Rituximab
This page covers the following:
Introduction
Rituximab is a powerful drug that can be very effective in treating a spectrum of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. It is currently licensed to treat pemphigus vulgaris but has been shown to be effective in other autoimmune blistering diseases.
What is rituximab used for?
Autoimmune blistering diseases affect the skin and mucosal surfaces such as the mouth, eyes, and genitals. These diseases are caused by antibodies that bind important structural proteins that bind the layers of the skin and membranes together resulting in inflammation and tissue damage. Pemphigus and pemphigoid conditions vary from one another in the targets that these antibodies bind to. For instance, in pemphigus vulgaris, antibodies bind proteins called desmoglein 1 and 3 which are important for the bonds that link keratinocytes together. Keratinocytes are the building blocks of the skin and essential for its structural integrity. When antibodies bind desmoglein 1 and 3, these bonds are weakened which causes separation of keratinocytes and the formation of a blister.
Antibodies are produced by cells known as B cells and plasma cells. B cells are a type of white blood cell that proliferate when they are activated and develop into plasma cells. If you have pemphigus or pemphigoid, you will have families of B cells and plasma cells that produce the antibodies which cause your disease. Treatments for these diseases are therefore focussed on preventing the proliferation of these cells or destroying them in order to reduce the number of disease-causing antibodies.
What is rituximab and how does it work?
Rituximab is a bioengineered antibody that binds a protein known as CD20 which is found on the surface of B cells. When rituximab binds CD20, it causes B cells to die rapidly, and therefore the drug results in the destruction of the majority of your body’s B cells. Unlike B cells, plasma cells do not express CD20 and are therefore not directly targeted by rituximab. However, the numbers of plasma cells are thought to fall over the months following rituximab treatment due to their short life span and the fact that there are no B cells to replenish them. The reduction in the number of B cells and plasma cells causes a fall in the number of disease-causing antibodies which is usually associated with clinical improvement, although this can take up to 6 months. Eventually new B cells are produced by the bone marrow and B cells start to repopulate in the blood and tissues. The time that it takes for B cells to repopulate varies significantly but is usually between 1 to 2 years after receiving rituximab. B cell repopulation can be associated with a relapse in the disease and often repeat treatment with rituximab is required.
How is it is administered?
Rituximab is normally administered as a round of 2 infusions given 2 weeks apart. Each infusion involves inserting a cannula or drip into a vein in your arm. You will usually be given paracetamol, steroids, and antihistamine at the time of the infusion to reduce the risk of any side effects resulting from your body’s immune system recognising the drug. Each infusion usually takes 4-6 hours as it needs to be administered slowly. The initial infusion generally takes the longest. Blood pressure, heartrate and oxygen saturation measurements are monitored every 30 minutes during the infusion. If subsequent treatments are required, they may be given as single or double infusions (spaced over 2 weeks) depending on symptoms and infusion history. Any subsequent treatments are given at least 6 months apart.
What are the risks and side effects of treatment?
The most common side effects are related to your immune system recognising the drug during the infusion, causing an infusion reaction. This can cause redness and discomfort at the site of the cannula. Some people can also experience fever, headache, wheeze, or cough. Rarely, the infusion can cause a severe allergic reaction resulting in anaphylaxis where there is a drop in blood pressure and swelling of the upper airways. For this reason, rituximab is administered in hospital where there are facilities to treat this rare but serious side effect.
Long term side effects of rituximab are mainly related to an increased risk of infection. Rituximab removes the dangerous B cells that cause the disease but also destroys the B cells that fight infections, and these remain depleted for 1-2 years after the treatment. The effects of rituximab are therefore irreversible and long lived. During the period of B cell depletion, you will have an increased risk of infection of any type and a significant reduction in your ability to mount immune responses to vaccines. For this reason, it is very important that you are up to date with vaccinations before you have the treatment. This is especially important with the COVID-19 vaccination as more severe COVID-19 infections have been observed in unvaccinated people who have received rituximab.
Why doesn’t everyone with an autoimmune blistering disease get rituximab?
Rituximab is licensed for the treatment of pemphigus but can be used in other immunobullous conditions. Because rituximab is a powerful and long-lasting drug it is generally given to patients who have severe disease despite treatment with first line immunosuppressive agents such as mycophenolate mofetil. It is licensed for the treatment of pemphigus because there is good evidence for its effectiveness for this condition. Its effectiveness in the treatment of conditions such as bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa aquisita is more variable although it can be effective in these conditions.
Research, particularly studies in France by Professor Pascal Joly, has shown that rituximab is more effective when administered as a first line treatment. The All Wales Therapeutics and Toxicology Centre have approved rituximab as a first-line treatment for pemphigus vulgaris. In England and Scotland, rituximab is only approved once two other treatments have failed or have created serious side-effects.
Summary
Rituximab is a powerful drug that targets B cells and results in a reduction in the antibodies that cause immunobullous diseases. Rituximab is normally administered as intravenous infusions administered 2 weeks apart, although there may be subsequent treatments as single or double infusions as required. The main side effects are infusion reactions and an increased susceptibility to infection. The effects of rituximab are long lasted although relapse in the disease is common and often patients require multiple treatments.