RESUMEN
BACKGROUND: Rituximab is associated with high infection rates, but studies of infections following rituximab in youth with childhood-onset SLE (cSLE) are limited. We conducted a retrospective longitudinal cohort study to assess the incidence of hospitalised infections following rituximab among children with cSLE and to assess changes in hospital-based rituximab administration over time. METHODS: Youth ages 2-21 years with an International Classification of Diseases (ICD) code for SLE who received rituximab during admission to a Pediatric Health Information System hospital from 2009 to 2021 were included. Incidence rates for infections requiring hospitalisation over the 12 months following first rituximab administration were calculated. Rituximab use by year of hospital discharge was tabulated. RESULTS: We identified 1567 children with cSLE who received rituximab. 219 children were admitted with an infection within 1 year after first rituximab administration, for an incidence rate of 140 cases per 1000 patient-years. Seven children (0.44%) died during a hospitalisation with an infection in the year following rituximab administration. The most common hospitalised infections were bacterial pneumonia, sepsis and cellulitis. 12 children were hospitalised with COVID-19, none of whom died. Hospitalisations with rituximab administered decreased from 2019 to 2021. CONCLUSIONS: In this cohort of patients with cSLE who received inpatient treatment with rituximab, we observed a 14% rate of hospitalisation with infection in the year following rituximab administration among youth with cSLE. Rituximab use declined during the COVID-19 pandemic. No fatalities with COVID-19 were observed. Given the lack of outpatient data, including doses of concomitant medications and disease activity measures, further research is needed to identify risk factors for infection following rituximab among children with cSLE.
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Hospitalización , Lupus Eritematoso Sistémico , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Adolescente , Niño , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Femenino , Estudios Retrospectivos , Masculino , Preescolar , Hospitalización/estadística & datos numéricos , Estudios Longitudinales , Incidencia , Adulto Joven , COVID-19/epidemiología , SARS-CoV-2RESUMEN
BACKGROUND: In recent years a broader range of immunomodulatory and immunosuppressive treatment options have emerged for people with progressive forms of multiple sclerosis (PMS). While consensus supports these options as reducing relapses, their relative benefit and safety profiles remain unclear due to a lack of direct comparison trials. OBJECTIVES: To compare through network meta-analysis the efficacy and safety of alemtuzumab, azathioprine, cladribine, cyclophosphamide, daclizumab, dimethylfumarate, diroximel fumarate, fingolimod, fludarabine, glatiramer acetate, immunoglobulins, interferon beta 1-a and beta 1-b, interferon beta-1b (Betaferon), interferon beta-1a (Avonex, Rebif), laquinimod, leflunomide, methotrexate, minocycline, mitoxantrone, mycophenolate mofetil, natalizumab, ocrelizumab, ofatumumab, ozanimod, pegylated interferon beta-1a, ponesimod, rituximab, siponimod, corticosteroids, and teriflunomide for PMS. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase up to August 2022, as well as ClinicalTrials.gov and the WHO ICTRP. SELECTION CRITERIA: Randomised controlled trials (RCTs) that studied one or more treatments as monotherapy, compared to placebo or to another active agent, for use in adults with PMS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We performed data synthesis by pair-wise and network meta-analysis. We assessed the certainty of the body of evidence according to GRADE. MAIN RESULTS: We included 23 studies involving a total of 10,167 participants. The most frequent (39% of studies) reason for a rating of high risk of bias was sponsor role in study authorship and data management and analysis. Other concerns were performance, attrition, and selective reporting bias, with 8.7% of studies at high risk of bias for all three of these domains. The common comparator for network analysis was placebo. Relapses over 12 months: assessed in one study (318 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Relapses over 24 months: assessed in six studies (1622 participants). The number of people with clinical relapses is probably trivially reduced with rituximab (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.19 to 1.95; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. Relapses over 36 months: assessed in four studies (2095 participants). The number of people with clinical relapses is probably trivially reduced with interferon beta-1b (RR 0.82, 95% CI 0.73 to 0.93; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. Disability worsening over 24 months: assessed in 11 studies (5284 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Disability worsening over 36 months: assessed in five studies (2827 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Serious adverse events: assessed in 15 studies (8019 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Discontinuation due to adverse events: assessed in 21 studies (9981 participants). The number of people who discontinued treatment due to adverse events is trivially increased with interferon beta-1a (odds ratio (OR) 2.93, 95% CI 1.64 to 5.26; high certainty evidence). The number of people who discontinued treatment due to adverse events is probably trivially increased with rituximab (OR 4.00, 95% CI 0.84 to 19.12; moderate certainty evidence); interferon beta-1b (OR 2.98, 95% CI 1.92 to 4.61; moderate certainty evidence); immunoglobulins (OR 1.95, 95% CI 0.99 to 3.84; moderate certainty evidence); glatiramer acetate (OR 3.98, 95% CI 1.48 to 10.72; moderate certainty evidence); natalizumab (OR 1.02, 95% CI 0.55 to 1.90; moderate certainty evidence); siponimod (OR 1.53, 95% CI 0.98 to 2.38; moderate certainty evidence); fingolimod (OR 2.29, 95% CI 1.46 to 3.60; moderate certainty evidence), and ocrelizumab (OR 1.24, 95% CI 0.54 to 2.86; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. AUTHORS' CONCLUSIONS: The number of people with PMS with relapses is probably slightly reduced with rituximab at two years, and interferon beta-1b at three years, compared to placebo. Both drugs are also probably associated with a slightly higher proportion of withdrawals due to adverse events, as are immunoglobulins, glatiramer acetate, natalizumab, fingolimod, siponimod, and ocrelizumab; we have high confidence that this is the case with interferon beta-1a. We found only low or very low certainty evidence relating to disability progression for the included disease-modifying treatments compared to placebo, largely due to imprecision. We are also uncertain about the effect of interventions on serious adverse events, also because of imprecision. These findings are due in part to the short follow-up of the included RCTs, which lacked detection of less common severe adverse events. Moreover, the funding source of many included studies may have introduced bias into the results. Future research on PMS should include head-to-head rather than placebo-controlled trials, with a longer follow-up of at least three years. Given the relative rarity of PMS, controlled, non-randomised studies on large samples may usefully integrate data from pivotal RCTs. Outcomes valuable and meaningful to people with PMS should be consistently adopted and measured to permit the evaluation of relative effectiveness among treatments.
Asunto(s)
Inmunosupresores , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Agentes Inmunomoduladores/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/efectos adversos , Rituximab/uso terapéutico , Rituximab/efectos adversos , RecurrenciaRESUMEN
Rituximab occasionally induces reactivation of hepatitis C virus (HCV) in patients with resolved HCV infection, sometimes with fatal consequences. As rituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) and is more widely used, there is a lack of studies reporting the effectiveness and safety of rituximab in patients with PLA2R-associated MN and resolved HCV infection. A single-center retrospective study was conducted on PLA2R-associated membranous nephropathy (MN) patients who were HCVAb positive but HCV-RNA negative and treated with rituximab. A total of 598 adult patients with PLA2R-associated MN who underwent rituximab therapy were screened. General clinical information, including gender, age, pathological data, and previous treatment plans, was collected from medical records. Routine blood tests, liver and kidney function assessments, blood lipid profiles, 24-h urine protein levels, anti-PLA2R antibody titers, circulating B-cell counts, and HCV viral loads were measured at the time of rituximab infusion and repeated at intervals of 1-3 months post-rituximab administration. A total of 8 patients were enrolled, with a median follow-up period of 19.00 (range: 16.00-25.25) months. Among the 8 patients, 5 were male, and the mean age was 50.13 ± 4.29 years. Histological findings indicated that tubuloreticular inclusions, mesangial deposits, intramembranous deposits, and subendothelial deposits were not observed in any of the 8 patients. The overall 1-year remission rate for these patients was 75%, accompanied by a significant reduction in proteinuria. Additionally, blood albumin levels increased significantly, and renal function remained stable. No increase in HCV viral load and stable liver function tests were observed throughout the entire follow-up period. This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and resolved HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials.
Asunto(s)
Glomerulonefritis Membranosa , Hepacivirus , Hepatitis C , Receptores de Fosfolipasa A2 , Rituximab , Humanos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/patología , Receptores de Fosfolipasa A2/inmunología , Masculino , Femenino , Persona de Mediana Edad , Hepatitis C/tratamiento farmacológico , Estudios Retrospectivos , Adulto , Hepacivirus/efectos de los fármacos , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. METHODS: We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. RESULTS: The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p < 0.001), and developed severe COVID-19 (33.3% vs. 4.7%, p < 0.001) were higher in patients with obinutuzumab than in those with rituximab. Multivariate analyses showed that obinuzumab treatment was associated with higher incidences of prolonged SARS-CoV-2 infection (OR 27.05, 95% CI 3.75-195.22, p = 0.001) and severe COVID-19(OR 15.07, 95% CI 2.58-91.72, p = 0.003). CONCLUSIONS: Our study suggested that patients treated with obinutuzumab had a higher risk of prolonged SARS-CoV-2 infection and severe COVID-19 than those treated with rituximab.
Asunto(s)
Anticuerpos Monoclonales Humanizados , COVID-19 , Rituximab , SARS-CoV-2 , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , SARS-CoV-2/efectos de los fármacos , Tratamiento Farmacológico de COVID-19 , Resultado del Tratamiento , Adulto , Linfoma de Células B/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported. CASE PRESENTATION: A 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI. CONCLUSION: IVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected.
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COVID-19 , Huésped Inmunocomprometido , Inmunoglobulinas Intravenosas , Rituximab , SARS-CoV-2 , Lesión Pulmonar Aguda Postransfusional , Humanos , Masculino , Persona de Mediana Edad , COVID-19/complicaciones , Rituximab/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/efectos adversos , Lesión Pulmonar Aguda Postransfusional/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , BetacoronavirusRESUMEN
Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 µg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.
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Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Masculino , Femenino , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Persona de Mediana Edad , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Rituximab/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Anciano , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Prednisona/efectos adversos , Vincristina/uso terapéutico , Vincristina/efectos adversos , Vincristina/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano de 80 o más Años , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of a low-dose, long-term rituximab regimen in the treatment of idiopathic CIDP. METHODS: This study included 15 CIDP patients treated with rituximab. Patients were administered 600 mg of rituximab intravenously every 6 months. Baseline evaluation was conducted before the initiation of rituximab treatment and subsequent evaluations were conducted 6 months after each rituximab infusion at on-site visits. Clinical improvement was objectively determined by improvement of scale score at least decrease ≥1 INCAT or mRS or increase ≥4 MRC or ≥8 cI-RODS after each infusion compared to baseline evaluation. RESULTS: Fifteen CIDP patients were included and 10 of them were typical CIDP and five were distal CIDP. Nine in 15 (60%) patients after first infusion and three in six (50%) patients after second infusion exhibited significant clinical improvement compared to baseline evaluation. Additionally, rituximab facilitated a reduction or cessation of other medications in 73% of patients at last visit. The safety profile was favorable, with no reported adverse events. CONCLUSION: Rituximab presents a promising therapeutic option for idiopathic CIDP, offering both efficacy and safety with a low-dose, long-term regimen.
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Factores Inmunológicos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Rituximab , Humanos , Rituximab/administración & dosificación , Rituximab/efectos adversos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND Fermenting bacilli producing lactic acid, including Bifidobacterium spp., are supposed to have low pathogenicity and no virulence for humans. Probiotics consisting of those fermenting bacilli can prevent and treat symptomatic gastrointestinal conditions, such as diarrhea. We use probiotics even in cancer patients, those who are immunocompromised, because a preferable effect to the intestinal commensal microbiome has been shown in a recent report. Some case reports warn of a rare risk of bloodstream infection caused by probiotics. However, complete prohibition of probiotic use in cancer patients abandons the benefits. CASE REPORT A 75-year-old Japanese woman with malignant lymphoma was treated with immune-chemotherapy regimen consisting of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient had onset of febrile neutropenia during chemotherapy and had Bifidobacterium breve bloodstream infection on day 8 after the eighth R-CHOP treatment. She had usually eaten commercial yogurt every morning. This yogurt was produced from only Lactobacillus bulgaricus and Streptococcus thermophilus. It did not contain Bifidobacterium breve. The bloodstream infection in this case looked like it derived from her food; however, it was not associated with her habitual foods. The patient was treated with meropenem for 8 days and experienced complete remission of the bloodstream infection. CONCLUSIONS We speculate that fermenting bacilli can also be a source of bloodstream infection, not necessarily associated with probiotic strains, in cancer patients treated with chemotherapy. Additionally, we recommend that probiotics can alleviate alimentary tract symptoms in immunocompromised patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Probióticos , Humanos , Femenino , Anciano , Probióticos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Doxorrubicina/efectos adversos , Vincristina/uso terapéutico , Infecciones por Bifidobacteriales/microbiología , Rituximab/uso terapéutico , Rituximab/efectos adversos , Prednisona/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bifidobacterium breve , Linfoma/tratamiento farmacológicoRESUMEN
Cystoid macular edema (CME) is considered a rare adverse effect of rituximab use, with only a limited number of cases published in the literature. Although its etiopathogenesis is still unknown, its mechanism seems to be related to a transient elevation of cytokines after rituximab infusion resulting in an increased permeability of retinal vessels. We report the first case of rituximab-induced CME in a patient with systemic lupus erythematosus (SLE), where rituximab was used to treat hematological complications. A month after the 2nd infusion, the patient developed blurred vision and decreased visual acuity in the right eye. An optic coherence tomography (OCT) was performed, being diagnosed with CME. Rituximab was then discontinued, exhibiting a complete resolution of the condition within 4 weeks. The aim of our work is to report the first case in a patient with SLE and also carry out a brief review of the subject comparing it to all previously published cases.
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Lupus Eritematoso Sistémico , Edema Macular , Rituximab , Humanos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Edema Macular/inducido químicamente , Edema Macular/etiología , Edema Macular/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Femenino , Tomografía de Coherencia Óptica , AdultoRESUMEN
Objective To assess the efficacy and safety of three treatment modalities (rituximab targeted B-cell therapy, calcium-phosphate inhibitor in conjunction with low-dose corticosteroids, and full-dose corticosteroids combined with cyclophosphamide) for patients at intermediate or high risk of idiopathic membranous nephropathy (IMN) and to analyze the factors impacting the remission rates of IMN. Methods A retrospective cohort study was conducted to analyze patients diagnosed with IMN in our nephrology department via renal biopsy, identifying a total of 148 patients at intermediate or high risk. These patients were categorized into three treatment groups: a RTX group with 60 patients receiving rituximab, a CNI group with 42 patients receiving calcineurin inhibitors, and a CTX group with 46 patients received cyclophosphamide. Baseline measurements of 24-hour urine protein, serum albumin, blood creatinine, uric acid, estimated glomerular filtration rate (eGFR), and serum anti-phospholipase A2 receptor antibody levels were recorded at the onset of the follow-up. Subsequently, changes in 24-hour urine protein, eGFR, remission rates, and occurrence of adverse events among the three patient groups were compared at 6, 12, and 18 months post-treatment. Moreover, COX regression analysis was employed to ascertain factors influencing the remission rate of IMN. Results At the outset of the follow-up period, no significant difference existed in baseline characteristics such as gender, age, 24-hour urine protein quantification, serum albumin, serum creatinine, uric acid, eGFR, serum anti-PLA2R antibody levels, body mass index (BMI), and systolic blood pressure among the patients, indicating the comparability of three groups. After 6 months, there were no notable changes in 24-hour urine protein quantification and eGFR among the three groups; however, remission rates in the RTX and CTX groups were lower than those in the CNI group. By the 12-month mark, 24-hour urine protein quantification in the RTX group significantly decreased compared to the CTX group, with overall remission rates showing no significant differences among the three groups. By the 18-month milestone, 24-hour urine protein quantification in the RTX group remained notably lower than that in the CTX group, with significantly higher eGFR levels. Additionally, the CTX group exhibited lower 24-hour urine protein quantification compared to the CNI group, with both RTX and CTX groups displaying higher remission rates than the CNI group. Predominant adverse reactions in the RTX group included infusion reactions and infections, whereas the CNI group were associated with metabolic syndrome and elevated serum creatinine, and the CTX group primarily experienced hepatic dysfunction. Multifactorial COX regression analysis revealed an association between baseline anti-PLA2R antibodies and remission rates of IMN (HR=1.162, 95% CI 1.078-1.249). Conclusion RTX therapy for IMN exhibits a gradual onset of action, boasting a superior disease remission rate at 18 months in comparison to CNI. It demonstrates a similarity to CTX in this aspect and offers prolonged maintenance of remission. Conversely, CNI demonstrates a rapid onset of action but poses a risk of exacerbating renal impairment in patients. Notably, elevated levels of serum anti-PLA2R antibodies emerge as an independent risk factor influencing remission in IMN.
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Glomerulonefritis Membranosa , Inmunosupresores , Rituximab , Humanos , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/orina , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Tasa de Filtración Glomerular/efectos de los fármacos , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Receptores de Fosfolipasa A2/inmunologíaRESUMEN
Rituximab has been used to treat MS patients in Iceland for over a decade. However, long-term effect of rituximab on leukocyte populations has not yet been elucidated. By retrospective analysis of flow cytometric data from 349 patients visiting the neurological ward at The National University Hospital of Iceland from 2012 to 2023 for rituximab treatment, the long-term effect of rituximab and whether the effect was dose dependent (1000mg vs 500mg) was evaluated. No difference was detected in efficacy of B cell depletion in patients treated with 500mg as an initial dose of rituximab when compared to 1000mg. Long-term use of rituximab led to an increase in T cell count (p=0,0015) in patients receiving 3-8 doses of rituximab (1.5-8 years of treatment). The increase occurred in both CD4+ (p=0,0028) and CD8+ T cells (p=0,0015) and led to a decrease in the CD4/CD8 ratio (p=0,004). The most notable difference lies in reshaping the balance between näive and effector CD8+ T cells. The clinical implications of long-term treatment with rituximab and its effect on the T cell pool needs to be explored further. Since no difference in B cell depletion was detected between the two patient groups, 1000mg as an initial dose might be excessive, suggesting a personalized dosing regimen might have therapeutic and financial advantages.
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Esclerosis Múltiple , Rituximab , Humanos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Rituximab/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Estudios Retrospectivos , Recuento de Linfocitos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Anciano , Relación CD4-CD8 , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacosRESUMEN
OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.
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Agammaglobulinemia , Enfermedades Autoinmunes , Infecciones , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Femenino , Masculino , Agammaglobulinemia/epidemiología , Persona de Mediana Edad , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Estudios Retrospectivos , Adulto , Infecciones/etiología , Infecciones/epidemiología , Anciano , Glucocorticoides/uso terapéutico , Factores de Riesgo , China/epidemiología , Inmunoglobulina G/sangreRESUMEN
INTRODUCTION: Patients with resolved hepatitis B virus infection undergoing rituximab are at risk of hepatitis B virus reactivation without antiviral prophylaxis. However, the risk in such patients treated with rituximab-based regimens for membranous nephropathy is not clear. We evaluated the risk of hepatitis B virus reactivation in membranous nephropathy patients with resolved infection undergoing rituximab-based regimens without antiviral prophylaxis. METHODS: Clinical data of 51 membranous nephropathy patients with resolved hepatitis B virus infection undergoing rituximab-based regimens without antiviral prophylaxis were retrospectively analyzed. Among these, 21 patients were followed for more than 1 year after rituximab discontinuation. The clinical data collected aimed to assess patients' responses and the risk of hepatitis B virus reactivation during and after rituximab treatment. RESULTS: 30/51 (58.8 %) patients reached complete or partial remission at 12 months. None of the patients experienced HBsAg seroreversion during rituximab treatment. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and total bilirubin levels, as well as the numbers of patients who exceeded the upper limits of normal for alkaline phosphatase and prothrombin time, did not show any statistically significant difference during rituximab-based therapy. Neither did the anti-HBs level, the number of patients with protective anti-HBs titers exceeding 10 U/L, nor the levels of CD19+ B cells, CD4+ T cells, CD8+ T cells, and natural killer cells. Among the 21 patients followed for 12 (ranging from 12 to 19) months after rituximab discontinuation, no hepatitis B virus reactivation was observed. The mean anti-HBs level and the number of patients with anti-HBs titers over 10 U/L did not show any statistically significant difference during the extended follow-up of 33 patient-years. Neither did the CD4+ T cell, CD8+ T cell, nor the natural killer cell counts. One patient presented with an ALT level that exceeded the baseline value by three times and reached above 100 U/L, accompanied by elevations in AST, GGT, and ALP levels. Meanwhile, the anti-HBs titer was 816.09 U/L, and HBsAg was negative. CONCLUSION: The administration of rituximab-based regimens in membranous nephropathy patients with hepatitis B virus resolved infection leads to a low risk of hepatitis B virus reactivation without antiviral prophylaxis. Patient's immune status, drug combination, rituximab strategy should be fully evaluated when considering antiviral prophylaxis therapy.
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Glomerulonefritis Membranosa , Virus de la Hepatitis B , Hepatitis B , Rituximab , Activación Viral , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Masculino , Femenino , Hepatitis B/inmunología , Hepatitis B/tratamiento farmacológico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/virología , Activación Viral/efectos de los fármacos , Persona de Mediana Edad , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Estudios Retrospectivos , Adulto , Anciano , Antivirales/uso terapéuticoRESUMEN
Rituximab is an anti-CD20 chimeric murine/human mAb mainly used to treat certain types of lymphoproliferative malignancies and autoimmune diseases. Although it has been used in the treatment of vasculitis in recent years, it rarely triggers severe vascular skin reactions such as leukocytoclastic vasculitis (LCV). Physicians should be aware of this rare adverse event that requires discontinuation of rituximab, which can occur days or even weeks after rituximab treatment. Here, we report a case of LCV observed in a patient with low-grade orbital B-cell lymphoma treated with weekly rituximab and local radiotherapy. In our case, discontinuation of rituximab and initiation of oral methylprednisolone therapy were sufficient to achieve complete resolution of the LCV.
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Linfoma de Células B , Neoplasias Orbitales , Rituximab , Vasculitis Leucocitoclástica Cutánea , Humanos , Rituximab/efectos adversos , Vasculitis Leucocitoclástica Cutánea/inducido químicamente , Vasculitis Leucocitoclástica Cutánea/patología , Linfoma de Células B/tratamiento farmacológico , Neoplasias Orbitales/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , LinfomaRESUMEN
OBJECTIVES: In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials. METHODS: Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab. The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires. RESULT: Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years. At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions. CONCLUSIONS: After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.
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Ciclofosfamida , Síndrome de Fatiga Crónica , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Estudios de Seguimiento , Femenino , Masculino , Adulto , Persona de Mediana Edad , Síndrome de Fatiga Crónica/tratamiento farmacológico , Método Doble Ciego , Medición de Resultados Informados por el Paciente , Resultado del TratamientoRESUMEN
BACKGROUND: Immunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD. METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects. RESULTS: The analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy. CONCLUSIONS: MMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.
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Enfermedades Autoinmunes , Inmunosupresores , Enfermedades Pulmonares Intersticiales , Metaanálisis en Red , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Piridonas/uso terapéutico , Piridonas/efectos adversos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Resultado del Tratamiento , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Ácido Micofenólico/uso terapéutico , Indoles/uso terapéutico , Indoles/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Patients being on immunosuppressive treatment of any reason, along with other risk factors such as smoking and obesity, are vulnerable to be infected from SARS-CoV2. Aim of this report is to describe a case of a female patient under Rituximab therapy who experienced episodes of lung infection due to Severe Acute Coronavirus 2 (SARS-CoV-2 ) invasion although fully vaccinated. CASE REPORT: A 50-year-old woman, with a past medical history of lupus nephritis on rituximab was diagnosed with lung infection due to SARS-CoV-2. Eight months later, following her last infusion of Rituximab (RTX), she developed moderate Coronavirus Disease 2019 (COVID-19). After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and a decision was made to restart rituximab. CONCLUSIONS: This case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus in a patient with SLE and Rituximab therapy. We emphasize a precise consideration of management of patients with autoimmune disorders during the COVID-19 pandemic.
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COVID-19 , Lupus Eritematoso Sistémico , Rituximab , SARS-CoV-2 , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Femenino , COVID-19/complicaciones , Persona de Mediana Edad , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversosRESUMEN
Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4 , Rituximab , Trasplante Homólogo , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Niño , Femenino , Masculino , Preescolar , Estudios Retrospectivos , Adolescente , Herpesvirus Humano 4/inmunología , Lactante , Trasplante Homólogo/efectos adversos , Factores de Riesgo , Trastornos Linfoproliferativos/prevención & control , Trastornos Linfoproliferativos/etiología , Carga Viral , Resultado del TratamientoRESUMEN
OBJECTIVE: There is limited evidence on which immunosuppressive agents produce the best outcomes for adult patients with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS). This review compares the remission rate and adverse effects of various immunosuppressants used. METHODS: Studies of adult patients with biopsy-proven SDNS/FRNS, administered any immunosuppressive agents and reported complete remission results as one of the clinical outcomes were included. Articles were independently screened by two researchers. ROBINS-I was used for risk of bias assessment. Random-effects model was used for statistical analysis and corresponding 95% confidence intervals (CIs) were calculated. RESULTS: 574 patients across 28 studies were included in the analysis. Patients receiving rituximab have a complete remission rate of 89% (95% CI = 83% to 94%; τ2 = 0.0070; I2 = 62%; overall p < 0.01, low certainty) and adverse event rate of 0.26, cyclosporine (CR 40%; 95% CI = 21% to 59%; τ2 = 0.0205; I2 = 55%; overall p = 0.08, low certainty), tacrolimus (CR 84%; 95% CI = 70% to 98%; τ2 = 0.0060; I2 = 33%; overall p = 0.21, moderate certainty), mycophenolate mofetil (CR 82%; 95% CI = 74% to 90%; τ2 < 0.0001; I2 = 15%; overall p = 0.32, moderate certainty) and cyclophosphamide (CR 79%; 95% CI = 69% to 89%; τ2 = 0; I2 = 0%; overall p = 0.52, moderate certainty). CONCLUSION: Among the commonly used immunosuppressive agents, only rituximab has a statistically significant effect in achieving complete remission among patients with SDNS/FRNS and has a relatively good safety profile, but this is limited by low quality of evidence with high degree of heterogeneity causing a lack of statistical power.
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Inmunosupresores , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Adulto , Recurrencia , Rituximab/uso terapéutico , Rituximab/efectos adversos , Esteroides/uso terapéutico , Esteroides/efectos adversos , Terapia de Inmunosupresión , Inducción de Remisión , Resultado del TratamientoRESUMEN
INTRODUCTION: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. OBJECTIVE: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. METHODS: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. RESULTS: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). CONCLUSION: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.