Rituxan Clinical Data
- In the REFLEX pivotal trial, a significantly higher proportion of patients treated with one course of Rituxan achieved an ACR response vs placebo
- ACR 20, 50, and 70 responses at 6 months for the Rituxan + MTX group (n=298) and the placebo + MTX group (n=201) were, respectively: 51% vs 18%, 27% vs 5%, 12% vs 1%
Pivotal radiographic data at 2 years in TNFi IR patients
Baseline demographics and disease characteristics1,2
![Serious infection[1]](/ra/hcp/images/about/baseline-demo-char.gif)
A total of 520 patients were enrolled in the study. 311 were randomized to Rituxan plus MTX and 209 to placebo plus MTX; 3 patients were randomized but did not receive treatment. 468 patients (281 Rituxan patients and 187 placebo patients) were included in the REFLEX ITT population, and had a baseline film at screening and at least one postbaseline radiograph. A total of 197 Rituxan and 135 placebo patients had radiographs at both baseline and Week 104. The baseline characteristics and measures of disease activity were similar in both treatment groups and were similar to those of the original ITT population.1,2
Rituxan protects joints by slowing the progression of structural damage1
![Serious infection[1]](/ra/hcp/images/about/radiographic-changes.gif)
A total of 520 patients were enrolled in the study. 311 were randomized to rituximab plus MTX and 209 to placebo plus MTX; 3 patients were randomized but did not receive treatment. 468 patients (281 rituximab patients and 187 placebo patients) were included in the REFLEX ITT population, and had a baseline film at screening and at least one post baseline radiograph. A total of 197 rituximab and 135 placebo patients had radiographs at both baseline and Week 104. The baseline characteristics and measures of disease activity were similar in both treatment groups and were similar to those of the original ITT population.1
Adapted from Cohen et al 2010.
At 2 years, 82% of the placebo population had received at least 1 course of Rituxan.1
- Patients enrolled in the REFLEX Trial were eligible for rescue therapy with active drug at 4 months1
IMPORTANT SAFETY INFORMATION
Cardiovascular:
- Discontinue infusions for serious or life-threatening cardiac arrhythmias
- Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina
Cardiac Adverse Reactions
- In the pooled, placebo-controlled studies, the proportion of patients with serious cardiovascular reactions was 1.7% and 1.3% in Rituxan and placebo treatment groups, respectively
- Three cardiovascular deaths occurred during the double-blind period of the RA studies including all Rituxan regimens (3/769 = 0.4%) as compared to none in the placebo treatment group (0/389)
- In the experience with Rituxan in 2578 RA patients, the rate of serious cardiac reactions was 1.93 per 100 patient years
- The rate of myocardial infarction (MI) was 0.56 per 100 patient years (28 events in 26 patients), which is consistent with MI rates in the general RA population. These rates did not increase over three courses of Rituxan
- Since patients with RA are at increased risk for cardiovascular events compared with the general population, patients with RA should be monitored throughout the infusion and Rituxan should be discontinued in the event of a serious or life-threatening cardiac event
REFERENCES
- 1.
- Cohen SB, Keystone E, Genovese MC, et al. Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate. Ann Rheum Dis. 2010;69(6):1158-1161.
- 2.
- Data on file, Genentech USA/Biogen Idec.
Radiographic Data at 5 Years in Open-label Extension
Care should be taken when interpreting these data, as they constitute the results of a study based on open-label data.
Trial Design1
In the 5-year REFLEX open-label extension trial, patients with an inadequate response to TNFis received background MTX and were randomized initially to Rituxan or placebo1
- Rituxan is administered as two-1000 mg intravenous infusions separated by 2 weeks. Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks
Among the 79 placebo→Rituxan patients at Year 5, 71 were rescued with Rituxan within the first year.1
A total of 520 patients were enrolled in the study. 311 were initially randomized to Rituxan plus MTX and 209 to placebo plus MTX. Patients initially randomized to placebo plus MTX were eligible for rescue therapy with Rituxan at 4 months. After 6 months, 480 patients (308 Rituxan patients and 172 placebo patients) were subsequently transferred to the open-label extension in which all patients were eligible to be transferred to Rituxan. At Year 5, 139 of the Rituxan patients and 102 of the placebo→Rituxan patients remained in the study; 105 of the Rituxan patients and 79 of the placebo→Rituxan patients had radiographs available at baseline and Year 5.
Dosing intervals were based on physician's clinical judgment, no sooner than 16 weeks.1
Adapted from Keystone ACR 2011.
Baseline Demographics and disease characteristics across groups1
Baseline demographics and disease characteristics were generally balanced between the groups, with the exception of RA disease duration which was slightly longer in the Rituxan group (13.5 years) versus the placebo→Rituxan group (10.5 years).1
Both groups were exposed to a similar number of courses of Rituxan over the 5 years: Rituxan: mean (standard deviation [SD]), 5.1 (2.1); median (range), 5 (1-12) placebo→Rituxan: mean (SD), 5.0 (2.3); median (range), 5 (0-12).1
Data are mean (standard deviation), unless stated.
aPLB→Rituxan, n=78.
CRP, C-reactive protein; DAS28, Disease Activity Score in 28 joints; ESR, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; RA, rheumatoid arthritis; SJC, swollen joint count; TJC, tender joint count.
IMPORTANT SAFETY INFORMATION
Cardiovascular:
- Discontinue infusions for serious or life-threatening cardiac arrhythmias
- Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina
Care should be taken when interpreting these data, as they constitute the results of a study based on open-label data.
- At 2 years, patients originally randomized to Rituxan demonstrated significantly slower progression of joint damage compared to patients originally randomized to placebo
- Joint damage was measured by total Genant-modified Sharp, erosion and joint space narrowing scores
Radiographic changes over time
- At 2 years, patients originally randomized to Rituxan demonstrated significantly slower progression of joint damage compared to patients originally randomized to placebo
- Joint damage was measured by total Genant-modified Sharp, erosion and joint space narrowing scores
Care should be taken when interpreting these data, as the constitute the results of a study based on open-label data.
Patients originally randomized to Rituxan were observed to have slower progression of joint damage over 5 years compared with patients originally randomized to placebo.1
IMPORTANT SAFETY INFORMATION
CARDIOVASCULAR:
- Discontinue infusions for serious or life-threatning cardiac arrhythmias
- Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina
REFERENCE
- 1.
- Keystone E, Cohen SB, Emery P, et al. Sustained inhibition of structural damage in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitors prior to rituximab treatment: 5-year data from the REFLEX study. Presented at: The American College of Rheumatology Annual Scientific Meeting; November 5-9, 2011, Chicago, IL. Poster 2208.
