/ Media / Product Information

Rituxan® (Rituximab) for Rheumatoid Arthritis (RA)

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.

People with serious infections should not receive Rituxan.

WARNINGS
Rituxan can cause serious side effects that can lead to death, including:

Infusion Reactions: Serious infusion reactions can happen during the infusion or within 24 hours of receiving Rituxan. Patients must tell their doctor or get medical help right away if they get any of these symptoms: hives (itchy red welts) or rash, itching, swelling of the lips, tongue, throat, or face, sudden cough, shortness of breath, difficulty breathing or wheezing, weakness, dizziness or feel faint, palpitations (feel like your heart is racing or fluttering) chest pain.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus. People with a weakened immune system can get PML. PML can result in death or severe disability. Patients must tell their doctor right away if they have any of the following symptoms: confusion or problems thinking, loss of balance, change in the way they walk or talk, decreased strength or weakness on one side of their body, blurred vision or loss of vision.
Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells and can occur after treatment with Rituxan. TLS can cause a person to have kidney failure and the need for dialysis treatment. TLS may also cause abnormal heart rhythm.
Severe Skin and Mouth Reactions: Patients may get painful sores on the skin or in the mouth, ulcers, blisters, or peeling skin while receiving or after receiving Rituxan.

Mechanism of Action

Rituxan represents an entirely new approach to treating RA. It is the first RA treatment that targets immune cells called B-cells, which originate from stem cells in the bone marrow. B-cells may play multiple roles in the initiation and development of RA including:

Presentation of antigens (substances capable of triggering an immune response), which may contribute significantly to T-cell responses.
Production of antibodies that trigger an immune attack against a person's own cells or tissues (autoantibodies) and perpetuate the disease process.
Production of chemical signal molecules (cytokines) known to promote inflammation and joint damage.

Rituxan binds to a specific protein (the CD20 marker on the surface of the cell) that is found on the surface of some B-cells. From there, Rituxan works with the immune system to selectively deplete CD20-positive B cells. Through this unique mechanism of action, Rituxan may affect three pathways by which B-cells are believed to contribute to the initiation and development of RA.

Rituxan does not target stem cells (B-cell progenitors) in the bone marrow, which lack the CD20 marker on the surface of the cells. Thus, B-cells can regenerate and gradually return to normal levels after treatment with Rituxan. Rituxan also does not target plasma cells.

Clinical Trial Results

In clinical trials for RA, Rituxan demonstrated significant improvement in RA signs and symptoms, with an extended duration of effect through six months from a single treatment course in adult RA patients who had an inadequate response to one or more TNF antagonist therapies.

The FDA approval of Rituxan for RA was based on data from three randomized, double-blind, placebo-controlled studies. Following is a summary of the results of the pivotal Phase III REFLEX study, which included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more tumor necrosis factor (TNF) antagonist therapies.

ACR Responses: A significantly greater proportion of patients who received a single treatment course of two infusions of Rituxan (1000 mg on days one and 15) with a stable dose of MTX displayed clinically and statistically significant improvements in RA signs and symptoms, including pain and disability, after 24 weeks. In patients receiving Rituxan:

51 percent achieved ACR 20, the primary endpoint of the study, versus 18 percent of placebo patients (p<0.0001)

27 percent achieved ACR 50, versus 5 percent of placebo patients (p<0.0001)

12 percent achieved ACR 70, versus 1 percent of placebo patients (p<0.0001)

ACR responses indicate a 20, 50 and 70 percent improvement in the number of swollen and tender joints, respectively, as well as a 20, 50 and 70 percent improvement compared with baseline in three of five disease-activity measures: patient global assessment, physician global assessment, assessment of pain, Health Assessment Questionnaire and the value for one acute phase reactant (erythrocyte sedimentation rate or C-reactive protein, markers of inflammation).

Approved Indications

Rituxan (Rituximab) received U.S. Food and Drug Administration approval in November 1997 for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (NHL).
In April 2001, a supplemental Biologics License Application was approved for Rituxan for these additional uses: retreatment of patients with Rituxan who have relapsed following initial Rituxan therapy, use of eight weekly doses (compared to original four) per course of treatment, treatment of patients with bulky disease (lesions > 10 cm).
In February 2006, the FDA approved Rituxan for the first-line treatment of diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma (DLBCL- a type of NHL) in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens.
Also in February 2006, the FDA approved Rituxan in combination with methotrexate for the treatment of moderately- to severely-active rheumatoid arthritis in patients who have had an inadequate response to one or more TNF antagonist therapies.
Additionally, in February 2010 Rituxan was approved in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL).

People with serious infections should not receive Rituxan.

Important Safety Information and Serious Side Effects

Rituxan can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (TLS; kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (PML; a rare, serious brain infection).

Infusion Reactions: Serious infusion reactions can happen during the infusion or within 24 hours of receiving Rituxan. The doctor should give the patient medicines before their infusion of Rituxan to decrease the chance of having a severe infusion reaction. If a serious reaction occurs, the infusion may be stopped and the patient should receive medical care. Patients must tell their doctor or get medical help right away if they get any of these symptoms: hives or rash, itching, swelling of the lips, tongue, throat, or face, sudden cough, shortness of breath, difficulty breathing or wheezing, weakness, dizziness or feel faint, palpitations, or chest pain.
Tumor Lysis Sydrome (TLS): TLS is caused by the fast breakdown of cancer cells and can occur after treatment with Rituxan. TLS can cause a person to have kidney failure and the need for dialysis treatment. TLS may also cause abnormal heart rhythm. The doctor may give the patient medicines to help prevent TLS and do blood tests to check the patient for TLS.
Severe Skin and Mouth Reactions: Severe skin and mouth reactions can occur in patients who receive Rituxan.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus. People with a weakened immune system can get PML. Patients must tell their doctor right away if they have any of the following symptoms: confusion or problems thinking, loss of balance, change in the way they walk or talk, decreased strength or weakness on one side of their body, blurred vision or loss of vision.
Rituxan has also been associated with serious and life-threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel that can sometimes lead to death.
The most common side effects of Rituxan in patients with non-Hodgkin's lymphoma (NHL) include: infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common serious side effect in NHL patients was low white blood cells.
The most common side effects of Rituxan in patients with chronic lymphocytic leukemia (CLL) were infusion reactions and low white blood cells.
Most CLL patients treated with Rituxan plus FC chemotherapy had at least one serious side effect. In clinical trials, CLL patients 70 years or older who received Rituxan with FC chemotherapy were more likely to experience severe side effects compared with younger patients who received the same treatment.
Patients should tell their doctor about any side effects that bothers them or that does not go away. These are not all of the possible side effects with Rituxan.

Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide at www.rituxan.com.

Dosing

In patients with RA, Rituxan is given as two-1000 mg IV infusions separated by two weeks. Glucocorticoids administered as methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions. The safety and efficacy of retreatment have not been established in controlled trials.

Rituxan is given in combination with methotrexate.

Additional Rituxan Information

Rituxan, discovered by Biogen Idec, is co-marketed by Genentech, Inc. and Biogen Idec in the United States and Roche markets MabThera® in the rest of the world, except Japan, where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. Rituxan has become the most widely studied and prescribed monoclonal antibody in the world.

Rituxan is also being studied in other autoimmune diseases with significant unmet medical needs, including systemic lupus erythematosus, lupus nephritis, multiple sclerosis and ANCA-associated vasculitis.

For a copy of the Rituxan full prescribing information, including Boxed Warning, please call (800) 821-8590 or visit http://www.rituxan.com.