How it works: Immune suppression and rheumatoid arthritis

The immune system is the body’s natural defense system against invaders that can make a person sick, such as viruses and bacteria.

In a healthy body, there are checks and balances in place that help the immune system recognize the body’s own tissues from foreign invaders. Experts call this ability self-tolerance.

In RA, however, this ability is lost. As a result, the immune system fails to recognize tissues in the joints as its own and instead mounts a response that leads to swelling, pain, and tissue damage.

The loss of self-tolerance is the basis of all autoimmune conditions. Although the precise cause of autoimmunity often remains unknown, health experts believe these conditions develop due to a combination of:

• genetics
• exposure to various substances, such as cigarette smoke
• physical or emotional stress
• viral or bacterial infection

Although symptoms of RA typically start in the hands, knees, or ankles, autoimmunity is not confined to the joints alone. As the condition progresses, the immune system may attack other organs in the body as well, including the:

• eyes
• skin
• heart and blood vessels
• lungs

Therefore, RA treatment aims to not only reduce pain and swelling but also suppress the immune system to prevent damage to the joints and other organs of the body.

Doctors typically treat RA with various types of immunosuppressants. The type they choose will depend on the severity of the condition, among other factors.

General immunosuppressants

In most cases, doctors will initially start a person with RA on a medication to control inflammation and reduce pain. This often consists of either a nonsteroidal anti-inflammatory drug (NSAID) or corticosteroids.

Some common NSAIDs that doctors may use for RA include:

• acetylsalicylate (aspirin)
• naproxen (Aleve, Naprosyn)
• ibuprofen (Advil, Motrin)
• etodolac (Lodine)

Corticosteroids are stronger anti-inflammatory medications than NSAIDs, but they tend to have more side effects. That is why healthcare professionals often recommend them only for short periods, such as during flares.

Doctors often use NSAIDs or corticosteroids together with a DMARD, which works to slow or stop the destruction of tissues in the joints. Whereas NSAIDs and corticosteroids help control symptoms, these medications help promote remission.

The DMARDs that doctors most commonly use to treat RA are:

• methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo)
• hydroxychloroquine (Plaquenil)
• leflunomide (Arava)
• sulfasalazine (Azulfidine)
• tofacitinib (Xeljanz)
• baricitinib (Olumiant)

These medications work to suppress the immune system in different ways.

Hydroxychloroquine, tofacitinib, and baricitinib, for example, block communication between immune cells. Methotrexate, on the other hand, interferes with processes that allow immune cells to grow and divide.

Biological disease modifiers

For people with more severe disease activity, doctors may use medications that target the specific underlying biology of RA, known as biologics.

A variety of biologics are available for the treatment of RA. These are injectable agents that target either:

• Signaling molecules between immune cells: This includes medications such as:
  • adalimumab (Humira)
  • anakinra (Kineret)
  • certolizumab (Cimzia)
  • etanercept (Enbrel)
  • golimumab (Simponi)
  • infliximab (Remicade)
  • sarilumab (Kevzara)
  • tocilizumab (Actemra)
• Antibody-producing B cells: This includes drugs such as rituximab (Rituxan).
• Other immune cells: This group includes abatacept (Orencia), which turns off T cells that cause inflammation.

Doctors may use these medications on their own or, more commonly, in combination with methotrexate.

As with all medications, there is a risk of side effects when taking immunosuppressants.

These agents work by inhibiting the immune system, and therefore, people taking immunosuppressants are more likely to develop infections or have trouble recovering when they get sick.

This risk is highest with the use of biologic agents. According to an analysis of 106 clinical trials, people taking a standard dose of a biologic medication were 31% more likely to develop a serious infection than those who received a traditional DMARD. Those taking a high dose biologic medication were 90% more likely to have a serious infection.

However, research suggests that this risk is not universal and that the risk may be higher with certain types of medications within these larger umbrellas.

One study found that, during the COVID-19 pandemic, people with RA who received rituximab, tofacitinib, or baricitinib were more likely to have severe COVID-19 than those using other types of treatments.

These medications all work in different ways to inhibit immune activity. It is therefore important for people with RA to consult a rheumatologist about possible side effects and risks of infection.

RA is an autoimmune condition that leads to inflammation and tissue damage in the joints. Treatment relies on suppression of the immune system, which limits destruction and prevents disease progression.

People taking certain types of immunosuppressants may be more likely to develop infections.

It is important to seek guidance from a rheumatologist about the risks and benefits of immune suppression during RA treatment.