Experimental Medications: Monoclonal Antibodies
- Given via IV infusion
- Being studied in RMS
Rituxan is a monoclonal antibody that binds to a receptor on the surface of B cells. These cells are then destroyed, and their levels in the circulation are decreased. It is approved for use in the treatment of lymphomas, leukemias, and autoimmune disorders.
Serious adverse events have been reported in Rituxan-treated patients with other diseases, including rare cases of progressive multifocal leukoencephalopathy (PML), the same viral infection of the brain that has been seen with a small percentage of patients taking some approved DMTs. While no PML has been diagnosed in MS patients taking Rituxan, the number of individuals with MS treated with Rituxan is relatively small to date.
New data from the University of Colorado assessed the safety profile and effectiveness of Rituxan in patients with MS. Researchers at the university’s Rocky Mountain MS Center followed 125 individuals with either relapsingremitting, primary-progressive, or secondaryprogressive MS. The mean follow-up period was 40.6 months, and participants received an average of six infusions or 4,954 mg of Rituxan.
Rituxan was found to be effective overall, with just 32 of the 125 participants experiencing a clinical relapse, enhancing lesion, or T2 lesion during the follow-up period. Infections occurred in 34 of the participants and resulted in either emergency room or hospital treatment. Sixty people suffered a mild-to moderate infusion reaction during the first or second infusion; 57 individuals had abnormally low counts of the IgM or IgG antibodies, and nine of the participants had a deficit of certain white blood cells. Two people were diagnosed with malignant cancer after they started Rituxan, but it is unclear whether the drug was a factor.49
Meanwhile, a review of Kaiser Permanente and Swedish data found that all-cause death rates among people with MS receiving Rituxan are lower compared with those of MS patients receiving other disease-modifying therapies. The researchers analyzed data on 1,246 individuals with MS from a Kaiser Permanente Southern California database, and 1,252 patients from a chart-validated subset of a Swedish MS registry. Most of these individuals had received initial Rituxan infusions of 1,000 mg and subsequent infusions of 500 mg.
Seventeen deaths were reported from the two databases, but none occurred within two weeks of the last Rituxan infusion. Causes of death included suicide, cardiovascular disease, and complications from an MSrelated disability (such as a fall or pneumonia). No deaths from infusion, systemic inflammatory response syndrome, or drug-induced acute coronary syndrome were reported. Similar complications have been reported among patients with cancer who received doses of Rituxan higher than 1,000 mg. The findings suggest that Rituxan at 500 mg or 1,000 mg is a safe option for individuals with MS.50
Meanwhile, retrospective data suggest Rituxan is also effective in pediatric-onset MS. Researchers at Texas Children’s Hospital reviewed MRI scans of 17 patients aged13 to 22 years. These teens and young adults had been diagnosed with MS nine months to nine years before the MRI, and had been treated with Rituxan for a duration of between nine and 46 months. Sixteen patients were relapse-free while receiving Rituxan, while one developed optic neuritis.
Based on the MRI results, 14 of the 17 patients had no T2 or contrast-enhancing lesions and showed no evidence of disease activity. Expanded Disability Status Scale scores also remained stable, with a mean score of 0.5, suggesting near-normal function.51