Immunosuppressive Drugs: Strategies for Staying Healthy

Immunosuppressive drugs reduce the activity of the immune system. They are vital for controlling severe cases of lupus that do not respond to other medications. But, they also leave the body susceptible to infection.

The immune system is a little bit like gate security at a concert. It protects our bodies from invaders. However, for people with lupus and other autoimmune diseases, this security is out of control. It attacks the very body that it is meant to protect, causing damage and compromising your health.

Immunosuppressive drugs, also called immunosuppressants, stop the activity of the immune system. Because lupus is caused by the immune system, suppressing the immune system can reduce the symptoms of all forms of lupus.

Immunosuppressants are also used to treat some types of cancer and allergies, plus they can reduce complications during organ transplants.

There are a variety of immunosuppressive drugs, each with a different way they effect the body – also called a “mechanism of action.” Each class of medication works on a different part of the immune system, disrupting it in various ways.

Lupus Warriors do not all have the same experiences with every medication. Researchers are working to fully understand the biologic markers and pathways associated with lupus. Identifying and then using the most appropriate medication (and even creating personalized blends) for an individual is known as personalized medicine.

Finding the right immunosuppressant for each person with lupus can maximize the benefits, because these drugs come with serious risks. The biggest risk is the risk of infection, as the body is left relatively undefended against invading bacteria, fungus, and viruses.

Still, the benefits of a lower-symptom life may outweigh these risks.

What immunosuppressive drugs are used for lupus?

Lupus Warriors use many immunosuppressive weapons in their battle. The medication prescribed depends on other medications being taken, symptoms, and co-morbid conditions. For example, some medications are useful for lupus nephritis (lupus with kidney symptoms) while others stress the kidneys and are not appropriate.  You can read more about lupus nephritis here.

 A few medications used more commonly for lupus include:

• Cyclophosphamide, also known as Cytoxan
• Methotrexate, also known as Reumatrex.
• Azathioprine, also known as Imuran
• Mycophenolate, also known as Myfortic

Most of these are delivered intravenously, so they require special equipment not usually found in the average home. Although generally administered at hospitals or at care facilities, some can be prepared at home.

How do they work?

The immune system is a complex machine, and immune system suppressing medications work by throwing a wrench into different parts of the machine. Often, they inhibit particular proliferation or signaling features of the immune system.

As of 2020, many of these medications have been developed. These different types of medications are called “classes” and have different interactions with lupus and lupus medications.

DNA Synthesis-Interfering Medications

Many immunosuppressants used for lupus, including mycophenolate, methotrexate, cyclophosphamide, and azathioprine work right at the beginning of immune system function. They interfere with DNA synthesis in the nucleus of the immune system’s cells.

Preventing DNA synthesis blocks these cells from replicating and regenerating. All cells in the body need DNA synthesis to replicate, regenerate, and function. However, immune system cells have to divide rapidly to adapt to threats and to produce the specialized soldier cells that hunt down and attack pathogens. This process of rapid replication is also known as “proliferation.”

By preventing cell division, the numbers of immune system warriors like T-Cells and B-Cells and macrophages are kept low. Immune cells also become less able to produce proteins important to the immune response, such as antibodies. The right doses of these medications keeps this from going too far and killing the cells (and other cells) entirely.

Cyclosporine, a medication sometimes used to treat lupus, works differently. It targets calcineurin receptors, the trigger mechanisms for the soldier cells. Specifically, for the T- family of immune cells. You can read more about these cells, also known as T-cells, here.  Calcineurin inhibitors like cyclosporine can also affect the ability of blood vessels to constrict or expand, increasing blood pressure and potentially injuring the kidneys.

A newer style of therapy avoids calcineurin inhibitors in order to avoid these side effects. While not commonly used, it may be prescribed “off label” and is considered effective.

B Cell Inhibitors

B cells are targeted by many immunosuppressant medications that started off as anti-cancer regimens, including Rituximab.

These medications stop growth and activity of B cells during their development. They are able to target the correct cells by identifying CD20 or CD22, proteins that are only found on the membrane (outer coat) of immune system cells.

B cell inhibitors can even trigger the cells to destroy themselves (a process called apoptosis). At the same time, since these proteins are not on any other type of cell, their effects on other cells are relatively minimal.

However, medications that target CD20 and B-cells can also reactivate Hepatitis B, an infection that will easily overwhelm an immunosuppressed body. People who are candidates for taking medications such as Rituximab have to be screened for hepatitis B surface antigen and hepatitis B core antibody to make sure that it is not present before use.

On the other hand, Belimumab, sold under the brand name Benlysta, acts during B cell division. This prevents the B cell-activating factor, also known as BAFF or BLyS, from binding to the cells. BAFF encourages the cells to divide and mature and prevents them from undergoing apoptosis and dying. Belimumab turns this off, stopping cell division, cell growth, and encouraging cell death.

TNF-a Inhibitors

Tumor Necrosis Factor Alpha (or TNF- α for short) is an immune system particle (or cytokine) that the immune system uses against the body’s own cells. It is produced by special immune system cells that seek out abnormal cells in the body and causes a chain reaction in those cells that leads to cell death.

When used correctly, it is an effective weapon against tumors (the body’s own cells grown out of control) and against retroviruses (which hide in host cells and use those cells to produce more virus).

In autoimmune disease, this weapon is used against even healthy cells, damaging vital organs. TNF- α inhibitors block the attachment sites (receptors) where the cytokines connect to the cell. This keeps the deadly chain reaction from starting in the first place, and prevents damage to the body.

Interleukin Inhibitors

Interleukins (there are many) are like immune system alarms. When a cell is damaged and destroyed, it releases interleukins. These call immune system cells to that site to fight whatever caused the damage. When the cause of the damage is the immune system itself, as in autoimmune disease, these alarms will only make the problem worse!

Interleukin inhibitors (including Tocilizumab) prevent the immune system from “hearing” the alarms. They attach to the receptors that normally would sense interleukins. Since the interleukins cannot attach, they cannot call the immune system into action. And, the immune system cells don’t go on the attack against the body’s own cells.

In all cases, these medications interfere with some aspect of immune system function, reducing the overall response.

Other Side Effects of Immunosuppressive Drugs

Aside from making people more vulnerable to disease, immunosuppressive medications have other effects on the body. This is because of the complicated machinery of the body – affecting the immune system can cause unintended side effects. Depending on the medication, these side effects can include:

• Stomach issues (nausea, vomiting, diarrhea, or stomach ulcers)
• Rashes
• Liver inflammation
• Bleeding (due to affecting the bone marrow)

And rarely severe side effects such as:

• Fever and chills (signs of an allergic reaction)
• Pancreas inflammation
• Increased risk of cancer

These symptoms warrant a call to emergency services and, potentially, a hospital visit.

Keeping Yourself Healthy on Immunosuppressive Drugs

Because these medications suppress the immune system, people who take these medications need to take additional precautions in their everyday life. This can be a valid reason for anxiety – but there are many things that you can do about it.

Here are the basics, according to the National Institutes of Health:

• Take care of your basic health: eat a balanced diet, get plenty of sleep, and get exercise.
• Protect yourself and your body: when going outside. And especially when going into risky areas (such as large groups of people.) Use protective gear like face masks and gloves.
• Get your family on board: if you have visitors or live with others. They could bring in pathogens and make you sick. To protect yourself, make sure that they take precautions too!
• Keep your space and yourself clean: Hygiene can help prevent many diseases, and you can read more about it here. It’s worth getting help to clean your home if you need it – and it can potentially keep you safe.

You can read more about preventing infections here.