Oral treatments can help control the inflammation and pain that come with psoriatic arthritis (PsA). Some types of pills and tablets are used when you’re first diagnosed, while others may not be suggested unless other treatment options don’t work. Here, we’ll discuss the four main types of oral medications that treat joint pain and inflammation in PsA, as well as their side effects.

1. Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used as a first-line treatment for PsA. NSAIDs are available over-the-counter (OTC) at pharmacies and grocery stores or by prescription from your doctor. OTC medications tend to come in lower doses to help treat mild joint pain and swelling.

Prescription NSAIDs are available in higher doses to treat more severe symptoms. Some people can manage their PsA using only NSAIDs. However, these drugs don’t stop disease progression in the joints. Your doctor may recommend combining them with disease-modifying antirheumatic drugs (DMARDs) to control symptoms and disease progression.

NSAIDs work by blocking the function-specific enzymes that contribute to inflammation. Some examples of NSAIDs include aspirin, ibuprofen, and naproxen.

You may not be able to take NSAIDs if you have certain health conditions, such as high blood pressure, cardiovascular disease, diabetes, or kidney problems. Some NSAIDs have blood-thinning effects, which can make these conditions worse. Other side effects include:

• Heartburn
• Stomach pain
• Bleeding
• Headaches
• Dizziness or lightheadedness
• Increased blood pressure
• Ringing in the ears
• Buildup of extra fluid in the body

If you notice any of these symptoms, talk to your doctor. They may recommend a different NSAID that has fewer side effects.

2. Oral Disease-Modifying Antirheumatic Drugs

DMARDs are a class of medications that help slow joint damage and reduce pain and swelling. Some also help reduce psoriatic skin lesions. Oral DMARDs may be one of the first pills your rheumatologist prescribes for PsA. Each DMARD works slightly differently to block inflammation and relieve PsA symptoms.

Methotrexate

Methotrexate is the most common DMARD used to treat PsA. It interferes with the DNA repair process in cells, which helps prevent immune cells from multiplying. As a result, inflammation decreases.

You’ll take methotrexate as a weekly dose, and you’ll need to have your liver, kidney, and lung function monitored while you’re on this medication. Methotrexate improves both joint symptoms and skin lesions.

Most people taking methotrexate have mild side effects that typically go away after some time. If you’re taking a higher dose, you may experience:

• Hair loss
• Nausea or upset stomach
• Diarrhea
• Abnormal blood cell counts
• Liver problems
• Increased sensitivity to the sun
• Ulcers in the mouth

This medication can be administered orally or as an injection in the skin. Side effects are more common with oral administration.

Leflunomide

Leflunomide (Arava) is another DMARD used to treat PsA. Leflunomide prevents the production of DNA building blocks, which stops immune cells from multiplying. Your healthcare provider may prescribe leflunomide alone or along with other DMARDs. Your liver function should be monitored periodically when taking leflunomide.

Common side effects of leflunomide include:

• Diarrhea (most common)
• Hair loss
• Stomach pain
• Nausea or indigestion
• Rashes
• Liver problems
• Increased risk of infections

Sulfasalazine

Sulfasalazine (Azulfidine) differs from other DMARDs — it contains two drugs, an antibiotic and salicylate (the active ingredient in aspirin). Researchers aren’t quite sure how sulfasalazine treats inflammation in PsA, but they think it may block inflammatory signals and immune cells. It tends to be used less often than other DMARDs.

Do not take sulfasalazine if you’re allergic to sulfa drugs. People tend to have fewer side effects taking sulfasalazine. The most common include:

• Headaches
• Nausea
• Upset stomach
• Loss of appetite
• Skin rashes
• Increased sensitivity to the sun

Cyclosporine

Originally used to help prevent the immune system from rejecting organ transplants, cyclosporine can also help treat cases of PsA with severe joint inflammation or skin problems. Cyclosporine is highly effective and is often used for only short periods. Symptoms usually start improving within a few weeks, but it may take up to a few months for you to experience the full effects.

Side effects of cyclosporine include:

• Kidney problems
• High blood pressure
• Nausea or vomiting
• Headaches
• Swelling of the hands or feet
• Numbness or tingling in the hands or feet
• Tremors (uncontrollable shaking)

3. Phosphodiesterase-4 Inhibitors

Phosphodiesterase-4 (PDE4) inhibitors lower levels of chemical messengers known as cytokines, which are responsible for producing inflammation. The only PDE4 inhibitor that is approved by the U.S. Food and Drug Administration (FDA) for treating PsA is Otezla, a formulation of apremilast.

According to the National Psoriasis Foundation, apremilast can be combined with methotrexate, phototherapy, or topical medications. This drug is often prescribed when DMARDs do not improve symptoms or when a person is allergic to biologic drugs.

Side effects of apremilast include:

• Nausea and vomiting
• Diarrhea
• Weight loss
• Headaches
• Upper respiratory infections
• Depression

4. Janus Kinase Inhibitors

Janus kinase (JAK) inhibitors are a more recent option for treating psoriatic arthritis. They are usually only prescribed if other treatments, like biologics, are not effective. Cytokines attach to JAK proteins on the outside of cells, sending inflammation signals inside. JAK inhibitors prevent these chemical messengers from attaching to the proteins, which helps stop inflammation and reduces joint pain and swelling.

Currently, two JAK inhibitors are FDA-approved to treat psoriatic arthritis:

• Tofacitinib (Xeljanz)
• Upadacitinib (Rinvoq)

You may notice your symptoms improving within a few weeks of starting this daily treatment, but JAK inhibitors can take three to six months to begin fully working.​

In general, JAK inhibitors come with fewer side effects than other PsA medications. This is because they specifically target JAK proteins. Common side effects include:

• Headaches
• Nausea or indigestion
• Diarrhea
• Increased cholesterol levels
• Upper respiratory tract infections
• Acne

Throughout your treatment with JAK inhibitors, your rheumatologist will also run blood tests to ensure your blood counts and lipids (fats in the blood) are normal and your organs are working well. Testing for tuberculosis is also done yearly.

In September 2021, the FDA added a requirement that the prescribing information for certain JAK inhibitors, including tofacitinib and upadacitinib, carry specific black box warnings about the risk of heart-related events, blood clots, and cancer. If you are considering JAK inhibitors or currently take one, your doctor can help you understand any risks associated with the medication.

Talk With Others Who Understand

By joining MyPsoriasisTeam, the social network for people living with psoriasis and psoriatic arthritis, you’ll gain a support group of others who understand what you’re going through.

Are you taking oral medication for PsA? What has worked for you? Have you had any side effects from these drugs? Share your experiences in the comments below, or start a conversation by posting on your Activities page.