Safety of Accelerated Rituximab Infusion in Rheumatic Diseases: A Systematic Review

To systematically evaluate the safety and feasibility of rapid rituximab (RTX) infusion protocols in patients with autoimmune rheumatic diseases.

A comprehensive literature review was conducted using PubMed, LILACS, and Scielo databases from 1965 to May 2024 without language restrictions. Studies reporting infusion reactions associated with accelerated RTX protocols (infusion over 90 to 120 min) in rheumatologic conditions were included. Infusion-related adverse events were assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Grades 1-5). Key variables extracted included patient demographics, underlying diseases, RTX dosage, use of premedication, number of infusions, and frequency and severity of infusion reactions.

Seven studies encompassing 538 patients aged 14-78 years were included. The patient cohort covered a spectrum of autoimmune rheumatic conditions, including systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, Sjögren's syndrome, systemic sclerosis, IgG4-related disease, and anti-synthetase syndrome. All studies implemented rapid RTX infusion protocols exclusively for the second and subsequent doses. Premedication with acetaminophen, diphenhydramine, and corticosteroids was routine in most studies. RTX dosage varied between 375 mg/m² and 1000 mg, administered in two infusions spaced two weeks apart. The incidence of infusion reactions ranged from 3 to 15%, predominantly of mild severity (Grades 1 and 2), with only six cases classified as Grade 3. No Grade 4 or 5 reactions were reported. Rapid infusion protocols consistently reduced the total time patients spent in infusion clinics.

Rapid infusion of RTX in patients with autoimmune rheumatic diseases appears to be a safe and efficient alternative to standard infusion protocols. The frequency and severity of infusion reactions were comparable to traditional infusion rates, with the added benefit of reduced clinic time. These findings support the broader implementation of rapid infusion protocols in rheumatology. However, larger prospective studies with standardized reporting of adverse events are necessary to validate these results and explore the feasibility of even shorter infusion durations, as seen in oncology.