The Consumer’s Guide to JAK Inhibitors for Ankylosing Spondylitis

Both biologics and JAK inhibitors work on the immune system, but they do so in different ways, says Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology in Houston.

Biologics work by suppressing one target in the immune response pathway — specifically, a single cytokine, which is a cell-signaling molecule thought to be involved in ankylosing spondylitis. Different biologics target different cytokines, so if one biologic isn’t effective, you could switch to another biologic, which may better treat the condition.

JAK inhibitors suppress various targets in the body to prevent the overactive immune response before it starts. The medications target a number of enzymes, suppressing over 60 different cytokines and other growth factors. This disrupts the communication in the immune response pathway and helps regulate inflammation before it becomes overactive, which helps suppress symptoms of ankylosing spondylitis and control the disease.

JAK inhibitors first came on the market in 2012, when they were used to treat rheumatoid arthritis (RA). But beginning in 2021, the FDA began to approve the drugs for other conditions, including psoriatic arthritis and ankylosing spondylitis.

The current FDA-approved approved options for ankylosing spondylitis include:

• tofacitinib (Xeljanz or Xeljanz XR)
• upadacitinib (Rinvoq)

“Hopefully, we’ll have a third potentially approved in coming years in that same class, and we’ll gain an even stronger foothold in the treatment of ankylosing spondylitis,” says Maureen Dubreuil, MD, a rheumatologist specializing in spondyloarthritis at Boston University School of Medicine.

Whereas biologic drugs are administered via injection or infusion, JAK inhibitors are oral medications.

“Having this treatment available as an approved option helps a lot of patients who want an oral option or who may have contraindications to the other drugs that are used [for more moderate to severe disease],” says Dr. Bose.

You may start to notice improvements in your condition quickly — as soon as two weeks after starting on a JAK inhibitor — although it may take up to six months to achieve maximum benefit.

In clinical trials, both tofacitinib and upadacitinib were shown to be safe and effective for treating ankylosing spondylitis.

Results from a study published in February 2022 in the German journal Zeitschrift für Rheumatologie found that three JAK inhibitors (including tofacitinib and upadacitinib) were proven to be safe and effective in people with ankylosing spondylitis who experienced an insufficient response or intolerance to two or more NSAIDs.

There are potential side effects, though. The FDA has recently issued an updated black box warning on JAK inhibitors, noting an increased risk of cancer and serious heart problems, including blood clots, heart attack, and stroke — even death.

While this sounds alarming, it’s not necessarily a reason to avoid JAK inhibitors. “The information we have available is largely from other diseases — rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease,” explains Dr. Dubreuil, and in the future, doctors will have more data to confirm the findings or refute them.

“Hopefully, we’ll be able to say these may be a little more safe in some people than others,” says Dubreuil.

JAK inhibitors also come with a risk of side effects, including:

• Infection
• Nausea
• Diarrhea
• Headaches

Though less common, these medications may also lead to abnormal blood counts or liver function test results, decreased kidney function, or increased risk of bowel perforation. That’s why, when taking a JAK inhibitor, it’s important to check in with your doctor regularly to monitor how you’re doing.

The good news? JAK inhibitors have a short half-life, meaning if you need to stop taking them due to any side effects, things should improve quickly.

JAK inhibitors are an expensive treatment option that can cost upward of $60,000 a year. While insurance often covers most of the cost, you may need to try other medications first before that coverage kicks in.

“Right now, many health insurance companies require that doctors recommend or try medications in a certain order, because some of the options are quite costly,” explains Dubreuil. As such, you may need to try NSAIDs and biologics first — to see if they’re able to help you gain control of your disease — before moving on to JAK inhibitors.

If you wish to try JAK inhibitors earlier on, it’s important “to think about how much you might be willing to pay out of pocket,” adds Dubreuil. Your individual expenses will vary based on your health insurance coverage.

You can also reach out to the drug company directly to see if you qualify for their patient assistance programs, which help cover your out-of-pocket drug costs.