A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis

The primary criterion for assessing safety of the faster infusion was the incidence of infusion related reaction (IRRs). IRRs were adverse events (AEs) that occurred within 24 hours of beginning infusion that were among a pre-specified list of preferred terms from the Medical Dictionary for Regulatory Activities (MedDRA). Incidence is defined as the percentage of participants experiencing an IRR.

Time frame: Within 24 hours of beginning infusion on Day 15

Population: All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.

The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0), where Grade 1 indicates Mild severity and Grade 5 indicates Death. The CTCAE defines Grades 3 and 4 as follows: - Grade 3 means Severe, indicating considerable interference with the patient's daily activities; medical intervention/therapy required; and hospitalization possible. - Grade 4 means Life-threatening, Disabling, based on extreme limitation in activity; significant medical intervention/therapy required, and hospitalization probable.

Time frame: Within 24 hours of beginning infusion on Day 15

Population: All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.

The intensity of AEs experienced within 24 hours of beginning infusion were graded on NCI's CTCAE (v. 4.0) intensity scale from Grade 1 (Mild) to Grade 5 (Death). Grade 3 AEs are Severe and Grade 4 AEs are Life-threatening, Disabling.

Time frame: Within 24 hours of beginning infusion on Day 168

Population: All randomized participants who received infusion at the faster rate on Day 168. One participant received the Day 168 rituximab infusion at the labeled rate rather than at the faster rate and was excluded from the analysis population.

IRRs are AEs that occurred within 24 hours of beginning infusion that were included on a pre-specified list of MedDRA preferred terms, and an SIRR is an IRR that suggests a significant hazard, contraindication, side effect or precaution.

Time frame: Within 24 hours of beginning infusion on Day 168

Population: All randomized participants who received infusion at the faster rate on Day 168. One participant received the Day 168 rituximab infusion at the labeled rate rather than at the faster rate and was excluded from the analysis population.

A serious infusion-related reaction (SIRR) is an IRR that meets the definition of a serious adverse event. A serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution.

Time frame: Within 24 hours of beginning infusion on Day 15

Population: All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.

Participants who experienced a moderate or serious IRR had their infusion interrupted immediately and received aggressive symptomatic treatment. The CTCAE includes the following severity descriptions: - Moderate means mild to moderate interference with the patient's daily activities, no or minimal medical intervention/therapy required; - Severe means considerable interference with the patient's daily activities, medical intervention/therapy required, hospitalization possible. If the IRR was moderate, the infusion was not to be restarted before all the symptoms disappeared, and then at half the rate. If the participant tolerated the reduced rate for 30 minutes, the infusion rate was increased to the next rate on the protocol-specified infusion schedule. If the symptoms did not resolve with treatment, the participant was withdrawn from the treatment period of the study. Participants who experienced a severe IRR to rituximab treatment were discontinued from the study.

Time frame: During the infusion (a 2-hour period) on Day 15

Population: All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.

Participants who experienced a moderate or serious IRR had their infusion interrupted immediately and received aggressive symptomatic treatment. The CTCAE includes the following severity descriptions: - Moderate means mild to moderate interference with the patient's daily activities, no or minimal medical intervention/therapy required; - Severe means considerable interference with the patient's daily activities, medical intervention/therapy required, hospitalization possible. If the IRR was moderate, the infusion was not to be restarted before all the symptoms disappeared, and then at half the rate. If the participant tolerated the reduced rate for 30 minutes, the infusion rate was increased to the next rate on the protocol-specified infusion schedule. If the symptoms did not resolve with treatment, the participant was withdrawn from the treatment period of the study. Participants who experienced a severe IRR to rituximab treatment were discontinued from the study.

Time frame: During the infusion (a 2-hour period) on Day 168

Population: All randomized participants who received infusion at the faster rate on Day 168. One participant received the Day 168 rituximab infusion at the labeled rate rather than at the faster rate and was excluded from the analysis population.