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Immunosuppressant Medications for Psoriatic Arthritis: How Do They Work?

Posted on May 06, 2021
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Emily Wagner, M.S.

Immunosuppressant medications are used to treat psoriatic arthritis (PsA) and other autoimmune diseases such as rheumatoid arthritis. PsA is caused by long-lasting inflammation in the body, due to a person’s immune system attacking their own joints. Most medications for PsA focus on dampening the immune system.

Immunosuppressants and Disease-Modifying Antirheumatic Drugs

Immunosuppressant drugs are small-molecule drugs that work to dampen the immune system as a whole. This effect puts people at an increased risk for infections. Examples of immunosuppressant drugs include Sandimmune (cyclosporine), a drug that shuts down a type of immune cell known as T cells, preventing them from contributing to inflammation. Imuran (azathioprine), meanwhile, stops immune cells from making new DNA molecules, preventing them from dividing and causing inflammation

Immunomodulatory drugs, on the other hand, do not suppress the whole immune system. Rather, they target specific immune cells and their proteins. Disease-modifying antirheumatic drugs (DMARDs) are an example of immunomodulatory drugs.

DMARDs work by modifying the immune system and stopping inflammation at its source. This effect can help slow, and even prevent, further joint damage associated with PsA. Examples of DMARDs used to treat PsA include chemotherapies, biologics, and Janus kinase (JAK) inhibitors.

DMARDs can also be combined with other drugs commonly used to treat autoimmune conditions, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil (ibuprofen) and Aleve (naproxen). NSAIDs typically treat only the symptoms of inflammation and cannot target it at its source.

Traditional DMARDs for Psoriatic Arthritis

Traditional or conventional DMARDs are commonly used to treat PsA, either alone or in combination with biologic DMARDs. Corticosteroids such as prednisone can also be combined with traditional DMARDs to alleviate symptoms. Often, conventional DMARDs are also used as chemotherapy drugs to treat cancers. Examples include:

  • Methotrexate, which is commonly prescribed as a first-line treatment for PsA and has broad effects on immune cells and markers of inflammation
  • Arava (leflunomide), which blocks immune cells from making new DNA, stopping them from dividing and contributing to inflammation
  • Azulfidine (sulfasalazine), which contains sulfapyridine (an antibiotic) and salicylic acid (found in aspirin) to help fight inflammation and oxidative stress

Biologic DMARDs for Psoriatic Arthritis

Biologics are human-made molecules that can be engineered to target specific parts of the immune system. There are three classes of biologics used to treat PsA: tumor necrosis factor alpha (TNFA) inhibitors, interleukin (IL) inhibitors, and selective costimulation modulators.

Tumor Necrosis Factor Alpha Inhibitors

Tumor necrosis factor alpha is a special protein, known as a cytokine, that is responsible for telling immune cells to create inflammation. TNFA is found at high levels in the joints of people with PsA, where it binds to receptors on the outside of cells. Engineered proteins have been developed to block TNFA in a few different ways:

Interleukin Inhibitors

Interleukins are a group of proteins that tell immune cells to turn on and cause inflammation. Particularly, high levels of the proteins IL12, IL23, and IL17A are associated with inflammation in PsA. IL inhibitors work by blocking these proteins, which can decrease inflammation and relieve joint pain and damage. Examples include:

Selective Costimulation Modulators

In PsA, the body makes too many immune cells called T cells, which can lead to inflammation, pain, and swelling. Orencia (abatacept) is a selective costimulation modulator that disrupts communication between T cells.

PDE4 Inhibitors

One enzyme that plays a role in inflammation in PsA is phosphodiesterase 4 (PDE4), which is used to activate immune cells. Otezla (apremilast) is a PDE4 inhibitor that works inside immune cells to limit the enzyme’s activity, reducing inflammation in the body.

Janus Kinase Inhibitors

JAK proteins are inflammatory messengers that can be overproduced in autoimmune diseases, which promotes inflammation and overactivation of the immune system, especially in the case of PsA. Xeljanz (tofacitinib) is a JAK inhibitor that blocks all three JAK proteins (JAK1, JAK2, and JAK3).

Talk With Others Who Understand

MyPsoriasisTeam is the social network for people with psoriatic arthritis and psoriasis and their loved ones. More than 92,000 members come together to ask questions, give advice, and share their stories with others who understand life with psoriatic disease.

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

All updates must be accompanied by text or a picture.
Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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