Rituximab (Rituxan) is a medication approved by the FDA for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.1 It is sometimes prescribed off-label for multiple sclerosis. When a medication is prescribed off-label, it means that the medication is being prescribed for an issue that it is not FDA approved for. Prescribing medications off-label is a common practice, and may be useful when a healthcare provider believes that a medication may be beneficial for treating a particular condition or when other treatment options have been ineffective thus far.
What is rituximab?
Rituximab is a chimeric monoclonal antibody therapy that is manufactured by Genentech and Biogen Idec. Rituximab is sold under the brand name Rituxan. Rituximab decreases the number of B-cells in the body. B-cells are important players in the immune response and are thought to be involved in the development and progression of MS. Rituximab depletes B-cell levels in the body by targeting a protein called CD20. When rituximab binds to this protein that is found on the surface of a B-cell, it may cause that B-cell to self-destruct. This can potentially decrease the overall levels of B-cells in the body, and potentially limit inflammation and MS-related damage.1,2
Where is rituximab in the development process?
Rituximab has been tested in several Phase 2 and Phase 2/3 clinical trials with promising results reported. However, there are currently no completed and published Phase 3 clinical trials on rituximab for MS, and the medication has not yet received FDA approval for this treatment indication. There have been several retrospective studies performed on the effectiveness of rituximab for MS, discussed below, and there are currently several Phase 3 clinical trials in recruitment on rituximab for treatment of MS, as well as one potential Phase 2/3 study and one potential Phase 4 study that may be recruiting in the near future and will investigate rituximab in comparison to other commonly used MS treatment options.3-6
What evidence exists on rituximab for MS?
Results from several Phase 2 and Phase 2/3 studies involving rituximab have been promising. One of these studies reported that rituximab resulted in a 91% reduction in Gd (gadolinium)-enhancing lesions when compared to placebo within a group of individuals with relapsing-remitting MS. Results from this study also indicated that individuals taking rituximab had a lower percentage of relapses than those on placebo.7 A Phase 2/3 study, also known as the OLYMPUS study, reported that participants with primary-progressive MS who were under 51 years old or who had Gd-enhancing lesions at the start of the study experienced a significant improvement in the time to progression while taking rituximab when compared to their counterparts who received a placebo. Furthermore, the OLYMPUS study reported that there was a significantly lower volume of T2 brain lesions on MRI for all participants with primary-progressive MS taking rituximab when compared to placebo.8
A study evaluating the safety of rituximab
Since these two studies, there have been several retrospective analyses published that investigated data from individuals who have previously taken rituximab for their MS. One such review evaluated the safety of rituximab for up to seven years of continuous treatment. The review concluded that the long-term depletion of B-cells as a result of taking rituximab was safe and effective in treating patients with immune-mediated neurological disorders (PIMND), including MS.2 Another retrospective analysis compared rituximab to Tysabri (natalizumab) and determined that rituximab was comparable in safety and efficacy to Tysabri, and may be an appropriate for treatment option for both relapsing-remitting MS and progressive MS.9
A study evaluating comparing rituximab to DMTs
Another retrospective review compared rituximab to multiple different disease-modifying treatments (DMTs), including dimethyl fumarate, fingolimod, and natalizumab, for the initial treatment of relapsing-remitting MS. The study authors found that of the DMTs investigated, rituximab demonstrated significantly lower rates of clinical relapses, lower rates of neuroradiologic disease activity, and fewer adverse events, and may be an appropriate first-line treatment option for RRMS.10
One study for progressive MS was discontinued
However, despite these promising results, one study on rituximab for the treatment of progressive MS was discontinued after B-cells were not being depleted at a significant rate, thus leading the researchers to conclude that the rituximab was ineffective in the study population.11More research, both retrospective and prospective, needs to be completed to strengthen the validity of these findings and to further understand the safety and efficacy of rituximab for MS.
What are the most common adverse effects of rituximab?
The most common side effects of rituximab include, but are not limited to:2
- Infusion reactions (itching, swelling, or rash at the infusion site)
- Body aches
- Increased risk of developing infections