A Phase II study of Rituximab ( Rituxan ) for relapsing-remitting multiple sclerosis ( RRMS ) met its primary endpoint. The study of 104 patients showed a statistically significant reduction in the total number of gadolinium enhancing T1 lesions observed on serial MRI scans of the brain at weeks 12, 16, 20 and 24 in the Rituxan-treated group compared to placebo.
Rates of overall adverse events and serious adverse events were comparable between the two treatment groups. Serious infectious adverse events occurring in Rituxan-treated patients included gastroenteritis and bronchitis. The overall rates of infection were comparable among the two treatment groups with an increase in the rates of nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis in the Rituxan-treated patients. There were more first infusion-related reactions with Rituxan, the majority of which were mild to moderate and were generally reversible with medical intervention.
This Phase II randomized, double-blind, parallel-group, placebo-controlled, multi-center study was designed to evaluate safety and efficacy of Rituxan in adults with relapsing-remitting multiple sclerosis.
A total of 104 patients at 48 sites in the U.S. and Canada were randomized to receive either a single treatment course of Rituxan or placebo.
Gadolinium-enhancing lesions visible by MRI scans were assessed at 12, 16, 20 and 24 weeks. Patients will continue to be followed for 48 weeks.
Multiple sclerosis is the leading cause of neurological disability in young adults. Neurological disability typically accumulates over time and includes muscle weakness and spasticity, balance and coordination problems, as well as memory impairment and depression. Other symptoms include numbness, pain, slurred speech and blurred vision. Many patients experience fatigue and problems with bladder, bowel or sexual function.
Relapsing-remitting multiple sclerosis is the most common form of multiple sclerosis and accounts for approximately 65 percent of all MS cases. RRMS is characterized by acute exacerbations with full or partial recovery between attacks. The disease does not progress between attacks.
The safety profile of Rituxan has been established in more than 960,000 patient exposures over a period of eight years.
In general, the adverse events observed in patients with rheumatoid arthritis, an autoimmune disease, were similar in type to those seen in patients with non-Hodgkin's lymphoma ( NHL ).
The most common adverse events observed in patients treated with Rituxan for rheumatoid arthritis in clinical trials were infusion reactions and infections.
No significant change in average immunoglobulin levels was observed in Rituxan-treated patients in clinical trials. There was no increase in hematologic malignancies, demyelinating events or risk of opportunistic infections ( including tuberculosis ) in Rituxan-treated patients over 24 weeks of treatment. Although 5 percent of Rituxan-treated patients developed human anti-chimeric antibodies ( HACA ), this was not associated with loss of clinical response or additional safety observations.
The majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like illness, fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema, hypotension and hypoxia. These symptoms vary in severity and generally are reversible with medical intervention.
Severe infusion reactions have been reported in patients treated with Rituxan, some with fatal outcomes in patients with NHL.
These severe reactions typically occur during the first infusion. The most severe manifestations and sequelae include pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid events. Patients who develop clinically significant infusion reactions should have their Rituxan infusion discontinued and receive medical treatment.
Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of tumor lysis syndrome following treatment with Rituxan.
Severe mucocutaneous skin reactions, some with fatal outcome, have been reported in association with Rituxan treatment. Patients experiencing a severe mucocutaneous reaction should not receive any further infusions and seek prompt medical evaluation. Abdominal pain, bowel obstruction and perforation, in some cases leading to death, were observed in patients receiving Rituxan in combination with chemotherapy for diffuse large B-cell ( DLBCL ), CD20-positive, non-Hodgkin's lymphoma.
Other serious or potentially life-threatening adverse reactions that have been reported following Rituxan therapy include Hepatitis B reactivation with fulminant hepatitis, other viral infections, hypersensitivity reactions, and cardiac arrhythmias.
Source: Genentech, 2006