Overview:
Rituximab is a monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. Rituximab destroys B cells and is therefore used to treat diseases which are characterized by excessive numbers of B cells, overactive B cells, or dysfunctional B cells. This includes many lymphomas, leukemias, transplant rejection, and autoimmune disorders.
Rituximab is approved for non Hodgkin lymphoma and rheumatoid arthritis for example but is prescribed by some neurologists for multiple sclerosis (MS) based upon clinical trials that showed efficacy as a disease modifying therapy (DMT).
Rituxan (rituximab) is an anti-CD20 monoclonal antibody which specifically targets and binds to CD20 expressed on naïve and memory B lymphocytes. It results in the depletion of peripheral CD20 expressing B lymphocytes, and reduces T lymphocytes. CD20 expressing B cells are depleted through antibody dependent cytotoxicity, complement mediated destruction, and antibody mediated apoptosis. The primary mechanism of action of this therapeutic is through the depletion of CD20 expressing B lymphocytes; however the observed reduction in T lymphocytes may also contribute.
Rituxan is delivered by intravenous infusion into the bloodstream every two weeks however protocol towards multiple sclerosis is not defined since the medication is not approved for usage as a disease modifying therapy.
Other trade names include:
- MabThera
- MabThera SC (subcutaneous version)
- Mabtas (biosimilar version)
Rituximab in Relapsing Remitting MS:
In February 2008 results of a one year phase 2 clinical trial involving 104 people comparing the effectiveness of rituximab to a placebo treatment were announced. Participants taking rituximab had a reduced number of new MRI lesions compared to the placebo control group over a period of one year.
They also had a 50% reduction in relapse rate compared to people taking a placebo (dummy) treatment. This remained constant over the one year period.
Rituximab in Primary Progressive MS:
A phase 2/3 trial of rituximab involving 439 people with primary progressive MS reported back in 2009. Although the results are not yet published in a peer reviewed scientific journal, they have been described in a press release. The trial compared rituximab to a placebo treatment but showed that rituximab was not effective.
Rituximab was found to be relatively safe in people with primary progressive MS with most side effects relating to infusion reactions and an increase in infections.
Rituximab in Secondary Progressive MS:
In March 2016 a phase 1/2 clinical trial testing the effectiveness of rituximab in secondary progressive MS was stopped early due to disappointing mid-trial results. This trial involved 27 people with secondary progressive MS, who received rituximab injections directly into the fluid around the spinal cord (intrathecal injection).
Potential Side effects:
Rituximab has been associated with severe side effects such as injection site reactions and progressive multifocal leukencephalopathy though none at this point in time have not occurred in studies to do with MS.
The most common side effects in studies in MS to date were reactions to the infusion and infections.
Possible Other Side Effects Include:
- Allergic reaction
- Itching, hives, swelling in your face or hands, chest tightness
- Headache, nausea, vomiting, stomach pain, cough
- Fatigue, trouble sleeping
- Dizziness, tremor, or changes in vision
- Difficulty urinating
- Increased risk of infections, including progressive multifocal leukoencephalopathy (PML)
- Impaired wound healing
- Difficulty walking or loss of coordination
- Cardiac arrhythmia: palpitations, shortness of breath
- Blood disorders such as anemia or easy bruising or abnormal bleeding
Any adverse events should be reported promptly to a patient’s healthcare team.
Warnings:
Contact your healthcare provider f you are experiencing:
- Chest tightness, trouble breathing, wheezing
- Rash, hives, extreme itchiness
- Swelling of the face, lips, tongue or throat
- High fever, severe sore throat or any other signs of infection
- Fast heartbeat (palpitations), sweating, confusion
- Changes in vision, difficulty walking or loss of coordination
- Bruising, black and tarry stools, blood in urine
- You should not become pregnant or breastfeed an infant while using this medication.
- Contact your physician if you are or if you think you may be or if you would like to become pregnant or breastfeed an infant.
Summary:
Although rituximab itself is not being further developed for MS, based on the encouraging proof-of-principle experience, newer anti-CD20 monoclonal antibodies ocrelizumab and ofatumumab are currently being investigated.
