This study was designed to evaluate the safety of administering rituximab at a more rapid infusion rate in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to biopharmaceuticals that treat diseases by interfering with tumor necrosis factor (anti-TNF therapies), and were receiving methotrexate therapy for more than eight weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
351
1000 mg in 250 mL intravenous infusion
10 to 25 mg/week (oral or parenteral)
100 mg methylprednisolone administered by slow intravenous infusion at least 30 minutes prior to the start of each study drug infusion
Percentage of Participants Experiencing Any Infusion-related Reaction (IRR) Associated With the Second Rituximab Infusion
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
Percentage of Participants Experiencing Any Serious IRR (SIRR) Associated With the Second Rituximab Infusion
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
Percentage of Participants Experiencing Any IRR or SIRR Associated With the Third Rituximab Infusion
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
Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Second Rituximab Infusion
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.
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1 gram acetaminophen administered orally 30 to 60 minutes prior to the start of each study drug infusion
50 mg diphenhydramine hydrochloride or equivalent dose of alternate antihistamine administered orally 30 to 60 minutes prior to the start of each study drug infusion
Uni Of Alabama,Birmingham; Medicine - Rheumatology
Birmingham, Alabama, United States
Clnical & Translational Reseach Center for Alabama, PC
Tuscaloosa, Alabama, United States
ArthroCare, Arthritis Care; and Research P.C.
Gilbert, Arizona, United States
Valley Arthritis Care
Phoenix, Arizona, United States
Catalina Pointe Rheumatology
Tucson, Arizona, United States
Medvin Clinical Research
Covina, California, United States
Triwest Research Associates
La Mesa, California, United States
Medvin Clinical Research
Los Angeles, California, United States
Brigid Freyne-Private Practice; Internal Medicine, Rheum
Murrieta, California, United States
Desert Medical Advances; Rheumatology
Palm Desert, California, United States
...and 76 more locations
Time frame: Within 24 hours of beginning infusion on Day 15
Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Second Rituximab Infusion
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
Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Third Rituximab Infusion
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
Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Third Rituximab Infusion
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