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1.
BMJ Case Rep ; 14(10)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625443

RESUMO

A 50-year-old Indian woman presented with acute dysphasia, left upper limb numbness and thrombocytopenia 12 days after receiving the ChAdOx1 nCoV-19 vaccine (AstraZeneca/Vaxzevria). MRI of the brain was unremarkable. Microangiopathic haemolytic anaemia with thrombocytopenia was noted on her peripheral blood film. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was confirmed through the findings of absent ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity and markedly raised titre of ADAMTS13 autoantibodies. Prompt treatment with plasma exchange, adjunctive steroids and rituximab was commenced. A remission of TTP was achieved and she was discharged 3 weeks after admission. While other immune-mediated conditions have been documented after receipt of the vaccine, this report highlights the first case of immune-mediated TTP diagnosed after administration of the ChAdOx1 nCoV-19 vaccine.


Assuntos
Púrpura Trombocitopênica Trombótica , Vacinas , Vacinas contra COVID-19 , Feminino , Humanos , Pessoa de Meia-Idade , Troca Plasmática , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/efeitos adversos
2.
Ann Palliat Med ; 10(9): 9660-9668, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628891

RESUMO

BACKGROUND: The main aim of this study was to determine some simple but meaningful parameters that indicate immunochemotherapy-related interstitial lung disease (ILD) early in B-cell lymphoma and provide direction to hematologists. METHODS: The clinical and laboratory characteristics, the treatments and outcomes of 21 B-cell lymphoma patients with ILD who underwent rituximab (RTX) -based immunochemotherapy were collected and retrospectively analyzed. RESULTS: More cycles of immunochemotherapy and higher cumulative doses of RTX and doxorubicin hydrochloride liposome conferred a high risk of ILD. Compared to the baseline, patients had a significantly lower white blood cell count (WBC), absolute lymphocyte count (ALC), and albumin level (4.95×109 vs. 6.32×109, 0.71×109 vs. 1.61×109, 34.1 vs. 40.4 g/L; P<0.05), and higher C-reactive protein (CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH), and lactate dehydrogenase (LDH) (15.36 vs. 7.00 mg/L, 293.0 vs. 163.1 U/L, 361.8 vs. 231.1 U/L; P<0.05) levels at ILD onset. Further, a positive correlation was found between early glucocorticosteroid intervention and the good prognostication of ILD. In addition, an analysis of the prognoses of 2 cases of patients with pneumocystis pneumonia (PCP) infection indicated that after 3 cycles of treatment, patients, especially unfit patients or those who have received ILD glucocorticoid treatment, may need to receive trimethoprim/sulfamethoxazole (TMP/SMX) to prevent PCP. CONCLUSIONS: There was a relationship between variations of blood parameters and the occurrence of ILD which might serve as a warning for B-cell lymphoma patients with immunochemotherapy-related ILD.


Assuntos
Doenças Pulmonares Intersticiais , Linfoma de Células B , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Linfoma de Células B/tratamento farmacológico , Estudos Retrospectivos , Rituximab/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol
3.
Blood Adv ; 5(17): 3354-3361, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477816

RESUMO

Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10-treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.


Assuntos
Medicamentos Biossimilares , Linfoma Folicular , Anticorpos Monoclonais Murinos , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Rituximab/efeitos adversos
4.
Rheumatol Int ; 41(10): 1839-1843, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34409510

RESUMO

The outcomes of COVID-19 in patients treated with biologic agents are a subject of intense investigation. Recent data indicated that patients under rituximab (RTX) may carry an increased risk of serious disease. We performed an electronic search in Medline and Scopus using the keywords rituximab and COVID-19. We present a rare case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following RTX treatment. In a relevant literature search, we identified 18 cases of patients with rheumatic diseases (6 RA, 8 ANCA vasculitis, 3 systemic sclerosis and 1 polymyositis) treated with RTX who experienced an atypical and/or prolonged course of COVID-19 pneumonia with no evidence of cytokine storm. Our case indicates that RTX may unfavorably affect outcomes following SARS-CoV-2 infection. B cell depletion may dampen the humoral response against the virus; we may hypothesize that B cell-depleted patients may be protected from cytokine storm but on the other hand may have difficulties in virus clearance leading to a protracted course. Taking into account that COVID-19 vaccines are available we may consider delaying RTX infusions at least in patients without life threatening disease, until vaccination is completed.


Assuntos
Antirreumáticos/efeitos adversos , COVID-19/imunologia , Contraindicações de Medicamentos , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Rituximab/efeitos adversos , Idoso , Antirreumáticos/administração & dosagem , COVID-19/diagnóstico , Evolução Fatal , Feminino , Humanos , Infusões Intravenosas , Masculino , Rituximab/administração & dosagem , SARS-CoV-2
5.
Int J Clin Pharmacol Ther ; 59(10): 645-653, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34338191

RESUMO

OBJECTIVE: The aim of the present study was to compare the effectiveness and safety of rituximab, mycophenolate mofetil (MMF), and cyclophosphamide (CYC) for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We conducted a Bayesian network meta-analysis to incorporate direct and indirect data from six randomized controlled trials (comprising 541 patients) that investigated the effectiveness and safety of rituximab, MMF, and CYC for the treatment of patients with AAV and met the inclusion criteria. RESULTS: Rituximab and MMF demonstrated a trend toward a higher response rate than CYC, (OR 1.41, 95% credible interval (CrI) 0.84 - 2.40) and (OR 1.20, % CrI 0.73 - 1.93), respectively. The surface under the cumulative ranking curve (SUCRA) revealed that rituximab has the highest probability of being a better remission-induction therapy (SUCRA = 0.797), followed by MMF and CYC (-SUCRA = 0.537 and 0.166, respectively). However, CYC displayed a propensity for a lower relapse than rituximab and MMF (OR 0.81, 95% CrI 0.42 - 1.50; OR 0.72, % CrI 0.39 - 1.27), further confirmed by -SUCRA rankings. Rating likelihood based on -SUCRA revealed that rituximab was more likely to be the safest medication since it displayed a lower incidence of serious adverse effects (SAEs), followed by CYC and MMF. CONCLUSION: Rituximab may serve as an effective remission-induction therapy for patients with AAV and decrease the incidence of SAEs. Although rituximab showed a high relapse rate, the accompanying desirable safety profile indicates that it is the first therapeutic choice for patients with AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Teorema de Bayes , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Funções Verossimilhança , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Rituximab/efeitos adversos , Resultado do Tratamento
6.
BMC Womens Health ; 21(1): 285, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353326

RESUMO

BACKGROUND: Consequences of long-term B cell depletion with rituximab are not well understood. We describe inflammatory vaginitis as a potential side effect of long-term rituximab treatment, distinct from previously described vulvovaginal pyoderma gangrenosum. METHODS: We performed a retrospective analysis of women treated with rituximab for more than 1 year to determine the prevalence and clinical characteristics of vaginitis cases. We conducted a case-control analysis with up to 3 controls for each vaginitis case. RESULTS: We identified sixteen inflammatory vaginitis cases. Women with vaginitis were age 23-68 (median 42), primarily being treated for ANCA-associated vasculitis (11/16; 69%). Most reported copious vaginal discharge (100%) and pain with sex (75%). All women with return of circulating B-cells to > 10 cells/mL had complete (5/9) or significant (4/9) improvement in symptoms. In case-control analysis there was no significant difference in length of B-cell depletion, immune parameters, creatinine levels, and history of neutropenia. CONCLUSION: Inflammatory vaginitis is a potential side effect of prolonged continuous B cell depletion with rituximab. More studies are needed to characterize the incidence and etiology of vaginitis among women on long term rituximab therapy and establish a causal relationship.


Assuntos
Doenças Autoimunes , Descarga Vaginal , Vaginite , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/efeitos adversos , Vaginite/tratamento farmacológico , Vaginite/epidemiologia , Adulto Jovem
7.
BMJ Case Rep ; 14(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244190

RESUMO

A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 µmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.


Assuntos
Hepatite B , Falência Hepática , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/uso terapêutico , Vírus da Hepatite B , Humanos , Masculino , Rituximab/efeitos adversos , Ativação Viral
8.
J Med Case Rep ; 15(1): 339, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34233732

RESUMO

BACKGROUND: Rituximab is a novel chimeric monoclonal antibody that has established itself as a potent therapeutic option for autoimmune medical conditions, including systemic lupus erythematosus, owing to its mechanism of action targeting CD20 cells. Rituximab is also known to cause a spectrum of side effects including hematological abnormalities. Acute isolated thrombocytopenia following rituximab is an uncommon occurrence and, when seen, occurs in the presence of underlying hematological malignancies. Its occurrence in autoimmune diseases is rare. Despite this, acute isolated thrombocytopenia in the backdrop of systemic lupus erythematosus is undocumented. CASE PRESENTATION: A young 36-year-old South Asian female with systemic lupus erythematosus with class IV lupus nephritis poorly responding to standard therapy was initiated on rituximab. Ten days later, she presented with mucocutaneous bleeding and ecchymotic skin lesions. Isolated severe thrombocytopenia was noted with a platelet count of 5 × 109/L (150-450). Anticipating life-threatening bleeding, she was given intravenous immunoglobulin, methyl prednisolone, and platelet transfusion considering a spectrum of initial differential diagnosis. Rituximab was also withheld. Though extensively investigated, most investigations were negative. A platelet destructive process was suspected as bone marrow biopsy showed adequate megakaryocytes. Weighing the risk versus benefit, following recovery, she was reinitiated on rituximab. Within 4 days, she presented again with similar symptoms and severe isolated thrombocytopenia was noted. Rituximab-induced acute thrombocytopenia was considered the working clinical diagnosis. CASE DISCUSSION AND CONCLUSION: Rituximab can cause a spectrum of hematological abnormalities, including isolated acute thrombocytopenia. Its occurrence in autoimmune conditions is rare, and its manifestation in systemic lupus erythematosus is undocumented. Its exact etiology is still disputed. Usually considered benign, the platelet numbers tend to show improvement with cessation of therapy. However, in the presence of mucocutaneous bleeding in our patient, we took an aggressive approach to management. Though evidence for corrective therapy is anecdotal, it could be justified on the basis of averting potential catastrophic hemorrhagic manifestations. The spectrum of autoimmune disease that potentially predisposes rituximab to cause thrombocytopenia should be extended to include systemic lupus erythematosus.


Assuntos
Lúpus Eritematoso Sistêmico , Trombocitopenia , Adulto , Anticorpos Monoclonais , Antígenos CD20 , Feminino , Humanos , Rituximab/efeitos adversos
9.
Ann Clin Transl Neurol ; 8(8): 1738-1744, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240579

RESUMO

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , COVID-19/fisiopatologia , Fatores Imunológicos/farmacologia , Interferons/farmacologia , Esclerose Múltipla/tratamento farmacológico , Rituximab/farmacologia , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/epidemiologia , Feminino , França/epidemiologia , Humanos , Fatores Imunológicos/efeitos adversos , Interferons/efeitos adversos , Itália/epidemiologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Análise Multivariada , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Índice de Gravidade de Doença
11.
Lancet Haematol ; 8(8): e593-e604, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34329579

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a serious and usually fatal CNS infection caused by the John Cunningham virus. CD4+ and CD8+ T-cell lymphopenia, resulting from HIV infection, chemotherapy, or immunosuppressive therapy, are primary risk factors for PML. Following its introduction in 1997, the immunomodulatory anti-CD20 monoclonal antibody, rituximab, has received regulatory approval worldwide for treatment of non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukaemia, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulagris. Rituximab leads to prolonged B-lymphocyte depletion, potentially allowing John Cunningham viral infection to occur. Six unexpected cases of PML infection developing in rituximab-treated patients were first reported in 2002. We review 20 years of information on clinical findings, pathology, epidemiology, proposed pathogenesis, and risk-management issues associated with PML infection developing after rituximab treatment. Since the first case series report of 52 cases of rituximab-associated PML among patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia in 2009, updated and diligent pharmacovigilance efforts have provided reassurance that this fatal toxicity is a rare clinical event with concurring causal factors. International harmonisation of safety warnings around rituximab-associated PML should be considered, with these notifications listing rituximab-associated PML under a section titled warnings and precautions as is the case in most countries, rather than a boxed warning as is the case in the USA.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Neoplasias/tratamento farmacológico , Rituximab/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Prognóstico
12.
Immunopharmacol Immunotoxicol ; 43(5): 507-518, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34287098

RESUMO

BACKGROUND: Rituximab is a FDA-approved monoclonal antibody for adults with moderate to severe potentially life-threatening pemphigus vulgaris. Recent studies have focused on assessments of efficacy and safety of low-dose rituximab (<2 gram in each cycle). METHOD: Databases were searched from 2010 to 2020 (last update: 1 June 2020). RESULT: Nine studies were entered; including180 cases (92: women, 88: men, age range: 9-83 years). The dosages of each Rituximab cycle varied between ultra-low-dose (≤500 mg for a cycle, either multiple infusions or a single infusion), low-dose (2 × 375 mg/m2 or 2 × 500 mg) and modified-dose (3 × 375 mg/m2 or 3 × 500 mg). The efficacy and safety of Rituximab in the studies are known by the recovery time, relapse time, and side events. According to the studies, 2 × 500 can lead to complete remission in a broad range, from 35 to 82%. These differences might be explained by different end-points and variable cumulative corticosteroid dosage after RTX administration. Although the studies showed that low dose RTX is efficient, there are some controversies regarding the choosing low-dose for severe patients. CONCLUSION: Considering the effectiveness of low-dose, intermediate dose, and ultra-low-dose protocols of Rituximab in inducing remission in pemphigus disease and considering factors such as cost of therapy, and the need to induce a minimum of immunosuppression for a minimum duration in the COVID-19 pandemic, suggested to use low-dose Rituximab protocol (2 infusions of 500 mg Rituximab: interval of 2 weeks) to induce the remission in mild-to-moderate pemphigus patients.


Assuntos
COVID-19/imunologia , Hospedeiro Imunocomprometido , Fatores Imunológicos/administração & dosagem , Pênfigo/tratamento farmacológico , Rituximab/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/virologia , Criança , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pênfigo/diagnóstico , Pênfigo/imunologia , Indução de Remissão , Fatores de Risco , Rituximab/efeitos adversos , SARS-CoV-2/imunologia , Resultado do Tratamento , Adulto Jovem
13.
Int J Clin Pract ; 75(10): e14685, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34331726

RESUMO

AIMS: Hepatitis B virus (HBV) infection is a worldwide distributing viral disease. Hepatitis caused by HBV reactivation may progress to chronic illness and associated with increased risk of hepatic failure and hepatocellular cancer. Rituximab (RTX) is an immunosuppressive agent, is particularly used in the treatment of non-Hodgkin's Lymphoma. Patients have significant risk for HBV reactivation following chemotherapy with a RTX-containing regimen. This study aimed to determine the HBV screening manner and reactivation rates in patients with haematological neoplasm following chemotherapy including Rituximab. METHODS: This is a single-centered retrospective cohort study. A total of 331 adults with haematological disorders who received chemotherapy regimen including RTX between years of 2006 and 2016 were enrolled. Patients who experienced reactivation were evaluated. RESULTS: Only 130 of 331 patients were screened appropriately for HBV infection for 10-year period. We found 18 patients were Hepatitis B surface antigen (HBsAg) (+) and 16 (88.8%) of them received antiviral prophylaxis. Among screened patients, 27 were HBsAg (-)/AntiHBc (+) and only 10 (37%) of them received HBV prophylaxis. In total, nine patients experienced reactivation, six were from screened and three were from unscreened group. CONCLUSION: Incomplete screening and inappropriate prophylaxis may result in HBV reactivation in patients under RTX-based chemotherapy and related complications such as death.


Assuntos
Hepatite B , Ativação Viral , Adulto , Hepatite B/induzido quimicamente , Hepatite B/diagnóstico , Antígenos de Superfície da Hepatite B , Humanos , Estudos Retrospectivos , Rituximab/efeitos adversos
14.
Mult Scler Relat Disord ; 54: 103143, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34273608

RESUMO

OBJECTIVE: Rituximab (RTX), an anti-CD20 monoclonal antibody, has been demonstrated to be a useful maintenance therapy for neuromyelitis optica spectrum disorder (NMOSD). However, few patients may suffer from relapses shortly after RTX. In order to investigate the clinical features of RTX-related relapses and guide therapeutic strategy, 3 patients in our department were reported and literatures were reviewed. METHODS: We reported three NMOSD patients suffered from relapses shortly after rituximab treatment in our hospital and reviewed 13 patients reported in literatures. Their demographic characteristics, clinical features and therapeutic strategy were retrospectively analyzed. RESULTS: Sixteen patients, including three cases reported in this study, experienced 21 attacks within 1 month after RTX infusion. All of them were women with an age at onset of 34.0 ± 15.0 years. Fourteen patients were seropositive for aquaporin-4 antibody, and one was seropositive for myelin oligodendrocyte glycoprotein antibody. 57.1% (12/21) of RTX-related relapses occurred after the first use of RTX. Their clinical manifestations included optic neuritis (8/21), myelitis (11/21), and the other two relapses without detailed descriptions. Also, 62.5% (10/16) of patients had a history of prior relapses within 3 months before RTX infusions, and the location of nine relapses overlapped with previous relapses. RTX was given again after the first RTX-related relapse in eight patients, three of them with low-dosage RTX stayed stable for years, and five patients with full-dosage RTX experienced another RTX-related relapse. CONCLUSIONS: Relapses may occur shortly after RTX treatment in NMOSD. RTX-related relapse did not necessarily mean that RTX was ineffective in low-dosage regimen. Timely and sufficient treatment of RTX is crucial to prevent a relapse. It may be more reasonable to monitor B cell repopulation so as to determine a re-treatment regimen. RTX-related relapse following full-dosage RTX may be a predictor for a second time RTX-related relapse and it may be reasonable to switch to other immunosuppressants in early stage.


Assuntos
Neuromielite Óptica , Neurite Óptica , Aquaporina 4 , Feminino , Humanos , Neuromielite Óptica/tratamento farmacológico , Recidiva , Estudos Retrospectivos , Rituximab/efeitos adversos
16.
Front Immunol ; 12: 711915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276706

RESUMO

Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. She was unable to establish an adequate antiviral immune response because of previous chemotherapy, including the infusion of the anti-CD20 monoclonal antibody rituximab, administered to treat a diffuse large B-cell lymphoma. The disease promptly recovered despite evidence of no endogenous anti-SARS-CoV-2 antibody production. The observation that passive antibody therapy might prove particularly effective in immunodepressed COVID-19 patients requires evaluation in prospective randomized controlled trial.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Imunização Passiva/métodos , Hospedeiro Imunocomprometido , Imunoglobulina G/uso terapêutico , Plasmaferese/métodos , SARS-CoV-2/genética , Antineoplásicos Imunológicos/efeitos adversos , Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , RNA Viral/genética , Rituximab/efeitos adversos , Resultado do Tratamento
18.
N Engl J Med ; 384(24): 2295-2305, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34097368

RESUMO

BACKGROUND: Rituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials. METHODS: In a randomized, controlled trial, we assigned patients with moderate-to-severe pemphigus vulgaris in a 1:1 ratio to receive intravenous rituximab (1000 mg on days 1, 15, 168, and 182) or oral mycophenolate mofetil (2 g per day), in addition to an oral glucocorticoid administered on the same tapering schedule in the two groups. The primary end point was sustained complete remission at week 52, defined as the healing of lesions with no new active lesions, as reflected by a Pemphigus Disease Area Index (PDAI) activity score of 0 (on a scale of 0 to 250, with higher scores indicating greater disease severity), for at least 16 weeks without the use of glucocorticoids. Secondary end points were the cumulative dose of glucocorticoids, the number of disease flares, and the change from baseline in the score on the Dermatology Life Quality Index (DLQI; scores range from 0 to 30, with higher scores indicating greater impairment). RESULTS: Of the 135 patients who underwent randomization, 67 were assigned to receive rituximab and 68 to receive mycophenolate mofetil. The primary outcome was assessed in the modified intention-to-treat population: 62 patients in the rituximab group and 63 in the mycophenolate mofetil group. The median PDAI activity scores at baseline were 22.7 in the rituximab group and 18.3 in the mycophenolate mofetil group. At week 52, sustained complete remission was observed in 25 patients (40%) in the rituximab group and in 6 (10%) in the mycophenolate mofetil group (difference, 31 percentage points; 95% confidence interval [CI], 15 to 45; P<0.001). The mean cumulative glucocorticoid dose during the 52-week treatment period was 3545 mg in the rituximab group and 5140 mg in the mycophenolate mofetil group (difference, -1595 mg; 95% CI, -2838 to -353; P<0.001). There were 6 disease flares in the rituximab group and 44 in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05 to 0.29; P<0.001). The mean change in DLQI score was -8.87 points and -6.00 points, respectively (difference, -2.87 points; 95% CI, -4.58 to -1.17; P = 0.001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group. CONCLUSIONS: Rituximab was superior to mycophenolate mofetil in producing sustained complete remission at 52 weeks in patients with pemphigus vulgaris. Rituximab resulted in a greater reduction in glucocorticoid use than mycophenolate mofetil, but more patients in the rituximab group had serious adverse events. Further trials are needed to determine the comparative efficacy and safety of rituximab and mycophenolate mofetil beyond 52 weeks of treatment. (Funded by F. Hoffmann-La Roche; PEMPHIX ClinicalTrials.gov number, NCT02383589.).


Assuntos
Ácido Micofenólico/uso terapêutico , Pênfigo/tratamento farmacológico , Rituximab/uso terapêutico , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Indução de Remissão , Rituximab/efeitos adversos
20.
BioDrugs ; 35(4): 459-468, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34152584

RESUMO

BACKGROUND: Infusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of rituximab, an anti-CD20 monoclonal antibody. OBJECTIVE: Our objective was to evaluate the impact of dosing/infusion patterns and certain baseline characteristics on IRR occurrence during the first rituximab infusion administered as the biosimilar PF-05280586 (RTX-PF) or reference rituximab sourced from the EU (RTX-EU, MabThera®) in patients with CD20+ low-tumor-burden follicular lymphoma. PATIENTS AND METHODS: Rituximab (RTX-PF, n=196; RTX-EU, n=198) was administered (375 mg/m2) on days 1, 8, 15, and 22 (one cycle), with a follow-up period through 52 weeks. The relationships between infusion rate, drug exposure, and IRR incidence were assessed by logistic regression analysis and pharmacokinetic modeling and simulation. Baseline CD20 level, antidrug antibody (ADA) status, and tumor burden according to IRR occurrence (yes/no) were compared descriptively. RESULTS: Median rituximab infusion duration on day 1 was 3.50 h for each of the two groups. There was a positive correlation between infusion rate and all-grade IRRs occurring within 24 h after infusion (p < 0.0001). Patients who developed IRRs had a higher median baseline CD20+ level. IRR incidence was unaffected by baseline ADA status. Drug exposure did not predict IRR incidence. Baseline tumor burden was similar between patients with and without IRRs. CONCLUSIONS: Results of this analysis provide a better understanding of IRRs after the first rituximab (RTX-PF or RTX-EU) infusion and demonstrate a potential correlation of infusion rate and other factors with IRR at the individual and population levels. Infusion-rate escalation steps continue to be needed to manage IRRs. TRIAL REGISTRATION (DATE OF REGISTRATION): ClinicalTrials.gov Identifier: NCT02213263 (11 August 2014); and EudraCT: 2014-000132-41 (10 October 2014).


Assuntos
Antineoplásicos , Medicamentos Biossimilares , Anticorpos Monoclonais , Antígenos CD20 , Antineoplásicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Humanos , Rituximab/efeitos adversos
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