Implementation and Evaluation of a 90-Minute Rituximab Infusion Protocol at the Richard L. Roudebush VA Medical Center

Rituximab is a genetically engineered chimeric immunoglobulin G1 monoclonal antibody. It functions by binding to the CD20 antigen on the surface of B-cell lymphocytes, leading to complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity.¹ The US Food and Drug Administration approved this therapy to treat patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, along with other nonmalignant indications, including pemphigus vulgaris and rheumatoid arthritis (RA). Historically, a significant amount of time and labor on behalf of medical personnel has been required to administer rituximab according to the original manufacturer’s labeling due to the boxed warning associated with infusion-related reactions (IRRs).²

Originally, the elongated infusion times that were recommended for rituximab were largely due to the perceived risk of serious infusion-related adverse drug reactions. Slower infusion times should reduce the risk of a reaction and are considered to be a good option for those patients who are at a high risk of having a severe IRRs to rituximab. Examples of high-risk patients from previous studies include those with significant cardiovascular disease, a circulating lymphocyte count ≤ 5,000/µL at the start of infusion, and those who have previously had a reaction to rituximab.^3-5 In appropriate patients, research has shown a decreasing incidence of all-grade IRRs for patients who are prescribed rituximab as they receive more doses of the drug.^2,6 The ability to identify suitable patients for 90-minute infusions of rituximab and the prospect of better health system resource utilization has led investigators to study the effects of shortened infusion times.

The RATE trial addressed this subject with a phase 3 safety study on the effects of a 90-minute rituximab infusion for patients with previously untreated diffuse large B-cell and follicular lymphoma.³ The patients in this study received their first dose of rituximab using the traditional infusion approach. If it was well-tolerated, they received subsequent rituximab infusions using a 90-minute protocol. Only 1.1% of patients who had previously received a rituximab infusion developed a grade 3 or 4 IRR when receiving a faster infusion of the drug for the first time.³ This result led to the addition of instructions for a 90-minute infusion to the package insert.²

In contrast to the RATE trial, the RATE-RA trial evaluated the incidence of IRRs in patients who received rituximab for nonmalignant indications. This study assessed patients with RA receiving rituximab for > 120 minutes. The authors reported 0.6% of the patients in the study developed a grade 3 or 4 IRR associated with the first 120-minute infusion of the medication.⁵ The researchers concluded that rituximab can be administered at a faster rate during second and subsequent infusions in patients who have been shown to tolerate traditional infusions without increasing the risk or severity of IRRs.⁵

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana, uses traditional directions for the infusion of rituximab due to perceived tolerability and safety concerns specifically in a veteran population—even while other VA medical centers have implemented shortened infusion protocols. This also is despite the fact that available research shows rapid infusions of the drug are well tolerated in a variety of community settings.^7,8 Anticipated benefits of implementing a protocol include savings in chair time at the institution’s infusion clinic along with increased nursing and patient satisfaction. This project was conducted to prepare, implement, and assess the safety of a 90-minute rituximab protocol at the RLRVAMC.