Psoriatic arthritis (PsA) treatments continue to evolve as researchers search for new therapies to better address the inflammatory disease. The latest treatment option for PsA, JAK inhibitors, shows promise for being highly effective for many people living with the condition.

JAK inhibitors, also known as Janus kinase inhibitors, are both comparatively new to medicine and to the treatment of PsA. The Food and Drug Administration (FDA) first approved tofacitinib (brand name Xeljanz) to treat PsA in 2017.

The FDA approved a second JAK inhibitor for PsA, upadacitinib (brand name Rinvoq), in December 2021.

These new medications provide targeted therapy to help prevent the immune system’s response. Studies have shown that JAK inhibitors can both reduce the severity of symptoms and slow disease progression.

For some people living with PsA, JAK inhibitors may provide more effective relief to their symptoms compared to other treatment options, such as biologics and steroid injections.

The immune system operates using several different pathways or connections. These pathways allow the body to signal the immune system to activate and attack threats within the body.

People living with PsA or other rheumatic diseases make too much of a protein called cytokines. Cytokines attach to receptors on immune cells and signal the immune system to respond, causing inflammation and swelling.

JAK inhibitors are oral pills that work by interfering with the signaling pathways. The small molecules within the medication attach to the immune cells, which effectively stop the cytokines from activating an immune response.

As a result, symptoms of PsA lessen or go away and the disease doesn’t progress as quickly or cause additional damage to the joints or body.

JAK inhibitors have performed well in clinical trials, which indicates that, in general, they are safe and effective for treating PsA in many people.

Some studies have compared the use of JAK inhibitors to other PsA treatments.

In a 2021 study, researchers compared JAK inhibitors to biologic disease-modifying antirheumatic drugs (DMARDs). They found that people who had an unfavorable reaction to at least one biologic responded well to upadacitinib, the most recently approved JAK inhibitor.

In a 2020 study, researchers noted the overall effectiveness of JAK inhibitors. They stated that administering corticosteroids into the circulatory system is rarely recommended for PsA treatment. They also noted that synthetic versions of DMARDs, such as methotrexate, provide less effective therapy and typically get prescribed due to low cost.

Doctors often prescribe methotrexate, a systemic DMARD, as a first-line treatment for PsA. However, research indicates that this medication has a high rate of toxicity and may not be effective for PsA.

Though future research may show different findings, researchers generally believe JAK inhibitors are at least as effective as biologics and superior to methotrexate in treating PsA.

Currently, doctors tend to prescribe methotrexate as a first therapy for PsA. Though its effectiveness is not proven, its cost is low. The average dose falls between 5 and 25 milligrams.

Evidence suggests that JAK inhibitors may be a cost-effective treatment option for PsA. In a 2020 study, researchers estimated that using tofacitinib as part of advanced therapy for PsA saved over $8 million combined for 1 million insured people over the course of 2 years.

The approved dose of upadacitinib for treating PsA is 15 milligrams a day.

An important distinction between JAK inhibitors and biologics is how doctors administer them. Doctors have to use infusions in the office or prescribe injections to give biologics whereas a person can take JAK inhibitors in pill form.

A person may need to take JAK inhibitors daily. Biologics may only need administration once a week or every few weeks, though dosing can vary based on what the doctor prescribes.

JAK inhibitors can cause side effects.

Some of the most common side effects associated with JAK inhibitors include:

  • diarrhea
  • nausea
  • headaches
  • increased cholesterol levels
  • indigestion
  • upper respiratory tract infection

Less commonly, they may also cause serious side effects, such as:

  • increased risk of bowel perforation
  • abnormal liver function tests
  • infection
  • abnormal blood counts
  • decrease in kidney function

Biologics can also cause side effects. They can relate both to the medication itself and to the injection sites. Some common and potential side effects associated with biologics include:

  • injection site reactions, such as redness and swelling
  • reaction to the infusion including headaches, swelling, trouble breathing, flushing, fever, chills, chest pain, rash, pain, high or low blood pressure, and anaphylaxis
  • increased risk of infection
  • headaches
  • nausea

Methotrexate can cause side effects including:

  • nausea
  • vomiting
  • lightheadedness
  • stomach cramping
  • depression
  • soreness at the injection site

In some cases, it can lead to toxicity, though this is relatively rare.

JAK inhibitors are a new form of treatment used in managing PsA. Studies have shown they are generally safe and effective for use in most people, and they may present as a good alternative to biologics and other forms of PsA treatment.

Consider speaking with your doctor about JAK inhibitors if you are living with moderate to severe PsA, as they may be a helpful and cost-effective form of treatment.