DMARDs for Ankylosing Spondylitis: Key Insights
Rheumatic ConditionsAnkylosing Spondylitis

DMARDs for Ankylosing Spondylitis: What You Need to Know

DMARDs for Ankylosing Spondylitis: What You Need to Know
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Published on January 16, 2025
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Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints (those between the spine and hipbone). Less commonly, AS can affect other joints such as those in the shoulders, hips, chest wall, and knees, as well as your tendons and ligaments. Considered a type of arthritis, ankylosing spondylitis can cause various symptoms, such as:

  • Persistent pain and stiffness in the low back and buttocks
  • Reduced spinal mobility
  • Fatigue
  • Loss of appetite and weight loss
  • Pain caused by enthesitis, inflammation in the areas where tendons or ligaments attach to bones

Over time, ankylosing spondylitis can cause new bone to grow between vertebrae, eventually connecting and fusing the vertebrae together. This can significantly impair your posture and even lead to complete loss of motion in your lower back.

Managing ankylosing spondylitis effectively is crucial to minimize symptoms, maintain mobility, and prevent complications. Taken daily, nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, along with physical therapy, are usually the first steps in treating AS, helping to reduce inflammation and pain. For people with mild AS, these treatments may be all they need to manage the disease. But NSAIDs and physical therapy treat only the symptoms of ankylosing spondylitis, not the underlying cause.

If these treatments aren’t enough, disease-modifying antirheumatic drugs, or DMARDs, are the next step. These drugs, particularly a class of DMARDs called biologics, target the biological processes that cause joint inflammation and may slow disease progression, leading to fewer symptoms and less disability over time.

Understanding Biologics

Biologics are advanced DMARDs that are derived from living organisms (classic DMARDs are chemically based).

Traditional DMARDs suppress the immune system on a broad scale and are effective in reducing inflammation that affects the body’s smaller joints, such as those of the ankles, hands, and feet. But they’re not usually helpful for inflammation of the sacroiliac joint and spine.

Biologics, on the other hand, are genetically engineered antibodies or proteins designed to target specific components of the immune system that play a role in triggering inflammation in certain areas of the body. There are several biologic medications approved for ankylosing spondylitis, which differ by the inflammatory pathways they block. They are all injectable or infusible medications, unlike nonbiologic DMARDs, which can be taken orally.

Types of Biologic Treatments for Ankylosing Spondylitis

Two groups of biologic treatments have been approved for AS, and others are in development.

TNF Inhibitors

One of the main drivers of inflammation in AS is a protein called tumor necrosis factor-alpha, or TNF-alpha. TNF-alpha is a type of cytokine, a small protein that plays a large role in mediating acute and chronic inflammation by signaling the immune system to get to work.

TNF-alpha and other cytokines bind to specific receptors on cells, stimulating the production of other immune system cells — including other inflammatory cytokines — and blood cells. But TNF-alpha is overactive in people with AS, causing significant inflammation.

TNF-alpha inhibitors, also known as anti-TNF therapies, are a type of biologic that neutralize TNF by blocking its signaling pathways, reducing inflammation and joint damage. Each TNF-alpha inhibitor works in a slightly different manner, so some may work for you while others do not. Anti-TNF drugs approved for ankylosing spondylitis include:

  • Infliximab (Remicade)
  • Etanercept (Enbrel)
  • Adalimumab (Humira)
  • Certolizumab pegol (Cimzia)
  • Golimumab (Simponi)
Because TNF-alpha inhibitors dampen part of the immune system, they can increase your risk of developing potentially serious infections and decrease your ability to fight infections. They may also slightly increase your risk of certain cancers, most notably lymphoma and skin cancers.

IL-17 Inhibitors

Another major contributor to inflammation in ankylosing spondylitis is interleukin-17 (IL-17). Like TNF-alpha, IL-17 is a type of cytokine that signals specific immune cells to activate inflammation. Similar to anti-TNF drugs, IL-17 inhibitors work by binding to the protein and blocking its activity. The medications carry similar risks as TNF inhibitors, and they may additionally exacerbate or cause inflammatory bowel disease (IBD).

Two IL-17 inhibitors approved for AS, both of which target the IL-17A cytokine variety, are:

  • Secukinumab (Cosentyx)
  • Ixekizumab (Taltz)

A third IL-17 inhibitor, which inhibits both the IL-17A and IL-17F cytokine varieties, is:

  • Bimekizumab-bkzx (Bimzelx)
The FDA approved bimekizumab for AS in September 2024.

Other Emerging Biologics

Research is ongoing to develop even more effective biologic treatments. For instance, brodalumab (Siliq) is a biologic that targets IL-17 receptors, offering a new approach to reducing inflammation. Rather than blocking specific IL-17 proteins, brodalumab binds to the IL-17 receptor A (or IL-17RA) on cells, preventing various IL-17 proteins — IL-17A, IL-17F, IL-17A/F, IL-17C, and IL-17E — from doing so and starting their individual inflammatory cascades.

Brodalumab is currently approved for treating plaque psoriasis, and research suggests it’s effective for a form of arthritis called axial spondylarthritis (ankylosing spondylitis falls under the axial spondylarthritis umbrella).

Nonbiologic DMARDs

JAK Inhibitors

Janus kinase (JAK) inhibitors are a newer type of nonbiologic (synthetic) DMARD that focus on enzymes involved in immune system overactivity. These oral drugs target the JAK family of enzymes — JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2) — which play a key role in signaling cells to make dozens of different cytokines and growth factors. By inhibiting these enzymes, the drugs can effectively and simultaneously block the activity of multiple cytokines involved in immune-related rheumatic diseases, including ankylosing spondylitis.

In December 2021, the FDA approved the first JAK inhibitor for people with AS who don’t adequately respond to TNF inhibitors: tofacitinib (Xeljanz). The following year, the FDA approved another JAK inhibitor called upadacitinib (Rinvoq) for AS.

Older DMARDs

Traditional DMARDs, like sulfasalazine and methotrexate, have been used for years for inflammatory conditions. Sulfasalazine inhibits the formation of prostaglandins, a chemical that helps manage the body’s pain and inflammation, among other things. One of the ways methotrexate is believed to work is by causing cells to release adenosine, a molecule that blocks other inflammation-promoting chemicals.

For ankylosing spondylitis, however, the American College of Rheumatology recommends these DMARDs only if you meet certain conditions: You have active AS symptoms despite treatment with NSAIDs and have either considerable arthritis in your limbs or are unable to use TNF-inhibitors. When used, these DMARDS are added on to the first-line medical management with NSAIDS or biologic DMARDS. They are not used in isolation for ankylosing spondylitis. They may also be added to help treat other comorbid autoimmune conditions such as IBD or uveitis.

Choosing the Right Treatment

Organizations like the American College of Rheumatology and Spondylitis Association of America make recommendations for ankylosing spondylitis treatments to follow based on the severity of your disease, how you respond to specific medications, and whether you have comorbid conditions.

In general, their latest pharmacological guidelines, updated in 2019, recommend treatment with NSAIDs on a daily, long-term basis. If these drugs are not enough, the next type of medication to try is a TNF-inhibitor. And if that drug doesn’t work, the experts recommend switching to an IL-17 inhibitor instead of trying another anti-TNF medication.

If you don’t respond well enough to biologics, you may be prescribed a JAK inhibitor.

Like conventional DMARDs, local corticosteroid injections are only recommended in specific cases (systemic or whole-body steroids are not recommended). And all treatment plans should include regular exercise and physical therapy.

The Assessment of SpondyloArthritis International Society has similar treatment guidelines for ankylosing spondylitis.

When discussing treatment options with your healthcare provider, make sure to consider:

  • How the medication is taken (injection, IV infusion, or pills)
  • How frequently you’ll need to take pills or have injections or infusions
  • What kind of monitoring you’ll need, such as routine blood tests
  • Potential side effects and their severity
  • Cost

Questions to Ask Your Doctor

Here are a few questions to ask your rheumatologist:

  • What can I expect from my treatment?
  • What factors go into choosing which medication is right for me?
  • How long will it take to see results?
  • What side effects should I watch out for?
  • Do I need to follow a special diet?
  • Are there any special considerations if I’m planning a family or have other health conditions?
  • Are there financial assistance programs available for these medications?

The Takeaway

  • DMARDs, especially biologics and JAK inhibitors, have revolutionized the treatment of ankylosing spondylitis. They offer relief from inflammation, better mobility, and less disability.
  • Talk to your doctor about the options that best fit your needs — each type of DMARD works differently in the body, so if one medication doesn’t work, another might.
  • With the right plan, managing AS and improving your quality of life is well within reach.
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