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Background: Rituximab (RTX), a chimeric anti-CD20 antibody, is used in the treatment of rheumatic diseases. Infusion-related reactions (IRRs) are the most common adverse event, and premedication may reduce the incidence [1]. To date, there is still no effective predictor for the occurrence of IRRs.
Objectives: To identify factors predicting the occurrence of IRRs during the first course of RTX therapy in patients with rheumatic diseases.
Methods: We prospectively enrolled 29 patients with rheumatic diseases underwent the first course of RTX infusion, which consisted of two 500-mg intravenous infusions separated by about 2 weeks. Each patient received 100 mg intravenous methylprednisolone 60 minutes prior to each RTX infusion. Complete blood counts and C-reactive protein tests were performed before each infusion. The plasma levels of IL-1β, IL-6, IL-8, TNF-α, B-cell activating factor (BAFF) and plasma levels of myeloperoxidase (MPO)-DNA complexes were measured. All-grade IRRs occurring within 24 hours after infusions were recorded. Mann-Whitney U test was conducted to analyze factors associated with IRRs.
Results: The demographics and characteristics of the patients were shown in
The characteristics of the patients received the first course of RTX treatment (n = 29).
| Age (years) ‡ | 44.9 (38.4 to 50.9) | |
| Gender, female (%) | 26 (89.7) | |
| Diagnosis | ||
| Antiphospholipid syndrome, n (%) | 11 (37.9) | |
| Autoimmune thyroid disease, n (%) | 6 (20.7) | |
| Sjögren’s syndrome, n (%) | 4 (13.8) | |
| Systemic lupus erythematosus, n (%) | 2 (6.9) | |
| Rheumatoid arthritis, n (%) | 1 (3.4) | |
| Others, n (%) # | 5 (17.2) | |
| Blood test during each infusion | Before first infusion | Before second infusion |
| MPO-DNA complexes levels ঠ| 11% (3% to 53%) | 15% (3% to 32%) |
| IL-6 (pg/mL) ‡ | 8.3 (6.9 to 11.2) | 12.1 (8.5 to 13.8) |
| IL-8 (pg/mL) ‡ | 14.4 (12.6 to 15.9) | 13.0 (12.1 to 14.9) |
| TNF-α (pg/mL) ‡ | 8.9 (6.9 to 12.7) | 8.1 (6.1 to 11.2) |
| BAFF (pg/mL) ‡ | 155.1 (121.3 to 231.9) | 276.8 (201.3 to 331.2) |
| IL-6 (pg/mL) ‡ | 8.3 (6.9 to 11.2) | 12.1 (8.5 to 13.8) |
| Absolute neutrophil count (/μL) ‡ | 4380 (3441 to 5890) | 4360 (3286 to 8195) |
| Absolute lymphocyte count (/μL) ‡ | 1511 (1198 to 1799) | 1214 (854 to 1465) |
| C-reactive protein (mg/dL) ‡ | 0.03 (0.01 to 0.10) | 0.04 (0.02 to 0.21) |
‡ Data are presented in median and interquartile range.
# Other diagnoses include systemic sclerosis, dermatomyositis, vasculitis, pemphigus, myasthenia gravis.
¶ Data are presented in ratio to positive control.
Conclusion: Plasma MPO-DNA complexes represent neutrophil extracellular traps released by activated neutrophils. Neutrophils could be involved in the response to RTX therapy [2]. In this study, the risk of IRRs to RTX tended to increase when the plasma level of MPO-DNA complexes is low. Further research is needed to clarify the impact of activated neutrophils on RTX therapy.
REFERENCES:
[1]Paul F, Cartron G. Infusion-related reactions to rituximab: frequency, mechanisms and predictors. Expert Rev Clin Immunol. 2019 Apr; 15(4):383-389.
[2]Taylor RP, Lindorfer MA. Fcγ-receptor-mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments. Blood. 2015 Jan 29; 125(5):762-766.
Acknowledgements: This work was supported by the Ministry of Science and Technology (National Science Council) of Taiwan (Grant No. 109-2314-B-002-234 and 110-2314-B-002-244).
Disclosure of Interests: None declared