‘Substantial risk’ for hypogammaglobulinemia with rituximab in childhood-onset rheumatic diseases
medwireNews: In a chart review of patients with childhood-onset rheumatic diseases treated with rituximab, over a quarter developed hypogammaglobulinemia and a similar proportion had infectious complications, researchers report.
This “highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” say Mei Sing Ong (Harvard Medical School, Boston, Massachusetts, USA) and colleagues.
The study included 85 patients who received rituximab for the treatment of a childhood-onset rheumatic disease; 53 had systemic lupus erythematosus and other related diseases, 14 had vasculitis, 13 had juvenile idiopathic arthritis, four had juvenile dermatomyositis, and one had polymyositis. Patients were between 6 and 24 years of age and were treated at Boston Children’s Hospital between 2009 and 2019.
Within 18 months of rituximab induction, 27.1% of patients developed new-onset hypogammaglobulinemia – defined as a serum immunoglobulin (Ig)G level at least 2 standard deviations below the age-specific norms at the hospital – at a median of 37 days from the induction of rituximab. An additional four patients were found to have hypogammaglobulinemia before starting rituximab, in one of whom the condition worsened during the 18-month post-rituximab period.
Approximately a quarter (25.9%) of the patients developed at least one infectious complication at a median 49.5 days after starting rituximab, with half requiring inpatient treatment. The incidence of infection increased from 0.43 to 0.77 infections per 1000 person–days before versus after starting rituximab.
Multivariable analysis revealed that receipt of pulse-dose corticosteroids in the month before starting rituximab was the strongest predictor of both new-onset hypogammaglobulinemia and infections, with significant odds ratios (ORs) of 3.94 and 15.30, respectively.
“This association […] provides additional rationale for refinement of consensus treatment protocols and treat-to-target studies that focuses on reducing steroid exposure and toxicity while maintaining treatment efficacy,” comment the study authors in Rheumatology.
Younger age at rituximab use (OR=0.83) and male sex (OR=5.40) were also significantly associated with new-onset hypogammaglobulinemia, while a diagnosis of vasculitis was a significant predictor of any (OR=6.56) and serious (OR=7.13) infectious complications following rituximab use. The risk for serious infections was also significantly greater for patients who did versus did not develop hypogammaglobulinemia post-rituximab (OR=7.89).
The researchers highlight the need for larger, prospective studies “to gain a more complete understanding of the longitudinal risks and best practices for monitoring the effects of rituximab therapy and to identify risk factors in different disease populations.”
But they nevertheless believe it is “reasonable to monitor total IgG levels every 3-6 months post-rituximab for at least one year and possibly longer, particularly for younger patients, those with vasculitis, and those with exposure to pulse dose corticosteroids.”
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