Oral treatments — medications taken by mouth — can help control inflammation and pain caused by psoriatic arthritis (PsA). Some pills and tablets are used early after diagnosis, while others are used only if other treatments for PsA don’t work.

This article covers five main types of oral medications used to treat joint pain and inflammation in PsA, along with their possible 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 options usually come in lower doses for mild joint pain and swelling.

NSAIDs work by blocking enzymes that cause inflammation. Common examples include aspirin, ibuprofen, and naproxen.

Prescription NSAIDs come in higher doses to treat more severe symptoms. Some people manage PsA symptoms with NSAIDs alone.

However, NSAIDs don’t slow disease progression or prevent joint damage. They only help relieve pain. Your doctor may suggest using them along with disease-modifying antirheumatic drugs (DMARDs) to better control symptoms and disease progression.

You may need to avoid NSAIDs or use them with caution if you have certain health conditions, such as hypertension (high blood pressure), heart disease, diabetes, a history of stomach bleeding or ulcers, or kidney problems. Some NSAIDs have blood-thinning effects, which may worsen these conditions.

Other possible side effects of NSAIDs include:

• Heartburn
• Stomach pain
• Bleeding
• Headaches
• Dizziness or lightheadedness
• Increased blood pressure
• Ringing in the ears
• Fluid buildup in the body

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

2. Oral Disease-Modifying Antirheumatic Drugs

DMARDs are medications that help slow joint damage and reduce pain and swelling. Some also help reduce psoriatic skin lesions.

DMARDs are often one of the first treatments a rheumatologist prescribes for PsA. Each one works a little differently to reduce inflammation and ease PsA symptoms.

Methotrexate

Methotrexate is the most commonly used DMARD for PsA. It interferes with how cells repair DNA, which helps prevent immune cells from multiplying. This lowers inflammation.

Methotrexate is typically taken once a week. While taking it, you’ll need regular tests to check your liver, kidney, and lung function. Methotrexate can improve both joint and skin symptoms.

This medication can be taken by mouth or as an injection under the skin. Side effects are more common when taken orally.

Most people have mild side effects that improve over time or can be managed with medications (such as anti-nausea medicine) on the day of the dose. At higher doses, side effects may include:

• Nausea or vomiting
• Hair loss
• Mouth sores
• Liver damage
• Lung problems

Leflunomide

Leflunomide is another DMARD used to treat PsA. It blocks the production of DNA building blocks, which prevents immune cells from multiplying.

Your healthcare provider may prescribe leflunomide alone or with other DMARDs. Your liver function should be checked regularly while taking this medication.

Common side effects of leflunomide include:

• Diarrhea
• Nausea
• Hair loss
• Rash
• Liver damage

Sulfasalazine

Sulfasalazine is a DMARD that contains two components — sulfapyridine (a sulfa drug) and 5-aminosalicylic acid (an anti-inflammatory drug). Researchers don’t fully understand how sulfasalazine works in PsA, but 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. Many people have fewer side effects with sulfasalazine. The most common include:

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

Cyclosporine

Originally used to prevent the immune system from rejecting organ transplants, cyclosporine can also treat PsA with severe joint inflammation or skin symptoms.

Cyclosporine is very effective and is usually used for short periods. Symptoms may start to improve within a few weeks, but full effects can take a few months.

Side effects of cyclosporine include:

• High blood pressure
• Kidney damage
• Increased risk of infection
• Increased risk of skin cancer

3. Phosphodiesterase-4 Inhibitors

Phosphodiesterase-4 (PDE4) inhibitors lower levels of cytokines (proteins that cause inflammation). The only PDE4 inhibitor approved by the U.S. Food and Drug Administration (FDA) for PsA is apremilast (Otezla).

Apremilast can be used with methotrexate, phototherapy, or topical medications. It’s often prescribed if DMARDs don’t improve symptoms or if someone can’t take biologic drugs.

Side effects of apremilast include:

• Diarrhea
• Nausea
• Headache
• Upper respiratory tract infections
• Depression or changes in mood

4. Janus Kinase Inhibitors

Janus kinase (JAK) inhibitors are a newer option for treating psoriatic arthritis. They’re usually prescribed when other treatments, such as biologics, don’t work well. Cytokines attach to JAK proteins on cells and send messages that trigger inflammation.

JAK inhibitors block these signals, helping reduce inflammation, joint pain, and swelling. Two JAK inhibitors are FDA-approved to treat PsA — tofacitinib (Xeljanz) and upadacitinib (Rinvoq).

Common side effects of JAK inhibitors include:

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

You may notice your symptoms improving within a few days or weeks of starting this daily treatment, but it can take three to six months to feel the full effects.

During treatment, your rheumatologist will order blood tests to check your blood counts, cholesterol levels, and organ function. You’ll be tested for tuberculosis each year.

In 2021, the FDA required certain JAK inhibitors, including tofacitinib and upadacitinib, to carry boxed warnings about risks such as serious heart-related events, blood clots, and cancer. If you are considering JAK inhibitors or are currently taking one, your doctor can help you understand the potential risks and benefits.

5. Tyrosine Kinase 2 Inhibitors

Tyrosine kinase 2 (TYK2) inhibitors are the newest class of oral medications for psoriatic arthritis. TYK2 is an enzyme in the same family as JAK enzymes, but it works in a more targeted way.

While JAK inhibitors block several JAK proteins, TYK2 inhibitors specifically target the TYK2 enzyme. The only TYK2 inhibitor currently FDA-approved for adults with PsA is deucravacitinib (Sotyktu).

Deucravacitinib was first approved in 2022 for moderate to severe plaque psoriasis and was approved for PsA in March 2026. It’s typically used when other treatments have not worked well enough.

Common side effects of deucravacitinib include:

• Upper respiratory tract infections
• Increased creatine phosphokinase levels
• Herpes simplex (cold sores)

Talk with your doctor about whether a TYK2 inhibitor may be right for you. Be sure to also discuss any other medications you’re taking.

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Which oral medication for PsA has worked best for you, and what side effects have you experienced? Let others know in the comments below.