The treatment of Ankylosing Spondylitis (AS) focuses on reducing inflammation, relieving pain, and slowing the progression of the disease.
Below is a detailed list of medications commonly used for managing Ankylosing Spondylitis:
1. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
NSAIDs are typically the first-line treatment for reducing pain and inflammation in AS. NSAIDs are the most commonly used class of medication for the treatment of pain and stiffness associated with spondyloarthritis. Ibuprofen, for instance, is a generic NSAID and is found in over-the-counter pain relievers such as Advil and Motrin.
Sometimes, high doses of NSAIDs are needed to maintain relief from the symptoms of ankylosing spondylitis and related diseases. This can pose a problem because NSAIDs can cause significant side effects, especially in the gastrointestinal tract (stomach, intestines, etc.). NSAIDs can cause reduced amounts of protective mucus in the stomach, which can result in stomach irritation. Over time, this can lead to heartburn, gastritis, and possibly ulcers and even bleeding. People can take other medications (such as antacids) to neutralize or prevent the production of excess stomach acid, help coat and protect the stomach (such as Carafate), or restore the lost mucus (such as Cytotec).
There may also be an increased risk of heart attack or stroke associated with NSAIDs, especially in people with a history of heart diseases.
A different class of NSAIDs known as COX-2 inhibitors (or COXIBs) seem to reduce the risk of gastrointestinal complications associated with traditional NSAID therapy. Celebrex (Celecoxib) is still being used to treat spondyloarthritis. Others, such as Vioxx, were pulled from the market in 2004 because of the high rate of heart attacks caused by the drug.
- Ibuprofen (e.g., Advil, Motrin)
- Naproxen (e.g., Aleve)
- Diclofenac (e.g., Voltaren)
- Indomethacin (e.g., Indocin)
- Meloxicam (e.g., Mobic)
- Celecoxib (e.g., Celebrex) – A COX-2 inhibitor with fewer gastrointestinal side effects than traditional NSAIDs.
2. Disease-Modifying Antirheumatic Drugs (DMARDs)
DMARDs are used to treat joint inflammation, particularly in areas other than the spine (e.g., knees, hips). Janus kinase (JAK) inhibitors, also known as JAKi, are the latest class of synthetic (non-biologic) disease-modifying anti-rheumatic drugs (DMARDs) that have been proven effective in the treatment of multiple forms of arthritis, including psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA). These medications are taken orally as pills, as opposed to biologics, which are injectable.
JAK inhibitors specifically target the JAK family of enzymes, namely JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), each of which are involved in the initiation of the signal for a cell to make more than 60 different cytokines and growth factors.
Unlike biologics, which inhibit the effects of one single cytokine, JAKi can block the effects of multiple cytokines that are implicated in the pathogenesis (development) of many immune-mediated rheumatic diseases, including AS. They have a shorter half-life compared to biologics, meaning they are active in the body for less time, which means if they are discontinued, any side effects will disappear in a quicker fashion.
Two JAKi are FDA-approved for ankylosing spondylitis (AS) and for psoriatic arthritis (PsA): tofacitinib (Xeljanz or Xeljanz XR) and upadacitinib (Rinvoq). Upadacitinib is also approved for non-radiographic axial spondyloarthritis (nr-axSpA).
They may not be as effective for axial (spinal) symptoms of AS but can be helpful for peripheral joint involvement.
- Sulfasalazine (e.g., Azulfidine)
- Methotrexate (e.g., Rheumatrex, Trexall)
- Leflunomide (e.g., Arava)
3. Biologic Medications
Biologics are highly effective for treating moderate to severe AS, especially when NSAIDs are not sufficient. They target specific proteins in the immune system that drive inflammation.
TNF Inhibitors (Anti-TNF Medications):
- Adalimumab (e.g., Humira)
- Etanercept (e.g., Enbrel)
- Infliximab (e.g., Remicade)
- Golimumab (e.g., Simponi)
- Certolizumab (e.g., Cimzia)
IL-17 Inhibitors: IL-17 inhibitors are another class of biologic medications approved for spondyloarthritis. There are currently three IL-17 inhibitors approved by the FDA for forms of spondyloarthritis – specifically for ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), and psoriatic arthritis (PsA). Cosentyx (secukinumab) was approved for AS and PsA in January of 2016, and Taltz (ixekizumab) was approved for PsA in December of 2017, and for AS in August of 2019. Both were approved for nr-axSpA in June of 2020. In September of 2024, Bimzelx (bimekizumab-bkzx) was approved for active PSA, active nr-axSpA with objective signs of inflammation, and active AS.
Both IL-17 and TNF-α are inflammatory cytokines (cell signaling molecules) that, as the name implies, signal to activate inflammation throughout the body, modulating or altering the immune system response. Inflammatory cytokines play an important role; however, when there is an overabundance of these, as has been described in inflammatory disease, they can cause harm to the body if left unchecked.
IL-17 and TNF-α cytokines signal to specific immune cells directing them to activate inflammation, with each cytokine being responsible for signaling to a different set of cells. IL-17 and TNF inhibitor medications work by targeting their respective cytokines, obstructing their signaling pathways, and by this mechanism seek to reduce inflammation. Since IL-17 inhibitors target different cytokines than the TNF inhibitors, the hope is that this newer class of biologic medications will help those who haven’t responded well to the TNF inhibitors, or are not able to tolerate them.
Bimzelx is currently the first and only inhibitor of both IL-17A & IL-17F approved to treat chronic immune-mediated inflammatory diseases, providing another variation of biologic that may help those who haven’t responded well to others.
IL-17 inhibitors carry similar risks of infections, and reduced ability to fight infections as the TNF inhibitors. They have also shown in clinical trials to exacerbate inflammatory bowel disease in patients who have it, as well as bring on new cases of inflammatory bowel disease.
- Secukinumab (e.g., Cosentyx)
- Ixekizumab (e.g., Taltz)
IL 12/23 Inhibitor
Ustekinumab (Stelara) works similarly to the IL-17 inhibitor, but targets different cytokines: IL-12 and IL-23. Stelara was approved in 2013 for psoriatic arthritis. Stelara also carries increased risks of infections, and reduced ability to fight infections, as well as a slightly increased risk of certain cancers.
4. Corticosteroids
Corticosteroids are used for short-term relief during flare-ups. They may be injected directly into inflamed joints or taken orally for systemic inflammation.
- Prednisone (e.g., Deltasone)
- Triamcinolone (e.g., Kenalog) – Typically used in joint injections.
5. Pain Relievers (Analgesics)
When NSAIDs are insufficient or not recommended, pain relievers may be used.
- Acetaminophen (e.g., Tylenol) – Offers pain relief but does not reduce inflammation.
- Opioids (e.g., tramadol, codeine) – For severe pain, used only short-term due to the risk of dependence.
6. Muscle Relaxants
Muscle relaxants may be prescribed to alleviate muscle spasms and stiffness.
- Cyclobenzaprine (e.g., Flexeril)
- Methocarbamol (e.g., Robaxin)
7. Topical Analgesics
Topical treatments may be applied directly to the skin over affected joints to reduce localized pain.
- Diclofenac gel (e.g., Voltaren Gel)
- Capsaicin cream (e.g., Zostrix)
8. Janus Kinase (JAK) Inhibitors
JAK inhibitors are newer oral medications that can reduce inflammation and are being explored for treating AS.
- Tofacitinib (e.g., Xeljanz) – Primarily approved for other forms of arthritis, but under investigation for AS.
9. Lifestyle Modifications and Physical Therapy
While not medications, exercise, physical therapy, and posture training are essential for maintaining flexibility and mobility in AS patients.
Important Considerations:
- Monitoring: Regular follow-up with a healthcare provider is crucial for monitoring disease activity and potential medication side effects.
- Combination Therapy: A combination of medications (e.g., NSAIDs with biologics) may be used for optimal management of AS.
- Tailored Treatment: Not all patients respond the same way to medications, and treatment plans should be individualized based on the severity of the disease, comorbidities, and patient preferences.
By using a combination of medications and lifestyle changes, most individuals with Ankylosing Spondylitis can achieve significant relief from symptoms and prevent disease progression.
Pain Medications, Pain Relief, and Pain Management
