• If nonsteroidal anti-inflammatory drugs (NSAIDs) aren’t working to control your ankylosing spondylitis (AS), more advanced treatments are an option.
• Janus kinase (JAK) inhibitors and biologics can help treat symptoms and slow the progression of AS.
• In rare cases of advanced AS, surgery may be appropriate.

Ankylosing spondylitis is a disorder in which the immune system mistakenly attacks healthy tissue in the spine, causing inflammation, pain, and joint damage. As the disease progresses, joints can become so damaged that they cause ankylosis — formation of new bone. Ankylosis fuses the joints together and limits movement. AS is also referred to as radiographic axial spondyloarthritis or radiographic axSpA.

Treatment goals for AS include relieving symptoms, maintaining or improving physical function, minimizing AS complications, and slowing the progression of the disease. The right treatment for you will depend on your symptoms and other signs of your condition. Throughout your journey with AS, you may need to switch from the initial medications your doctor prescribed to advanced treatments.

First-Line Treatments

Nonsteroidal anti-inflammatory drugs are the first line of treatment for AS symptoms like back pain or uveitis (eye inflammation). NSAIDs include common over-the-counter medications such as ibuprofen (Advil) and naproxen (Aleve), as well as prescription drugs like indomethacin (Indocin) and diclofenac (Voltaren). NSAIDs ease pain and reduce inflammation.

People with AS are sometimes prescribed corticosteroids to relieve inflammation, but long-term use of corticosteroids is not recommended. Older disease-modifying antirheumatic drugs (DMARDs) like methotrexate (Otrexup) and sulfasalazine (Azulfidine) are sometimes prescribed to treat AS, although these drugs are generally not a preferred option. Physical therapy can also help increase strength and flexibility in the spine, hips, or other problem areas.

NSAIDs aren’t always enough to manage symptoms and keep AS from progressing. If that’s the case, your doctor may recommend more advanced treatments. Advanced treatments for AS usually include newer classes of drugs, such as biologics or Janus kinase (JAK) inhibitors. Talk to your rheumatologist if your current treatment plan is not sufficiently controlling your pain and other symptoms. Your doctor can help you understand if it’s time to switch AS treatments.

1. TNF Inhibitors

Biologic drugs work to reduce inflammation and slow the progression of AS. Biologic drugs for AS and other forms of inflammatory arthritis, such as rheumatoid arthritis or psoriatic arthritis, may also be referred to as biologic DMARDs. These medications use bioengineered molecules to target specific parts of the immune system that cause inflammation.

The most common biologic treatments for AS are tumor necrosis factor (TNF)-alpha inhibitors. TNF-alpha inhibitors block a chemical in the body called tumor necrosis factor, which causes inflammation. Taking a TNF-alpha inhibitor reduces the inflammation caused by AS and halts disease activity, slowing the progress of joint damage and other symptoms of AS.

TNF-alpha inhibitors include:

• Adalimumab (Humira)
• Certolizumab pegol (Cimzia)​​​​​​
• Etanercept (Enbrel)
• Golimumab (Simponi)
• Infliximab (Remicade)

These drugs are given either through self-injection or injections given in a health care provider’s office. The injections are usually taken every few weeks.

Side effects of TNF-alpha inhibitors include an increased risk of infection, skin reactions near the site of the injection, and rare neurological complications. TNF-alpha inhibitors might increase the risk of some types of cancer, such as lymphoma and nonmelanoma skin cancer. An annual skin examination is essential if you take a TNF-alpha inhibitor.

Because of the increased risk of infection, people who want to take TNF-alpha inhibitors should be tested for tuberculosis before starting the medication. In addition, people with multiple sclerosis or significant heart failure should not use TNF inhibitors.

2. Interleukin Inhibitors

Like TNF-alpha inhibitors, interleukin (IL) inhibitors are biologic drugs. They treat AS by blocking different types of molecules called interleukins that cause inflammation.

IL inhibitors for AS block IL-17, a chemical that triggers the immune system to produce inflammation around the body. IL-17 inhibitors include secukinumab (Cosentyx) and ixekizumab (Taltz). These medications slow inflammation and limit tissue damage caused by an overactive immune system. They are also given through an injection under the skin.

IL-17 inhibitors have similar side effects as TNF inhibitors. They can also raise the risk of infection, including colds, diarrhea, and urinary tract infections. People interested in taking IL-17 inhibitors should talk to their doctor if they currently have tuberculosis or have had this infection in the past. Additionally, because these drugs can restrict the immune system, people using them may need to take precautions before receiving vaccines that contain live viruses.

These medications can also cause or worsen inflammatory bowel disease such as ulcerative colitis or Crohn’s disease. Watch for symptoms, including severe abdominal pain, rectal bleeding, or ongoing diarrhea.

3. JAK Inhibitors

Janus kinases are proteins that act as signals from cells to other proteins. They are small, lab-designed molecules designed to “turn off” the JAK signaling that produces inflammatory chemicals. Because they target very specific proteins, JAK inhibitors may be easier to tolerate than TNF-alpha inhibitors.

There are three types of Janus kinases: JAK1, JAK2, and JAK3. Janus kinases respond to cytokines, small proteins involved in cell signaling. When cytokines attach to a cell, JAK proteins “turn on” and tell cells to make more cytokines, producing inflammation. Normally, this inflammation is actually healthy — it’s used to kill harmful viruses and bacteria. However, if you have AS, JAK signaling doesn’t shut off when it should.

A JAK inhibitor may be an option if biologic drugs don’t work for you, or have stopped working. Two JAK inhibitors are currently approved by the U.S. Food and Drug Administration (FDA) to treat AS. Recent studies have found them useful in treating AS symptoms and slowing the progression of the disease. Unlike biologic drugs that are injected, JAK inhibitors are taken orally.

Tofacitinib (Xeljanz) and upadacitinib (Rinvoq) are JAK inhibitors currently available as treatments for AS. In a 2020 study of 269 people with AS, 41 percent of those taking tofacitinib had improved inflammation and pain levels after 16 weeks, compared to only 13 percent of people taking a placebo. A clinical trial of 187 people taking upadacitinib showed that 52 percent of people with AS had improvements in pain and inflammation.

Xeljanz targets all three JAK proteins and Rinvoq inhibits the JAK1 protein.

Like TNF-alpha inhibitors, JAK inhibitors can raise your risk of infection and your risk for certain types of cancer. They may cause mild side effects such as nausea, headaches, diarrhea, or high cholesterol levels. Rarely, these medications could affect your liver or kidney function. In addition, JAK inhibitors can be a risk factor for blood clots.

4. Surgery

When other treatments do not relieve severe AS symptoms, spinal surgery may be appropriate. Advanced symptoms of AS that may require surgery include kyphosis (curvature of the spine), neuropathy (nerve damage leading to tingling, pain, or numbness), spinal instability, and severe hip joint problems.

The type of surgery used depends on what specific problems are causing symptoms. Spinal surgeries to treat AS include:

• Laminectomy (decompression) — A procedure to remove part of the bone tissue in the vertebra (small bone that makes up the spine) to relieve pressure in the spine
• Osteotomy — A type of surgery in which fused vertebrae are separated
• Spinal fusion — A procedure that connects two or more vertebrae to stabilize the spine

Read more about surgery for ankylosing spondylitis.

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