Assuntos
Comitês Consultivos/organização & administração , COVID-19/epidemiologia , Pesquisa Translacional Biomédica/organização & administração , Colorado/epidemiologia , Procedimentos Clínicos , Humanos , Disseminação de Informação , Relações Interprofissionais , Avaliação das Necessidades , Pandemias , Avaliação de Programas e Projetos de Saúde , Melhoria de QualidadeRESUMO
OBJECTIVE: To evaluate the safety, tolerability, and clinical effects of rituximab, an anti-CD20 monoclonal antibody, in the treatment of severe pediatric autoimmune diseases. STUDY DESIGN: We reviewed the records of 10 patients treated with rituximab for severe, refractory autoimmune diseases at a single tertiary care children's hospital. Adverse events as well as treatment effects were recorded. RESULTS: All patients received 4 weekly doses of rituximab at 375 mg/m2 per dose. One patient died as the result of complications of her underlying systemic lupus erythematosus 7 weeks after rituximab therapy. Three patients had serious infections, all of which resolved with standard therapy. Rituximab led to transient or sustained improvement in clinical and laboratory parameters in nine subjects. At a median follow-up of 9 months, the median prednisone dose was reduced in the responders by 0.75 mg/kg per day (mean decrease of 63%), and four patients were able to discontinue corticosteroids entirely. With longer follow-up (median, 22 months), we found that 5 of 9 patients remained clinically stable after rituximab therapy, whereas 4 patients had recurrent or new features of their underlying autoimmune disorders requiring additional corticosteroids or other immunosuppressive medications. CONCLUSIONS: Rituximab had an acceptable toxicity profile in this group of patients with severe, refractory autoimmune diseases, although there were three serious infections and one patient death. Rituximab appears to be beneficial for patients with refractory autoimmune diseases and may reduce corticosteroid exposure. Although rituximab therapy provided a durable clinical benefit for some patients in this population, other patients had reemergence of their underlying autoimmune disease.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Adolescente , Adulto , Anticorpos Monoclonais Murinos , Doenças Autoimunes/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Imunoglobulinas/sangue , Infecções/etiologia , Infusões Intravenosas , Estudos Longitudinais , Masculino , Rituximab , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effects of rituximab (anti-CD20 monoclonal antibody) on the disease course in pediatric patients with multisystem autoimmune diseases. METHODS: Four patients with multisystem autoimmune diseases refractory to conventional immunosuppressive medications, each with central nervous system (CNS) involvement, were treated with four weekly infusions of rituximab. Their clinical and laboratory responses were evaluated. RESULTS: Each of the patients had improvement in clinical symptoms and laboratory parameters. One patient with autoimmune cytopenias and autoimmune CNS and peripheral nervous system disease had resolution of the cytopenias and marked improvement in neurologic symptoms; he currently receives no immunosuppressive medications. Two half-siblings with lymphoplasmacytic colitis, pulmonary nodules, and CNS disease had improvement of their symptoms. A fourth patient with chorea and seizures secondary to primary antiphospholipid antibody syndrome had improvement in fine and gross motor function and reduced seizure frequency. There were no serious adverse events. CONCLUSIONS: The biologic response modifier rituximab, designed to eliminate B lymphocytes, was safe and effective in four pediatric patients with multisystem autoimmune disorders. It appears to be beneficial in autoimmune conditions presumably mediated by a variety of B-cell-related mechanisms, and may decrease or eliminate the need for other immunosuppressive medications.