Rituxan (Rituximab)

Rituximab (Rituxan) is a monoclonal antibody targeting the protein CD20 that occurs on the surface of B-cells, a type of lymphocyte that plays a key role in immune response. It is manufactured by Genentech and Biogen Idec. Rituxan is indicated (approved for use) for the treatment of RA in combination with methotrexate in adult patients with moderately- to severely-active RA who have had an inadequate response to one or more anti-TNF treatments. Rituxan is also indicated for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and granulomatosis with polyangiitis (a rare disease that involves inflammation of blood vessels and affects the lungs, kidneys, and sinuses).

 

Rituximab (Rituxan): overview and efficacy

Rituximab (Rituxan) is a monoclonal antibody targeting the protein CD20 that occurs on the surface of B-cells, a type of lymphocyte that plays a key role in immune response. It is manufactured by Genentech and Biogen Idec. Rituxan is indicated (approved for use) for the treatment of RA in combination with methotrexate in adult patients with moderately- to severely-active RA who have had an inadequate response to one or more anti-TNF treatments. Rituxan is also indicated for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and granulomatosis with polyangiitis (a rare disease that involves inflammation of blood vessels and affects the lungs, kidneys, and sinuses).1

 

How is Rituxan taken?

Rituxan is given in combination with methotrexate as two intravenous (IV) infusions of 1000 mg each separated by 2 weeks (this is considered one course of treatment). Courses of Rituxan are given every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Premedication with methylprednisolone 100 mg IV, or equivalent glucocorticoid, and benadryl is recommended 30 minutes before each infusion.1 An infusion of Rituxan may take 4-6 hours.

 

How does Rituxan work?

Rituximab (Rituxan) is an antibody that targets the protein CD20 that occurs on the surface of mature B-cells, which play a key role in immune response. Remember that our bodies naturally produce antibodies against bacteria, viruses, and other foreign organisms that invade and pose a threat to our bodies. Following the example of our bodies, drug makers have engineered different antibodies designed to target the mechanisms that cause a variety of diseases, including RA. CD20 plays an important role in helping B cells function in the immune response, so inhibiting CD20 depletes mature B-cells and limits their ability to promote inflammation.1

 

Are there people who should not take Rituxan?

There is an increased risk for serious infections with Rituxan. This is because Rituxan can decrease the ability of the immune system to fight infections. Rituxan should not be taken by a patient with an active infection and should be stopped until the infection is resolved. There is a risk of reactivation of hepatitis B virus (HBV) infection with Rituxan. Therefore, carriers of the virus should be monitored while taking Rituxan and for several months after treatment.1

Patients at risk for cardiac arrhythmias and angina should be monitored carefully during treatment with Rituxan.1
Rituxan is a pregnancy category C drug. While there have been no well-controlled studies in humans, post-marketing data showed that infants exposed to Rituxan in utero developed B-cell lymphocytopenia (a decrease in levels of white blood cells) lasting less than 6 months. Rituxan should only be used in pregnant women if the potential benefits justify the risk to the fetus.1

It is unknown whether Rituxan is excreted into human milk. Because of the potential for adverse effects to the nursing infant, the unknown risks of exposure to Rituxan should be weighed against the benefits of breastfeeding.1

 

What evidence do we have that Rituxan works in RA?

The effectiveness of Rituxan in RA has been studied in two randomized, controlled trials in adult patients with moderately- to severely-active RA.

In Study 1, patients were randomized to 2 doses of Rituxan 1000 mg + methotrexate or placebo + methotrexate for a period of 24 weeks. The blinded portion of the study was followed by an open-label extension in which further courses of Rituxan were given.

In Study 2, all patients received an initial course of Rituxan (two doses of 1000 mg) + methotrexate. Those who continued to experience active RA were randomized to either a second course of Rituxan + methotrexate or placebo + methotrexate.1

A third randomized, controlled study (Study 3) was conducted in patients with moderately- to severely-active RA who had never taken methotrexate. The study evaluated two different courses of Rituxan, randomizing patients to two doses of Rituxan 500 mg + methotrexate, two doses of Rituxan 1000 mg + methotrexate, and placebo + methotrexate.1
Disease activity and response. In Study 1, both the Rituxan and placebo treatment groups received a short course of IV and oral glucocorticoids, resulting in similar anti-inflammatory benefits at week 4. However, the Rituxan group had higher rates of ACR20 response at week 8 versus the placebo group and these were maintained through week 24 with the single course of Rituxan. A similar pattern of ACR50 and 70 responses occurred for the Rituxan group versus the placebo group.1

In Study 3, at 1 year ACR20, 50, and 70 responses were similar in the two Rituxan treatment groups and higher when compared with the placebo group.1

 

Rates of ACR responses from two clinical trials of Rituxan

Study 1

24-week placebo-controlled

Study 2

Placebo-controlled retreatment

Response Rituxan + MTX (N=298) Placebo + MTX (N=201) Treatment advantage Rituxan vs placebo Rituxan + MTX (N=318) Placebo + MTX (N=157) Treatment advantage Rituxan vs placebo
ACR20
Week 24 51% 18% 33% 45% 48% None
Week 48 54% 45% 11%
AC50
Week 24 27% 5% 21% 21% 27% None
Week 48 29% 26% 4%
ACR70
Week 24 12% 1% 11% 8% 11% None
Week 48 14% 13% 1%

 

Radiographic progression. In Study 1, x-rays were taken and scored using the Genant-modified Total Sharp Score to evaluate the progression of structural damage. Rituxan + methotrexate resulted in a greater slowing of the progression of structural damage than placebo + methotrexate at 1 year. In the open-label extension that followed the blinded phase of the study, there was a further decrease in progression of structural damage in patients who received Rituxan + methotrexate. In Study 3, the lower dose of Rituxan (two doses of 500 mg) had less efficacy versus the higher dose in terms of slowing radiographic progression.1

 

Radiographic change from baseline to 104 weeks in Study 1

Mean scores Rituxan 2 x 1000 mg + MTX Placebo + MTX
Change during year 1
Total Sharp-Genant Score 0.66 1.77
Erosion score 0.44 1.19
Joint space narrowing score 0.22 0.58
Change during year 2
Total Sharp-Genant Score 0.48 1.04
Erosion score 0.28 0.62
Joint space narrowing score 0.20 0.42

 

Is there a generic form of Rituxan?

There is no generic equivalent to Rituxan available at this time.

Written by: Jonathan Simmons | Last reviewed: September 2013.
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