JAK Inhibitors Offer New Hope for Treating Ankylosing Spondylitis

People with ankylosing spondylitis responded well to a treatment previously used for rheumatoid arthritis, according to a 2020 study. Will this drug, part of a class called JAK inhibitors, become the new norm?

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What do you get when you cross joint pain with reduced mobility? You get ankylosing spondylitis (AS). And we’re not talking about the regular reduced mobility you get from creaky, painful joints caused by other forms of arthritis. It’s different with AS, because in severe cases, the bones in your spine can fuse together, literally reducing their—and your—mobility.

JAK inhibitor for ankylosing spondylitisPeople with ankylosing spondylitis may soon have new treatment options.

The disease most often starts with pain and stiffness in the back, usually after a period of inactivity. The symptoms start before age 45 and gradually develop. There is no cure for AS, but there are treatments that can improve symptoms dramatically and even put AS into remission.

Treatment of AS is most successful when started early, before irreversible damage to the joints occurs. There are successful standard treatment options available, but they don’t work for everyone. There is now promise of a new, very effective treatment with quick results – oral Janus kinase (JAK) inhibitors.

What Are JAK inhibitors?

JAK inhibitors are traditionally used to treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. The drugs work by decreasing the immune system’s activity. JAK inhibitor drugs affect several cytokines (cellular compounds) important in the development and progression of AS.

As of this publication date, only three JAK inhibitor drugs are currently available in the United States and FDA-approved to treat rheumatoid arthritis:

  • Xeljanz (tofacitinib)
  • Olumiant (baricitinib)
  • Rinvoq (upadacitinib)

Each of the approved JAK inhibitors target specific JAK enzymes.

Current Ankylosing Spondylitis Treatments

You’re not going to get a JAK inhibitor right off the bat, but it might be an option for you if first- and second-line treatments haven’t worked for you. Here’s where you’re probably going to start with your treatment:

First Line Therapies

  • NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs), specifically naproxen (Naprosyn) and indomethacin (Indocin, Tivorbex), are the medications most commonly used to treat AS symptoms of inflammation, pain and stiffness.
  • Physical therapy. Physical therapy is a key part of ankylosing spondylitis treatment and provide many benefits. A physical therapist designs specific exercises to fit individual needs, which will include:
    • Range-of-motion and stretching exercises to maintain flexibility in the joints and preserve good posture
    • Proper sleeping and walking positions, and abdominal and back exercises to maintain an upright posture
    • Strength building exercises

Second Line Therapies

If NSAIDs do not relieve symptoms, a biologic medication, may be prescribed. This class of medications includes tumor necrosis factor (TNF) blockers and interleukin-17 (IL-17) inhibitors.

  • TNF inhibitors. TNF blockers work by targeting a cell protein that is part of the immune system, TNF. (tumor necrosis alpha). TNF causes inflammation in the body, and TNF blockers suppress it.
  • IL-17 Inhibitors. IL-17 plays a role in the body's immune system defense against infection. It uses an inflammatory response to fight infections. IL-17 inhibitors help suppress the inflammatory response, thereby reducing AS symptoms.

Other Treatments

  • Surgery. Most people with ankylosing spondylitis don't need surgery. However, your doctor might recommend surgery if you have severe pain or joint damage, or if your hip joint is so damaged that it needs to be replaced.
  • Lifestyle Changes. Besides following your medical treatment plan, you can help your condition with certain lifestyle modifications:
  • Stay as active as possible to improve posture, maintain flexibility and ease pain
  • Apply heat and cold to alleviate pain, stiffness and swelling
  • Quit smoking if you are a smoker, as smoking impedes breathing in those suffering AS
  • Practice good posture

New Treatment Option: Potential Use of Oral JAK Inhibitor for Ankylosing Spondylitis

Recently, the abstract data from a large study was presented by Atul Deodhar, MD, medical director of rheumatology clinics at the Oregon Health and Science University, Portland, Oregon, at the American College of Rheumatology annual meeting.

The study is ongoing regarding the use of tofacitinib (Xeljanz) in the treatment of AS. The drug is currently in Phase 3 trials for the treatment of adults with AS. The trial results showed that patients with active AS who took tofacitinib showed improvement in fatigue, inflammation, back pain and other metrics, and that effect was significantly greater than in a placebo group.

The study enrolled 269 adults with active AS who did not tolerate at least two NSAIDS or at least two NSAIDS were ineffective at treating symptoms. Most of the participants were men with an average age of 41 and no prior exposure to biologic disease-modifying antirheumatic drugs (DMARDs).

Although adverse effects occurred more in the JAK group versus placebo group, there were no new safety risks beyond the already known adverse effects of tofacitinib. 

Will JAK inhibitors become a standard treatment?

At this point, not enough research has been conducted to make a prediction, but the data so far is promising. In the short time they’ve been studied as a treatment for AS, JAK inhibitors seem to be a safe option when used in a well-screened, well-matched patient population that includes regular monitoring.

 As with all autoimmune suppression medications, there are risks. But, JAK inhibitors appear to be as effective as other biologics, and carry the advantages of being oral and working fast. JAK inhibitor Rinvoq is in late-stage trial to treat AS, so these drugs look poised to become yet another option for people with ankylosing spondylitis.

Updated on: 02/05/21
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Robert Koval, MD
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