The RITUXAN for RA EXPERIENCE Program

 

through Genentech
Rheumatology
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$4,000 per
12-month period
toward the cost of
Rituxan for eligible patients

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Indication

Rituxan® (rituximab) in combination with methotrexate is indicated for the treatment of adult patients with moderately to severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Rituxan is not recommended for treatment of patients with severe active infections.

Important Safety Information

RITUXAN administration can result in serious, including fatal, adverse reactions. These include: infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML).

Warnings and Precautions

Rituxan administration can also result in additional serious, including fatal, adverse reactions including:

  • hepatitis B reactivation
  • other infections including bacterial, fungal, new or reactivated viral infections
  • cardiovascular events

Patients should be closely observed for signs of infection if biologic agents and /or DMARDs other than methotrexate are used concomitantly

Common adverse reactions include infusion reactions and infections

For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.

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Rituxan in clinical trials

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): 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 posttreatment 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

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 postbaseline (24 or 56 week) X-ray and Week 104 X-ray
  • Patients must have baseline and at least 1 postbaseline 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

Care should be exercised in interpreting open-label results due to the inability to minimize bias

Source: van Vollenhoven RF, Emery P, Bingham CO III, et al. Presented at EULAR 2010.

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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. March 1, 2010; doi:10:3899/jrheum.090442.

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

Objective
  • To assess the effect of repeat courses of rituximab in TNFi-IR RA patients responding to their first and second course
Design
  • Pooled completer analysis of TNFi-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 TNFi-IR received at least one course
  • 146 TNFi-IR received at least 4 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

Care should be exercised in interpreting open-label results due to the inability to minimize bias

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 Candida albicans skin test

The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live vaccines is not recommended in patients receiving Rituxan. Follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of Rituxan.

Source: Bingham C III, Looney RJ, Deodhar A, et al. Arthritis Rheum. 2010;62(1):64-74.

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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 rituximab 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

Limited data are available on the safety of the use of biologic agents or
DMARDs other than methotrexate in patients exhibiting peripheral B-cell depletion following treatment with rituximab. Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly.

Source: Genovese MC, Breedveld FC, Emery P. Presented at EULAR 2010

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