JMIR Publications

ABSTRACT

Background:

Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions, especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1 receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce infusion reactions. Multiple retrospective case-control studies indicate that the second-generation histamine H1 receptor antagonists might be more effective than the first-generation ones in suppressing infusion reactions caused by the rituximab infusion.

Objective:

This study aimed to assess the effects of first- and second-generation histamine H1 receptor antagonists on preventing infusion reactions resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma.

Methods:

This is a phase II, double-blind, active-controlled, and randomized trial. We aim to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will be receiving their initial rituximab infusion. Participating patients will be administered with hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1 receptor antagonist, respectively. This will be combined with 400 mg acetaminophen tablets taken approximately 30 min before the first infusion of rituximab. The primary endpoint of this trial is to assess severe infusion reactions occurring within a 4-h period after the initiation of rituximab infusion, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 as the basis for estimation. Additionally, the trial will evaluate histamine H1 receptor antagonists-induced drowsiness using the visual analogue scale, with each patient providing their individual response as a secondary endpoint.

Results:

This study began with patient recruitment in April 2023, with 17 subjects enrolled as of November 12th, 2023. The anticipated study completion is set for February 2025.

Conclusions:

This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1 receptor antagonist in preventing infusion reactions induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase Ⅲ study aimed at determining the standard premedication protocol for rituximab infusion. Clinical Trial: Japan Registry of Clinical Trials (jRCT) jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169.