Ritiximab (Rituxan) for Refractory Moderate to Severe Rheumatoid Arthritis
from Medscape Medical News
Rituximab (Rituxan) for Refractory Moderate to Severe Rheumatoid Arthritis
On February 28, the FDA approved a new indication for rituximab injection (Rituxan, made by Genentech, Inc, and Biogen Idec, Inc, and marketed as MabThera in Europe), allowing its use in combination with methotrexate to reduce signs and symptoms of moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response to one or more anti–tumor necrosis factor therapies.
According to a company news release, approximately one third of patients with RA do not respond to currently available biologic therapies. Rituximab is the first treatment of RA that selectively targets CD20-positive B-cells to provide lasting improvement in this subgroup of patients who are considered the most difficult to treat, with benefits observed after a single course of therapy.
The approval was based on a priority review of data from 3 randomized, double-blind, placebo-controlled trials in patients with active RA.
Results of the pivotal phase 3 (REFLEX) trial in 520 patients showed that the addition of a single treatment course of 2 rituximab infusions (1000 mg on days 1 and 15) to a stable dose of methotrexate yielded significant improvements in joint pain, inflammation, and physical function at 24 weeks compared with methotrexate alone, as determined using the American College of Rheumatology (ACR) 20, 50, and 70 response rates (51% vs 18%, 27% vs 5%, and 12% vs 1%, respectively).
The most commonly observed adverse events in rituximab-treated patients were infusion reactions and infections. Infusion reactions were serious in less than 1% of patients, and the incidence of serious infection was 2% (vs placebo, 1%). The overall rate of serious adverse events was 7% in patients treated with rituximab vs 10% of those administered placebo.
Rituximab therapy was not associated with a significant change in average immunoglobulin levels. No increases were observed in the risks for hematologic malignancies, demyelinating events, or opportunistic infections, including tuberculosis.
According to the news release, no long-term safety concerns were identified in more than 800 rituximab-treated patients followed up for 1 year or more.
It should be noted that severe and potentially fatal infusion reactions have been reported with use of rituximab in patients with non-Hodgkin lymphoma, typically occurring during the first infusion. Infusions should be discontinued and medical treatment administered to patients who develop clinically significant reactions.
Severe and potentially fatal mucocutaneous reactions have also been reported in rituximab-treated patients. Patients who experience such a reaction should be evaluated promptly; no further infusions should be administered.
Rituximab was approved previously for the treatment of relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. It is also indicated for the first-line treatment of diffuse large B-cell CD20-positive non-Hodgkin lymphoma, in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based chemotherapy regimens.
Its potential benefit as add-on therapy in patients with RA who have an inadequate response to methotrexate is currently being studied in a large pivotal phase 3 study consisting of 3 trials. Other potential indications include other immune diseases, including lupus and multiple sclerosis.
Rituximab (Rituxan) for Refractory Moderate to Severe Rheumatoid Arthritis
On February 28, the FDA approved a new indication for rituximab injection (Rituxan, made by Genentech, Inc, and Biogen Idec, Inc, and marketed as MabThera in Europe), allowing its use in combination with methotrexate to reduce signs and symptoms of moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response to one or more anti–tumor necrosis factor therapies.
According to a company news release, approximately one third of patients with RA do not respond to currently available biologic therapies. Rituximab is the first treatment of RA that selectively targets CD20-positive B-cells to provide lasting improvement in this subgroup of patients who are considered the most difficult to treat, with benefits observed after a single course of therapy.
The approval was based on a priority review of data from 3 randomized, double-blind, placebo-controlled trials in patients with active RA.
Results of the pivotal phase 3 (REFLEX) trial in 520 patients showed that the addition of a single treatment course of 2 rituximab infusions (1000 mg on days 1 and 15) to a stable dose of methotrexate yielded significant improvements in joint pain, inflammation, and physical function at 24 weeks compared with methotrexate alone, as determined using the American College of Rheumatology (ACR) 20, 50, and 70 response rates (51% vs 18%, 27% vs 5%, and 12% vs 1%, respectively).
The most commonly observed adverse events in rituximab-treated patients were infusion reactions and infections. Infusion reactions were serious in less than 1% of patients, and the incidence of serious infection was 2% (vs placebo, 1%). The overall rate of serious adverse events was 7% in patients treated with rituximab vs 10% of those administered placebo.
Rituximab therapy was not associated with a significant change in average immunoglobulin levels. No increases were observed in the risks for hematologic malignancies, demyelinating events, or opportunistic infections, including tuberculosis.
According to the news release, no long-term safety concerns were identified in more than 800 rituximab-treated patients followed up for 1 year or more.
It should be noted that severe and potentially fatal infusion reactions have been reported with use of rituximab in patients with non-Hodgkin lymphoma, typically occurring during the first infusion. Infusions should be discontinued and medical treatment administered to patients who develop clinically significant reactions.
Severe and potentially fatal mucocutaneous reactions have also been reported in rituximab-treated patients. Patients who experience such a reaction should be evaluated promptly; no further infusions should be administered.
Rituximab was approved previously for the treatment of relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. It is also indicated for the first-line treatment of diffuse large B-cell CD20-positive non-Hodgkin lymphoma, in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based chemotherapy regimens.
Its potential benefit as add-on therapy in patients with RA who have an inadequate response to methotrexate is currently being studied in a large pivotal phase 3 study consisting of 3 trials. Other potential indications include other immune diseases, including lupus and multiple sclerosis.
posted by Ricardo Pocurull at 7:34 AM
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