Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting the joints and skin that arises when the immune system mistakenly targets healthy tissue. This leads to pain, swelling, and possible joint damage. To manage PsA, doctors often prescribe immunosuppressive medications, which help reduce inflammation, prevent joint damage, and improve overall quality of life.

Immunosuppressant drugs dampen the immune system’s overall activity. Immunomodulatory drugs, on the other hand, focus on specific immune cells and proteins.

Disease-modifying antirheumatic drugs (DMARDs) are a broad category of medications used to treat psoriatic arthritis and other autoimmune conditions. DMARDs encompass both immunosuppressants and immunomodulatory medications. DMARDs work by modifying the immune system to reduce inflammation and slow down joint damage, often preventing the condition from worsening over time.

Below is a detailed look at six types of immunosuppressant and immunomodulatory medications commonly used to manage PsA, along with an explanation of how each type works.

1. Traditional DMARDs

Traditional, or conventional, DMARDs are commonly used to treat PsA, either alone or in combination with biologic DMARDs. This class of DMARDs is considered to be immunosuppressant, as they work differently to dampen the immune system as a whole. The following are examples of traditional DMARDs.

Methotrexate

Methotrexate is a standard treatment for PsA, especially for those who are new to treatment. Although it is commonly prescribed, methotrexate is actually used “off-label” for PsA, as it is not specifically approved by the U.S. Food and Drug Administration (FDA) for this condition. Brand names include Trexall, Jylamvo, and Xatmep.

Methotrexate works by stopping immune cells from producing DNA, which slows their growth and reduces inflammation. This helps protect joints from damage and keeps symptoms under control. However, methotrexate can affect the liver and immune system, so people may need regular blood tests to check for side effects like liver damage or lower blood cell counts, which could increase infection risk.

Leflunomide (Arava)

Leflunomide is another traditional DMARD used off-label for PsA. This treatment slows immune cell activity by blocking the production of DNA. This reduces inflammation and prevents the immune system from attacking the joints. It can be effective for many people but may cause side effects such as diarrhea, liver problems, and sometimes hair loss. Regular monitoring is necessary to ensure the medication is safe and effective for long-term use.

Sulfasalazine (Azulfidine)

Sulfasalazine combines anti-inflammatory and antibiotic properties to manage PsA. This drug is also used off-label. It reduces inflammation by interfering with certain immune responses and also limits joint damage. While beneficial for many people, it can cause stomach issues like nausea, and it might lower white blood cell counts, which can increase infection risks. Regular check-ups help ensure any side effects are managed early.

2. Tumor Necrosis Factor-Alpha Inhibitors

Tumor necrosis factor-alpha (TNF-alpha) inhibitors are a class of biologic drugs that block the activity of TNF-alpha. TNF-alpha is a cytokine (type of protein) responsible for telling immune cells to create inflammation. High levels of TNF-alpha are found in the joints of people with PsA. Different sources describe TNF inhibitors as immunosuppressant or immunomodulatory. Ultimately, these medications are intended to reduce inflammation.

Several TNF inhibitors are FDA-approved to treat PsA. These medications are injected. All of these medications carry the risk of side effects, including increased risk of infections (such as upper respiratory tract infections) and allergic reactions. Before starting certain TNF inhibitors, a person may be screened for tuberculosis (TB) and will typically be monitored regularly during treatment to manage any possible complications.

Long-term use of TNF inhibitors has been linked to an increased risk of certain cancers, so regular medical check-ups are necessary.

Some TNF inhibitors may also have biosimilars available. Biosimilars are highly similar to previously approved biologic medications but are often more affordable. Your doctor can help you understand if a biosimilar is appropriate for you.

Etanercept (Enbrel)

Etanercept binds to TNF-alpha, preventing it from causing inflammation. Etanercept is effective for both joint and skin symptoms of PsA.

Adalimumab (Humira)

Adalimumab blocks TNF-alpha from interacting with immune cells. Adalimumab helps to reduce inflammation and control symptoms like joint pain and skin rashes.

Golimumab (Simponi)

Golimumab works by attaching directly to TNF-alpha and neutralizing it. This prevents the protein from interacting with receptors on immune cells. As a result, it helps to reduce inflammation, joint pain, and swelling.

Certolizumab Pegol (Cimzia)

Certolizumab is another biologic that works similarly to golimumab and binds directly to TNF-alpha. By neutralizing TNF-alpha, certolizumab reduces joint pain, swelling, and stiffness.

Infliximab (Remicade)

Infliximab works similarly to both certolizumab and golimumab by binding directly to TNF-alpha and neutralizing it.

3. Interleukin Inhibitors

Interleukin (IL) inhibitors are another class of biologic drugs used to treat PsA. Like TNF inhibitors, they are injected. Interleukins are a group of proteins that tell immune cells to turn on and cause inflammation. Particularly, high levels of the proteins IL-12, IL-23, and IL-17A are associated with inflammation in PsA.

IL-inhibitors work by blocking these specific IL proteins, which can decrease inflammation, relieve joint pain, and prevent further joint damage. These are considered targeted therapies and therefore fall under the classification of immunomodulatory. Some IL inhibitors also have biosimilar options.

Common side effects for these medications can include an increased risk of infections, headaches, and nausea. Your doctor should discuss potential side effects with you, help identify which ones may require medical attention, and outline any monitoring needed to ensure safe treatment.

Secukinumab (Cosentyx)

Secukinumab targets IL-17A, which plays a key role in inflammation in PsA. This medication is particularly useful for those who have not responded well to TNF inhibitors.

Ustekinumab (Stelara)

Ustekinumab works by blocking two proteins involved in inflammation, IL-12 and IL-23. It is effective for people who have both skin and joint symptoms.

Ixekizumab (Taltz)

Ixekizumab, similar to secukinumab, targets IL-17A to reduce inflammation. It helps with both joint and skin symptoms and is suitable for people with moderate to severe PsA.

Risankizumab-Rzaa (Skyrizi)

Risankizumab-rzaa targets IL-23, which specifically helps manage both joint and skin symptoms. After its initial dosing, it is self-administered every 12 weeks, making it a convenient long-term treatment option.

Guselkumab (Tremfya)

Guselkumab targets IL-23 like risankizumab-rzaa. However each drug targets different portions of the IL-23 protein. After its initial dosing, it is taken every eight weeks, making it another practical choice for long-term management.

4. Selective Costimulation Modulators

In PsA, the body makes too many immune cells called T cells, which can drive inflammation, pain, and swelling. This class of medications includes both a targeted therapy and an immunosuppressant.

Abatacept (Orencia)

Abatacept targets T cell activation (when T cells are “switched on” to fight a harmful substance). T cell activation contributes to inflammation in psoriatic arthritis. While generally well-tolerated, abatacept can increase the risk of infections, so regular monitoring is important to ensure the treatment remains safe and effective. This medication is injected.

Cyclosporine (Gengraf, Neoral, SandImmune)

Cyclosporine is an oral immunosuppressant medication that works by inhibiting the activity of T cells. By blocking T cell activation, cyclosporine helps reduce inflammation and alleviate joint symptoms.

Due to its strong immunosuppressive effects, cyclosporine carries a risk of side effects, including kidney damage, hypertension (high blood pressure), and increased risk of infections. You will need regular monitoring of kidney function and blood pressure while taking this drug.

5. Phosphodiesterase 4 Inhibitors

Phosphodiesterase 4 (PDE4) is an enzyme that plays a role in inflammation in PsA. PDE4 inhibitors are considered a targeted immunomodulatory therapy. As of November 2024, there is only one PDE4 inhibitor FDA-approved for PsA: Otezla, a formulation of apremilast.

Apremilast (Otezla)

Apremilast works differently from biologics. It specifically targets PDE4 to reduce inflammation inside immune cells. It is taken as a pill and is a good option for those who want to avoid injections. Common side effects include headaches, diarrhea, and weight loss. Those with a history of depression should discuss this with their doctor, as apremilast has been linked to mood changes in some people.

6. Janus Kinase Inhibitors

Janus kinase (JAK) proteins are inflammatory messengers that promote inflammation and overactivation of the immune system, especially in the case of PsA. Although some health experts consider JAK inhibitors to be targeted therapies, others categorize them as immunosuppressants due to their broad effect on the immune system. JAK inhibitors are taken as pills. As of November 2024, two JAK inhibitors have been FDA-approved to treat PsA.

Upadacitinib (Rinvoq)

Upadacitinib reduces inflammation by targeting the JAK enzymes involved in immune responses. It is particularly helpful for people who prefer oral medications over injections.

Upadacitinib can increase the risk of blood clots, liver problems, and serious infections. Those taking upadacitinib often undergo regular blood tests to monitor for these side effects and adjust treatment if necessary.

Tofacitinib (Xeljanz)

Like upadacitinib, tofacitinib targets specific JAK enzymes involved in triggering inflammation in psoriatic arthritis. It also carries similar risks, including higher likelihood for infections and blood clots. It may cause elevated cholesterol levels. Regular monitoring is often recommended.

Key Facts About Taking Immunosuppressive and Immunomodulatory Drugs

When taking DMARDs for PsA, it’s important to be aware of the risks and necessary precautions.

They Increase the Risk of Infections

These drugs can reduce your immune system’s ability to fight infections, making you more vulnerable to illnesses such as colds, pneumonia, or even TB. When taking these types of drugs, it’s crucial to do the following:

• Practice good hygiene.
• Avoid contact with people who are sick.
• Get vaccinated against preventable disease, such as the flu.

However, you should avoid live vaccines (such as the measles or yellow fever vaccine), as they can cause serious illness in people with weakened immune systems.

Regular Monitoring Is Necessary

Many DMARDs require frequent blood tests to check for side effects like liver or kidney damage. This helps doctors adjust treatment to keep people safe.

Other Health Conditions Can Affect Treatment

PsA often coexists with other health issues, such as diabetes or inflammatory bowel disease (IBD). Having these types of conditions can affect which treatment options are safest and most effective for you. It’s important to work with your health care provider to adjust your treatment plan based on any other conditions you have.

They Can Interact With Other Drugs

Some medications and supplements can interact with immunosuppressants and immunomodulatory drugs, potentially reducing their effectiveness or increasing side effects. Be sure to inform your doctor about any other treatments or supplements you are taking.

By following these guidelines and working closely with your health care team, you can effectively manage PsA while minimizing the risks associated with immunosuppressive treatments.

Talk With Others Who Understand

MyPsoriasisTeam is the social network for people with psoriatic arthritis and psoriasis and their loved ones. More than 131,000 members come together to ask questions, give advice, and share their stories with others who understand life with psoriatic disease.

Have you used DMARDs to treat your psoriatic arthritis? Share your experience in the comments below, or start a conversation by posting on MyPsoriasisTeam.