U ntil recently, the treatments for ankylosing spondylitis — a chronic, inflammatory type of arthritis that primarily affects the spine — have lagged behind those of other forms of arthritis. Luckily, though, things may be starting to change.
In 2021 the Food and Drug Administration (FDA) approved a new class of drugs for the treatment of ankylosing spondylitis: Janus kinase, or JAK, inhibitors.
How JAK Inhibitors Work for Ankylosing Spondylitis
7 Essential Facts About JAK Inhibitors for Ankylosing Spondylitis
1. JAK inhibitors work differently than biologics.
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.
2. JAK inhibitors have been available to treat other conditions for a decade.
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.
3. Two JAK inhibitors are approved to treat 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.
4. JAK inhibitors come in pill form.
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.
5. They start working quickly.
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.
6. They're considered safe, but have potential side effects.
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:
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.
7. Insurance or assistance programs may help cover the high cost of JAK inhibitors.
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.
Are JAK Inhibitors Right for You?
Today, JAK inhibitors are typically prescribed for use in people who have more moderate to severe ankylosing spondylitis and have tried other treatments but are still having trouble controlling the condition. Other treatment options you may need to try first include:
- NSAIDs, such as ibuprofen or COX-2 inhibitors, which are often used to treat symptoms in milder cases of ankylosing spondylitis
- Biologics, such as TNF inhibitors or IL-17 inhibitors, which are typically prescribed first to manage moderate to severe ankylosing spondylitis and prevent disease progression
For now, JAK inhibitors are third in line for treating ankylosing spondylitis. That said, “Treatment guidelines were developed before any JAK inhibitors were approved,” explains Dubreuil. The guidelines, developed by the American College of Rheumatology with the Spondylitis Association of America and Spondyloarthritis Research and Treatment Network, were released in 2015.
“They haven’t yet incorporated the JAK inhibitor data,” says Dubreuil. “It may be that in the coming years, these drugs come a little earlier in that treatment algorithm, especially as we get more data in regards to adverse events or safety.”
JAK Inhibitors for Ankylosing Spondylitis: Frequently Asked Questions
Next Steps: Making Ankylosing Spondylitis Treatment Decisions
You’ve learned a lot about JAK inhibitors for ankylosing spondylitis. So, what’s next?
Take some extra time to absorb all of this information and decide if JAK inhibitors are something you might want to consider.
Before your next appointment, think about your current treatment plan and how well it’s controlling your ankylosing spondylitis.
- Are you satisfied with your current treatment?
- Has your current treatment improved your ankylosing spondylitis symptoms as well as you had hoped?
- Are you able to follow your treatment regimen as prescribed?
- Are you downplaying any symptoms or side effects to your doctor?
- How frequently, if ever, do you cancel plans or activities because of your condition?
- Have you tried other treatments to see if they help you better manage your condition?
If you’re having trouble finding the right ankylosing spondylitis treatment plan, you might want to talk to your doctor about JAK inhibitors. Here are a few conversation starters that you can ask at your next appointment.
- Do you think it’s possible for me to gain better control of my ankylosing spondylitis?
- What else can I do to better manage my condition?
- Which medications do you recommend, and why?
- Am I a good candidate for a JAK inhibitor?
- If so, what type of results might I expect?
- How often should I monitor the progress of my treatment?