Unfavorable impact of anti-rituximab antibodies on clinical outcomes in children with complicated steroid-dependent nephrotic syndrome.
BACKGROUND
Anti-rituximab antibodies (ARA) are associated not only with adverse events, such as infusion reactions (IR) and serum sickness, but also with rituximab efficacy. However, the clinical relevance of ARA in children with steroid-dependent nephrotic syndrome (SDNS) remains unknown.


METHODS
We retrospectively reviewed clinical outcomes of 13 children with complicated SDNS receiving repeated single-dose rituximab treatments at 375 mg/m2 to assess whether ARA formation could impact toxicity and efficacy of additional rituximab. Pre-rituximab 22 samples collected from patients who developed IR during the second or subsequent rituximab doses were measured by electrochemiluminescence analysis.


RESULTS
ARA were identified in 5 of 13 patients (9 of 22 samples). Median time to recovery of CD19+ B cells to > 1% of total lymphocytes and median relapse-free time after rituximab treatment were significantly shorter in the 9 ARA-positive samples than the 13 ARA-negative samples (41 vs. 100 days, p < 0.01 and 119 vs. 308 days, p < 0.05, respectively). Kaplan-Meier analysis showed that time to CD19+ B cell recovery after rituximab was significantly shorter in ARA-positive samples than in ARA-negative samples (p < 0.005). Severe IR developed in two ARA-positive patients and serum sickness in one ARA-positive patient.


CONCLUSIONS
The incidence of ARA formation was high in the pre-rituximab samples of patients with complicated SDNS who developed IR during the second or subsequent rituximab doses, suggesting that ARA formation might have an unfavorable impact on the toxicity and efficacy of additional rituximab doses in these patients.
['Fujinaga|Shuichiro|S|0000-0002-2957-3705', 'Nishino|Tomohiko|T|', 'Endo|Shota|S|', 'Umeda|Chisato|C|', 'Watanabe|Yoshitaka|Y|', 'Nakagawa|Mayu|M|']
D000906:Antibodies D018941:Antigens, CD19 D001402:B-Lymphocytes D002648:Child D002675:Child, Preschool D004342:Drug Hypersensitivity D004351:Drug Resistance D005260:Female D005938:Glucocorticoids D006801:Humans D015994:Incidence D007223:Infant D007262:Infusions, Intravenous D008297:Male D009404:Nephrotic Syndrome D012189:Retrospective Studies D000069283:Rituximab D012720:Severity of Illness Index
Anti-rituximab antibody Steroid-dependent nephrotic syndrome Infusion reactions Serum sickness Rituximab Electrochemiluminescence analysis