Factors Influencing Infusion-Related Reactions Following Dosing of Reference Rituximab and PF-05280586, a Rituximab Biosimilar

Abstract

Background Infusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of rituximab, an anti-CD20 monoclonal antibody. Objective Our objective was to evaluate the impact of dosing/infusion patterns and certain baseline characteristics on IRR occurrence during the first rituximab infusion administered as the biosimilar PF-05280586 (RTX-PF) or reference rituximab sourced from the EU (RTX-EU, MabThera ® ) in patients with CD20+ low-tumor-burden follicular lymphoma. Patients and methods Rituximab (RTX-PF, n=196; RTX-EU, n=198) was administered (375 mg/m 2 ) on days 1, 8, 15, and 22 (one cycle), with a follow-up period through 52 weeks. The relationships between infusion rate, drug exposure, and IRR incidence were assessed by logistic regression analysis and pharmacokinetic modeling and simulation. Baseline CD20 level, antidrug antibody (ADA) status, and tumor burden according to IRR occurrence (yes/no) were compared descriptively. Results Median rituximab infusion duration on day 1 was 3.50 h for each of the two groups. There was a positive correlation between infusion rate and all-grade IRRs occurring within 24 h after infusion (p < 0.0001). Patients who developed IRRs had a higher median baseline CD20+ level. IRR incidence was unaffected by baseline ADA status. Drug exposure did not predict IRR incidence. Baseline tumor burden was similar between patients with and without IRRs. Conclusions Results of this analysis provide a better understanding of IRRs after the first rituximab (RTX-PF or RTX-EU) infusion and demonstrate a potential correlation of infusion rate and other factors with IRR at the individual and population levels. Infusion-rate escalation steps continue to be needed to manage IRRs.

Severe Hypersensitivity Reactions at Biosimilar versus Originator Rituximab Treatment Initiation, Switch and Over Time: A Cohort Study on the French National Health Data System

“…In this two-cohort study based on the French National Health Data System, we did not show an increased risk of hypersensitivity reaction associated with the injection of rituximab biosimilar compared with rituximab originator, neither in an initiation or switch context, nor for the first injection or over time. This result is consistent with clinical trials [8][9][10]35], observational studies, and systematic reviews dealing with monoclonal antibodies or fusion proteins [36][37][38][39][40][41][42], in which the authors showed no difference between the biosimilar product and originator product in terms of safety and immunogenicity, and in particular regarding hypersensitivity reactions, at either initiation or switch [16,18,43]. However, these studies were small and thus could not detect the rare events we were able to study.…”

Efficacy and safety of rituximab for primary membranous nephropathy with different clinical presentations: a retrospective study

“…This discrepancy may be due to the retrospective nature of this study, which may have resulted in the omission of some minor adverse events. In addition, the most common type of adverse reaction in previous studies was infusion reactions (7), which was relatively infrequent in the present study; this may have been due to the use of anti-allergy medication prior to infusion and the limited rate of infusion to avoid or ameliorate infusion-related events to some extent (32,33). For serious adverse events, relevant data were carefully verified in this study, and none of them were malignant or fatal.…”

Rituximab Treatment for Neuroimmunologic Disorders

“…주입관련반응 발생은 보통 주사의 주입속도, CD20+ B세포의 농도 와 관련되며 주사를 반복할수록 빈도가 감소하는 것으로 알려 져 있다 39. 스티븐스-존슨증후군, 독성표피괴사용해 등의 심한 반응은 약 10%에서 발생하는 것으로 알려져 있다 40,41.…”