8 years of FDA approval with GPA and MPA

RITUXAN + GCC PROVEN TO ACHIEVE COMPLETE REMISSION FOR ADULT PATIENTS WITH GPA & MPA^[11]*

Induction treatment: In the RAVE Trial, 64% of patients induced with Rituxan and GCC achieved complete remission (BVAS/GPA^†=0 and 0 mg prednisone) at 6 months compared with 53% of patients treated with CYC followed by AZA, thereby demonstrating non-inferiority.^[11]
- Rituxan + GCC: Also proven to reduce major relapses
Follow-up treatment: In the MAINRITSAN study, 5% of patients treated with the rituximab regimen experienced a major relapse^‡ at 28 months vs 29% of patients treated with AZA + GCC^[13]

Rituximab regimen=Roche-manufactured, European Union–approved rituximab + GCC.

The BOXED WARNINGS for Rituxan include: Infusion Reactions, Severe Mucocutaneous Reactions, Hepatitis B Virus (HBV) Reactivation, and Progressive Multifocal Leukoencephalopathy (PML).

*Follow-up treatment with Rituxan may be used in patients who have achieved disease control with Rituxan, a rituximab product, or with other immunosuppressants.

Rituxan: a legacy of experience

Rituxan milestones from 2002 to today

Efficacy and Safety data

Review efficacy and safety data from the induction and follow-up treatment trials

Patient access

Get information and resources for patient financial support and programs

AZA, azathioprine; CYC, cyclophosphamide; GCC, glucocorticoids; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis.
^†The Birmingham Vasculitis Activity Score for Granulomatosis with Polyangiitis (BVAS/GPA). For new or worse disease ranges from 0 to 68, with higher scores indicating more active disease. A BVAS/GPA of 0 indicates remission.
^‡Major relapse was defined by the reappearance of clinical and/or laboratory signs of vasculitis activity (BVAS>0) that could lead to organ failure or damage, or could be life-threatening.

INDICATION

Rituxan^® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult and pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)

BOXED WARNINGS and Additional Important Safety Information

BOXED WARNINGS

Infusion-Related Reactions: Rituxan administration can result in serious, including fatal infusion-related reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Monitor patients closely. Discontinue Rituxan infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions.

Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with Rituxan, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with Rituxan. Discontinue Rituxan and concomitant medications in the event of HBV reactivation.

Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving Rituxan. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Warnings and Precautions

Tumor Lysis Syndrome (TLS): Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of Rituxan in patients with Non–Hodgkin’s Lymphoma (NHL). Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.

Infections: Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of Rituxan-based therapy. Discontinue Rituxan for serious infections and institute appropriate anti-infective therapy. Rituxan is not recommended for use in patients with severe, active infections.

Cardiovascular Adverse Reactions: 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.

Renal Toxicity: Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with Non–Hodgkin’s Lymphoma (NHL). Monitor closely for signs of renal failure and discontinue Rituxan in patients with a rising serum creatinine or oliguria.

Bowel Obstruction and Perforation: Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving Rituxan in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization: The safety of immunization with live viral vaccines following Rituxan therapy has not been studied, and vaccination with live vaccines is not recommended before or during treatment. For patients treated with Rituxan, physicians should review the patient’s vaccination status and patients should, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating Rituxan and administer non-live vaccines at least 4 weeks prior to a course of Rituxan.

Embryo-Fetal Toxicity: Rituxan can cause fetal harm due to B-cell lymphocytopenia in infants exposed to Rituxan in-utero. Advise pregnant women of the risk to a fetus. Females of childbearing potential should use effective contraception while receiving Rituxan and for 12 months following the last dose of Rituxan.

Concomitant Use With Biologic Agents and DMARDs Other Than Methotrexate: Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly. Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA or MPA patients exhibiting peripheral B-cell depletion following treatment with Rituxan.

Adverse Reactions

Clinical Trials Experience in GPA and MPA

Adverse reactions reported in ≥15% of Rituxan-treated patients were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, and infusion-related reactions.

Induction Treatment of Patients with Active GPA/MPA (GPA/MPA Study 1)
Infusion-Related Reactions: In GPA/MPA Study 1, 12% vs 11% (Rituxan-treated vs cyclophosphamide) of patients experienced at least one infusion-related reaction. Infusion-related reactions included cytokine release syndrome, flushing, throat irritation, and tremor. In the Rituxan group, the proportion of patients experiencing an infusion reaction was 12%, 5%, 4%, and 1% following the first, second, third, and fourth infusions, respectively. Patients were premedicated with antihistamine and acetaminophen before each Rituxan infusion and were on background oral corticosteroids, which may have mitigated or masked an infusion-related reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion-related reactions.

Infections: In GPA/MPA Study 1, 62% vs 47% (Rituxan-treated vs cyclophosphamide-treated, respectively) of patients experienced an infection by Month 6. The most common infections in the Rituxan group were upper respiratory tract infections, urinary tract infections, and herpes zoster. The incidence of serious infections was 11% vs 10% (Rituxan-treated vs cyclophosphamide, respectively), with rates of approximately 25 and 28 per 100 patient-years, respectively. The most common serious infection was pneumonia.

Hypogammaglobulinemia: Hypogammaglobulinemia (IgA, IgG, or IgM below the lower limit of normal) has been observed in patients with GPA and MPA treated with Rituxan in GPA/MPA Study 1. At 6 months, in the Rituxan group, 27%, 58%, and 51% of patients with normal immunoglobulin levels at baseline had low IgA, IgG, and IgM levels, respectively, compared to 25%, 50%, and 46% in cyclophosphamide group.

Immunogenicity

A total of 23/99 (23%) Rituxan-treated patients with GPA or MPA tested positive for anti-rituximab antibodies by 18 months in GPA/MPA Study 1. The clinical relevance of anti-rituximab antibody formation in Rituxan-treated patients is unclear.

Treatment of Patients with GPA/MPA who have Achieved Disease Control with Induction Treatment (GPA/MPA Study 2)
In GPA/MPA Study 2, the safety profile was consistent with the known safety profile of Rituxan in immunologic indications.

Infusion-Related Reactions: In GPA/MPA Study 2, 7/57 (12%) patients in the EU-approved rituximab arm reported infusion-related reactions. The incidence of IRR symptoms was highest during or after the first infusion (9%) and decreased with subsequent infusions (<4%). One patient had two serious IRRs, two IRRs led to a dose modification, and no IRRs were severe, fatal, or led to withdrawal from the study.

Infections: In GPA/MPA Study 2, 30/57 (53%) patients in the EU-approved rituximab arm and 33/58 (57%) in the azathioprine arm reported infections. The incidence of all grade infections was similar between the arms. The incidence of serious infections was similar in both arms (12%). The most commonly reported serious infection in the group was mild or moderate bronchitis.

Treatment of Pediatric Patients with GPA/MPA (GPA/MPA Study 4)
The safety profile in pediatric GPA and MPA patients was consistent in type, nature and severity with the known safety profile of Rituxan in adult patients with FDA-approved immunological indications.

Infusion-Related Reactions
In GPA/MPA Study 4, the proportion of patients experiencing an IRR was 32%, 20%, 12%, and 8% following the first, second, third, and fourth infusions, respectively. The observed symptoms of IRRs were similar to those in adult GPA and MPA patients treated with Rituxan.

Serious Infections
Serious infections were reported in 7 patients (28%), and included influenza (2 patients [8%]) and lower respiratory tract infection (2 patients [8%]) as the most frequently reported events.

Hypogammaglobulinemia
Hypogammaglobulinemia (IgG or IgM below the lower limit of normal), including prolonged hypogammaglobulinemia (defined as Ig levels below lower limit of normal for at least 4 months) was observed in GPA/MPA Study 4. During the overall study period, 18/25 patients (72%) had prolonged low IgG levels, including 15 patients who also had prolonged low IgM. Three patients received treatment with intravenous immunoglobulin.

You may report side effects to the FDA at (800) FDA‑1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional Important Safety Information, please see the Rituxan full Prescribing Information, including BOXED WARNINGS.

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