Background/Purpose: The FDA-approved dose of rituximab (RTX) in rheumatoid arthritis (RA) is 2 × 1000 mg IV infusions given 2 weeks apart (1 course), with recommended times of 4.25 hours (h) and 3.25 h for infusions 1 and 2, respectively. The objective of this analysis was to assess the safety of administering the second infusion of a RTX course and subsequent infusions at a more rapid rate over 2 h.

Methods: Patients (pts) with moderate-to-severe RA and an inadequate response to TNF inhibitors who were either RTX-naïve or RTX-experienced (up to 2 prior courses, last course 6–9 months before baseline) were eligible. All pts received methotrexate and were premedicated with IV methylprednisolone, antihistamines and analgesics prior to all RTX infusions. All pts received the first infusion (Infusion 1) on Day 1 over 4.25 h, the standard rate. The second infusion (Infusion 2) on Day 15 was over 2 h (Infusion 1 and 2 = course 1), as were both Infusions 3 and 4 (course 2) 6 months later. The primary endpoint was the incidence of infusion-related reactions (IRRs) during or within 24 h of Infusion 2 of course 1.

Results: The 351 enrolled pts had the following characteristics: RTX-naïve (n=306; 87.2%); RTX-experienced (n=45 of which 24 [6.8%] and 21 [6.0%] had received 1 or 2 prior RTX courses, respectively); mean age 55.5 (SD 11.5) y, with 19.7% of pts aged ≥65 y; and mean RA disease duration 12.5 (SD 9.7) y. The incidence of IRRs during or within 24 h of Infusion 1 was 16.2% (95% CI 12.5%, 20.5%) (none serious), consistent with that derived from historical clinical trial data (20.7%).¹ Infusion 2 was given to 337 pts (96.0%) over 2 hours; 333 completed the infusion and received the full 1000 mg dose, 4 pts did not complete the infusion (3 for AEs [none serious], 1 for another reason). Of these 333 pts, 5 (1.5%) required an infusion time >2.5 h. The incidence of IRRs for Infusion 2 (Figure 1, primary endpoint) was 6.5% (95% CI, 4.1%, 9.7%) (22 pts experienced a total of 30 events), similar to historical data for infusion 2 given at the standard rate (8.1%).¹ All IRRs for Infusion 2 were CTC grade 1 or 2 except two grade 3 (hypertension and headache), with no grade 4 events. The most commonly observed IRRs for Infusion 2 were nausea (1.2%) and chills (0.9%). Course 2 data indicate a low incidence of IRRs for Infusions 3 (secondary endpoint) and 4. No serious IRRs or SAEs were reported during or within 24 h of Infusions 1 and 2 (course 1) or Infusions 3 and 4 (course 2).

Conclusion: The incidence of IRRs occurring during or within 24 h of the second infusion of RTX when administered at an increased 2 h rate is similar to the historical incidence. The incidence of IRRs for subsequent infusions is also similar to the historical incidence. The overall safety data were consistent with the known RTX safety profile. These data of RTX at a faster infusion rate provide clinically relevant information for HC providers and patients.

1. van Vollenhoven, et al. ACR 2012: poster 459.