Psoriatic arthritis (PsA) can be managed using a variety of treatment options. These include oral medications taken as pills or tablets to help control inflammation that causes joint pain, swelling, and tenderness. Some of these medications are combined with others so that they’re even more effective at relieving symptoms.

Here, we’ll discuss the four main types of oral medications for treating PsA, including when they’re used and their side effects.

1. Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically used as a first-line treatment for PsA. They’re 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. On the other hand, prescription NSAIDs are available in higher doses to treat more severe symptoms. Some people can manage their PsA using only NSAIDs, while others combine them with disease-modifying antirheumatic drugs (DMARDs) to control their symptoms.

NSAIDs work by blocking the function of specific enzymes that contribute to inflammation. Some examples of NSAIDs include:

• Aspirin
• Diclofenac (Arthrotec)
• Ibuprofen (Advil and Motrin)
• Indomethacin (Indocin)
• Meloxicam (Mobic)
• Naproxen (Aleve and Naprosyn)

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 be able to 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. DMARDs are usually among the first medications prescribed to treat PsA after using NSAIDs. If conventional DMARDs are ineffective or have too many potential side effects, your rheumatologist may recommend therapies such as biologic DMARDs. Each type of drug works slightly differently to block inflammation and relieve PsA symptoms.

Methotrexate

Methotrexate (sold as Otrexup and Trexall) 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.

Methotrexate can be combined with other DMARDs or biologics in people whose symptoms don’t improve. The most common combinations include methotrexate plus injectable therapies, including:

• Abatacept (Orencia)
• Adalimumab (Humira)
• Etanercept (Enbrel)
• Infliximab (Remicade)

Methotrexate is taken as a weekly dose, and you’ll need to have your liver function monitored while you’re on this medication.

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

Leflunomide

Leflunomide (Arava) is another DMARD used to treat PsA. However, it is prescribed off-label, meaning the U.S. Food and Drug Administration (FDA) hasn’t approved it for this use. Leflunomide prevents the production of DNA building blocks, which stops immune cells from multiplying. You may be prescribed leflunomide alone or along with other DMARDs.

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’s also an off-label treatment, and it tends to be used less often than other DMARDs.

People taking sulfasalazine tend to have fewer side effects, with the most common being headaches, nausea, or an upset stomach.

Cyclosporine

Originally used to help prevent the immune system from rejecting organ transplants, cyclosporine (Neoral) 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
• Uncontrollable shaking (tremors)

3. PDE4 Inhibitors

Phosphodiesterase-4 (PDE4) inhibitors received FDA approval within the past 10 years to treat psoriasis and PsA. This class of medications lowers levels of chemical messengers known as cytokines, which are responsible for producing inflammation. The only PDE4 inhibitor that is FDA-approved for treating PsA is Otezla, a formulation of apremilast.

According to the National Psoriasis Foundation, apremilast is often used as a second-line therapy and can be combined with methotrexate, phototherapy, or topical medications.

Side effects of apremilast include:

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

4. JAK Inhibitors

Janus kinase (JAK) inhibitors are also a relatively new option for treating psoriatic arthritis. Cytokines attach to JAK proteins on the outside of cells, which then send 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: Xeljanz (a formulation of tofacitinib) and Rinvoq (a formulation of upadacitinib).

Doctors typically prescribe JAK inhibitors for PsA for people who haven’t had adequate relief from — or can’t tolerate — certain biologic drugs. You may being to notice your symptoms improving within a few weeks of starting this daily treatment, but JAK inhibitors can take from 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 make sure 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 Xeljanz and Rinvoq, 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.

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