas en a 22 pacientes, la mayoría estuvieron relacionadas a la infusión. Se premedicó de 8 formas distintas a los pacientes. Conclusiones: Las patologías con mejores resultados son similares a lo esperado según la literatura consultada. El perfil de seguridad del rituximab lo ubica como un medicamento riesgoso. Es necesario mejorar el registro para ejecutar programas de farmacoepidemiología (AU)

Aim: To study the pharmacoepidemiological profile of rituximab in a pediatric tertiary-care hospital. Methods: Study design: Evaluation of medication use: Prescription ­ Indication. Place: Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina. Participants: patients receiving rituximab between January 2012 and June 2014, including 58 patients with 15 different conditions. Main measurements: effectivity was defined as: positive, negative, and uncertain. Adverse events associated with rituximab were studied, processed, and notified. Premedication for administration of the drug was also studied. Results: Thirty-two patients (55%) had a positive response,16 patients (29%) had a negative response , and 9 (16%) had an uncertain response to the treatment. The best results were obtained in patients undergoing bone marrow transplantation with Epstein Barr virus and in those with Burkitt's lymphoma. Forty-one adverse events were observed in 22 patients, related to drug-infusion in the majority of cases. Pre-medication was administered in the patients in 8 different ways. Conclusions: The conditions in which the best results were achieved were similar to those reported in the literature. The safety profile of rituximab places it among risk drugs. Registration needs to be improved to run pharmacoepidemiology programs (AU)

Tormenta de citoquinas: reacción adversa inhabitual por rituximab. caso clínico / Shock as an adverse reaction to rituximab: case report

Rituximab is a plausible alternative first-line treatment of ANCA-associated vasculitis. Adverse effects related to its infusion are common and usually have a benign course. However, there have been reports of refractory cardiogenic shock simulating septic shock. We report an 81-year-old male with the diagnosis of ANCA associated vasculitis. Rituximab 500 mg was administered intravenously for a relapse. The infusion proceeded without incident. However, 24 hours after its administration the patient began with fever, chills, coughing and strong malaise. The patient was transferred to the critical patient unit where a septic shock was suspected and resuscitative measures were started. However, the fast response to moderate doses of vasoactive drugs and complementary tests did not support an infectious etiology for the shock. Antimicrobials were discontinued and systemic corticosteroids were maintained, achieving remission of the symptoms. Shock as an unusual adverse reaction to Rituximab was suspected.

Eficacia y seguridad de cladribina en el tratamiento de pacientes con diagnóstico de tricoleucemia / Efficacy and safety of cladribine in the treatment of patients diagnosed with tricholeukemia

INTRODUCCIÓN: Antecedentes: En el present dictamen preliminar expone la evaluación de tecnología de la eficacia y seguridad del uso de cladribina en el tratamiento de pacientes adultos con diagnostico de leucemia de células vellosas o tricoleucemia. Así, los médicos hematólogos. Aspectos Generaels: La leucemia de células vellosas o tricoleucemia es una neoplasia de los linfocitos B pequeños que se caracteriza por la presencia de "células peludas" o células con núcleos ovales indentados y citoplasma abundante con proyecciones citoplasmáticas "pelulas", obervables en el 90% de los pacientes que se padecen. Los marcadores más comunes expresados por las células peludas son el CD19, CD20 y CD22, con una notable co-expressión de CD103, CD25, CD11c. Tecnologia Sanitaria de Interés: Cladribina es un agente antineoplásico sintético que se encuentra disponbile en viales para infusión endovenosa continua. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de cladribina en el tratamiento de pacientes con tricoleucemia en las bases de datos de Medline, Embase, Scopus, Web of Science, Cinahl, Cochrane y Tripdatabase. RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de la evidencia que sustente el uso de cladribina en el tratamiento de la tricoleucemia según la pregunta PICO establecida. CONCLUSIONES: Rituximab ha sido empleado en EsSalud como primera linea de tratamiento frente a la falta de acceso a cladribina. Sin embargo, ciertos pacientes presentan respuesta inadecuada o intolerancia a rituximab y requieren otras alternativas de tratamiento. Adicionalmente, se ha solicitado el uso de cladribina como terapia de primera línea en pacientes con tricoleucemia dado que en la actualidad se emplea un medicamento que no se encuentra indicado como primera líena para lla condición. En base a esta solicitud se llevó a cabo una rewvisión de la literatura sobre la eficacia y seguridad de cladribina en la poblaciones de pacientes previamente tratados y no-tratados. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI aprueba el uso de cladribina como alternativa de tratamiento en pacientes con tricoleucemia previamente tratados o como primera línea de tratamiento. El perído de vigencia del presente dictamen preliminar es de dos años y la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a nueva evidencia que pueda surgir en el tiempo.

Azathioprine-induced accelerated cutaneous and pulmonary nodulosis in a patient with rheumatoid arthritis

We report the case of a 42-year-old female with a 5-year history of rheumatoid arthritis treated with Rituximab and Azathioprine. Three months after the initiation of Azathioprine, the patient started with dry cough and noted the rapid development of multiple subcutaneous nodules on her right leg. CT scan of the chest demonstrates pulmonary nodulosis. Skin biopsy was compatible with rheumatoid nodule. A diagnosis of "accelerated cutaneous and pulmonary nodulosis" was considered. Azathioprine was discontinued and Rituximab was restarted. Two months later, most of the subcutaneous nodules had disappeared. This is the second case report of accelerated rheumatoid nodulosis in association with Azathioprine treatment.