B cell depletion for autoimmune diseases in paediatric patients

Abstract

Data on B cell depletion therapy in severe autoimmune diseases in paediatric patients are very limited. We conducted a retrospective cohort study and recruited patients who were treated with rituximab (RTX) and followed up for at least 6 months through the German societies of paediatric rheumatology and nephrology. The aim was to describe the spectrum of autoimmune disorders for which RTX was used and to describe the applied therapeutic regimens, the observed efficacy, as well as potential immunological side effects. The need to develop standard treatment guidelines for future trials should be discussed. Sixty-five patients were included. Nineteen patients suffered from systemic lupus erythematosus, 13 from vasculitic disorders, 12 from hematological autoimmune diseases, 5 from mixed connective tissue disorders, 4 from juvenile idiopathic arthritis, and 9 had other autoimmune diseases. Adverse, infusion-related events were reported in 12/65 (18%) patients. Considering laboratory and clinical parameters, 13 patients (22%) were in complete remission, 31 (52%) were in partial remission, 6 (10%) were unchanged and 10 (17%) had progressed after 6 months. In 46% of the patients, the steroid dose could be more than halved. IgG, IgM and IgA decreased from normal levels prior to RTX therapy to below normal levels at 6 months in 2/22 (9%), 10/21 (48%), and 4/22 (18%) patients, respectively. Immunoglobulin deficiency or prolonged CD20 depletion was reported in eight patients after an observation period longer than 12 months. RTX therapy led to a perceivable reduction in disease activity. However, long-term immunological alterations may occur in more than 10% of the patients. Guidelines and protocols for off-label therapy are desirable to document reasonable follow-up data. Controlled prospective studies for RTX therapies in children with standardised therapeutic and diagnostic protocols are urgently needed.

Safety and Efficacy of Rituximab in Childhood-onset Systemic Lupus Erythematosus and Other Rheumatic Diseases

“…Although it lacks any pediatric indications, RTX has been widely studied for various pediatric rheumatologic conditions, including autoimmune hemolytic anemia, immune thrombocytopenic purpura, systemic lupus erythematosus (SLE), vasculitis, and juvenile dermatomyositis 1,2,3,4 . The use of RTX to treat pediatric autoimmune disease has particularly focused on SLE 5,6 .…”

The development and assessment of biological treatments for children

“…Due to the uncontrolled nature of the study and the range of concomitant medications, the results should be interpreted with caution. In contrast to adults treated with rituximab, children may develop long-standing B cell depletion and hypogammaglobuminaemia requiring intravenous immunoglobulin [115].…”

Juvenile idiopathic arthritis: management and therapeutic options

“…Rituximab has been effective in many autoimmune disorders and is mostly used in severe adult RA and systemic lupus erythematosus. There are no trials assessing the use of rituximab in JIA but there are several case reports of B-cell depletion for autoimmune disease, including JIA in pediatric patients [Jansson et al 2011;El-Hallak et al 2007]. Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the brain due to polyoma virus or JC virus.…”