Rituxan in clinical trials Print Page

The efficacy and safety of Rituxan have been demonstrated in 8 clinical and 2 extension trials to date. To learn more about the design and findings of specific trials, please select from the list below.

• REFLEX (Study 1 in Rituxan Prescribing Information)
• REFLEX: 2 year joint protection data (A subanalysis of Study 1 in Rituxan Prescribing Information)
• 6-year pooled safety analysis
• SUNRISE
• 4-Course pooled efficacy analysis
• SIERRA
• SERENE (Study 4 in Rituxan Prescribing Information)
• Safety of biologics post-Rituxan

REFLEX (Study 1 in Rituxan Prescribing Information): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating Primary Efficacy and Safety at 24 Weeks

Objective

• To determine the efficacy and safety of treatment with rituximab plus methotrexate in patients with active RA who had an inadequate response to prior TNFi therapies
• To explore the pharmacokinetics and pharmacodynamics of rituximab in this population

Design

• Phase 3 randomized, double-blind, placebo-controlled ITT analysis
• Primary efficacy and safety were evaluated at 24 weeks
• After 24 weeks, patients entered a post-treatment period and had follow-up evaluations every 2 months for 18 months, for an overall study duration of 24 months

Patient Groups

• N=520
• Patients were randomized at a ratio of 3:2 to receive IV infusions of rituximab or placebo on Days 1 and 15
• Both groups continued to take stable doses of methotrexate

End Points

• The primary end point was the proportion of patients with an ACR 20 response at Week 24
• Secondary end points included ACR 50 and ACR 70 responses, changes from baseline to Week 24 in DAS28 score, EULAR response criteria, and the individual parameters of the ACR improvement criteria
• Additional end points included changes from baseline to Week 24 in the FACIT-F score, the SF-36, and the Genant-modified Sharp radiographic score u

Source: Cohen SB, Emery P, Greenwald MW, et al; for the REFLEX Trial Group. Arthritis Rheum. 2006;54(9):2793-2806.

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REFLEX 2-Year JP (A subanalysis of Study 1 in Rituxan Prescribing Information): Continued Inhibition of Structural Damage in RA Patients Treated With Rituximab at 2 Years

Objective

• To determine whether inhibition of structural damage is maintained through 2 years of treatment

Design

• Patients drawn from REFLEX study
• Analyzed according to the ITT principle

Patient Groups

• Baseline and post-baseline (24 or 56 week) X-ray and Week 104 X-ray
• Patients must have baseline and at least 1 post-baseline X-ray
• Radiographs taken at 24, 56, and 104 weeks
• Linear extrapolation used for patients missing Week 104 data

End Points

• Primary radiographic end point: Mean change at 2 years vs baseline in Genant-modified Sharp score
• Secondary radiographic end points included erosion score, joint-space–narrowing score, and proportion of patients with no further joint progression

Source: Cohen S, Keystone E, Genovese MC, et al. Poster presented at ACR 2008.

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Long-term safety of Patients Receiving Rituximab in RA Clinical Trials

Objective

• To evaluate the long-term safety of rituximab in patients with RA in clinical trials

Design

• Pooled analysis of safety data, including adverse events and infections, from patients treated with rituximab plus methotrexate in global clinical trials

Patient Groups

• Patients received rituximab or placebo in original study, followed by rituximab as rescue therapy or part of open-label extension study
• The placebo population comprised all patients who received a placebo infusion who either did not or had not yet received rituximab, together with data from patients who received placebo and were subsequently exposed to rituximab
• Patients were drawn from the following studies: REFLEX, SERENE, SUNRISE, MIRROR, SIERRA, DANCER, Edwards (IIa), and the DANCER/IIa and REFLEX extensions

End Points

• Data were collected on overall and serious adverse events, infusion-related reactions, immunogenicity, infections and serious infections, immunoglobulin levels, cardiovascular events, and malignancies

Source: van Vollenhoven RF, Emery P, Bingham CO III, et al. Presented at ACR 2009.

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SUNRISE: Efficacy and Safety of Retreatment With Rituximab in RA: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial

Objective

• To evaluate efficacy and safety of retreatment in patients with active RA who had had inadequate response to 1 or more TNFi therapies

Design

• Phase 3 randomized, double-blind, placebo-controlled ITT analysis

Patient Groups

• N=559
• All enrolled patients received open-label rituximab 2 x 1000 mg on Days 1 and 15
• All patients received concurrent methotrexate
• Between Weeks 24 and 40, patients not in DAS remission were randomized 2:1 to receive an additional course of rituximab 2 x 1000 mg (n=318) or placebo (n=157)
• Baseline characteristics and disease activity were comparable for rituximab and placebo populations
• 291 rituximab and 134 placebo patients completed 48 weeks

End Points

• Primary end point: Proportion of retreated patients achieving ACR 20 response at Week 48 compared with baseline
• Secondary end points included ACR 50 and ACR 70, changes in DAS28 and EULAR response at 48 weeks compared with baseline, and changes in ACR core set parameters

Source: Mease P, Cohen S, Gaylis N, et al. J Rheumatol. In press.

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Multiple Courses of Rituximab Produce Sustained Efficacy in TNF-IR Patients With RA

Objective

• To assess the effect of repeat courses of rituximab in TNF-IR RA patients responding to their first and second course

Design

• Pooled completer analysis of TNF-IR patients from clinical trials and open-label extensions of REFLEX, DANCER, Keystone, Edwards, MIRROR, SIERRA, and SUNRISE who responded to an initial course of therapy

Patient Groups

• Depending on the study, patients received retreatment at either 6-month intervals or as needed according to physician evaluation
• 1324 TNF-IR received at least one course
• 146 TNF-IR received at least four courses

End Points

• All ACR, EULAR, HAQ, and DAS28 responses, together with mean changes, were calculated from the first treatment course baseline
• Efficacy data by course were presented as both “as observed” and "within patient, within visit"
• All presented data were observed, with no imputation methods applied

Source: Keystone E, Fleishmann RM, Emery P, et al. Poster presented at ACR 2009.

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SIERRA: Immunization Responses in RA Patients Treated With Rituximab

Objective

• To evaluate recall response to protein antigens in RA patients receiving rituximab plus methotrexate compared with those receiving methotrexate alone

Design

• A multicenter study in patients with active RA receiving a stable dose of methotrexate

Patient Groups

• N=103
• Patients were stratified by age and randomized 2:1 to receive rituximab (1000 mg IV x 2, 2 weeks apart) plus methotrexate for 36 weeks (Active group) vs continuing methotrexate alone for 12 weeks (Control group)
• Patients in both groups received tetanus toxoid adsorbed vaccine (Active: Week 24; Control: Day 1), 23-valent pneumococcal polysaccharide vaccine (23VPPV, Active: Week 28; Control: Week 4), neoantigen keyhole limpet hemocyanin (KLH, Active: Weeks 32, 33; Control: Weeks 8,9), and Candida albicans skin test (Active: Day 1, Week 24; Control: Day 1, Week 12)

End Points

• Anti-tetanus, anti-pneumococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration
• Delayed-type hypersensitivity (DTH) skin test response was measured 2 to 3 days following placement
• Primary outcome was the proportion of patients with at least a fourfold rise in anti-tetanus IgG
• Secondary outcome measures were responses to both 23VPPV and KLH, and maintenance of DTH responses to the C albicans skin test

Source: Bingham C, Looney RJ, Deodhar A, et al. Arthritis Rheum. In press.

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SERENE (Study 4 in Rituxan Prescribing Information): Efficacy and Safety of Rituximab as First-Line Biologic Therapy in Patients With Active RA

Objective

• To evaluate efficacy and safety of rituximab plus methotrexate compared with methotrexate monotherapy in patients with active RA who had an inadequate response to methotrexate and are naive to prior biologic therapy

Design

• Phase 3 randomized, placebo-controlled to 24 weeks
• Remained double-blinded to treatment arm and dose through Week 48

Patient Groups

• N=512
• Randomized in 1:1:1 fashion to receive rituximab 2 × 500 mg, rituximab 2 × 1000 mg, or placebo on Days 1 and 15
• All patients received concurrent methotrexate
• After minimum of 24 weeks, eligible patients retreated with rituximab
• Eligible placebo-treated patients received rituximab 2 x 500 mg at 24 weeks
• Eligible patients initially treated with rituximab retreated with their original dose
• DAS ≥2.6 required to qualify for retreatment

End Points

• Primary end point: Proportion of patients achieving ACR 20 at Week 24
• Secondary end points included proportion achieving ACR 50 and ACR 70, changes in DAS28, and EULAR response at Week 24
• Exploratory end points included ACR 20/50/70 responses over time

Source: Emery P, Rigby WF, Latinis K, et al; for the SERENE Study Group. Poster presented at ACR 2009.

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Safety of Biologic Therapies Following Rituximab Treatment in RA Patients

Objective

• To describe the rate of serious infection events in RA patients treated with rituximab and subsequently receiving a biologic DMARD

Design

• Following withdrawal from respective studies, patients entered a safety follow-up (SFU) period during which peripheral B-cell levels were regularly monitored
• Patients could receive additional biologics. Data on serious infection events, B-cell levels, and concomitant medications were collected throughout the SFU

Patient Groups

• RA patients who had received more than one course of rituximab and withdrew from the treatment phase of an international RTX clinical trial
• Patients were drawn from the following studies: REFLEX, SERENE, SUNRISE, MIRROR, SIERRA, DANCER, Edwards (IIa), and the DANCER/IIa and REFLEX extensions

End Points

• Serious infection events were collected for all patients receiving a biologic DMARD, before and after treatment
• Serious infection events were analyzed for all patients receiving a subsequent TNFi, before and after treatment

Source: Genovese MC, Breedveld FC, Emery P. Ann Rheum Dis. Published online January 20, 2009; doi:10.1136/ard.2008.101675.

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