What is the drug of choice for spondylitis?

October 7, 2025 •

3 min read

According to the Mayo Clinic, nonsteroidal anti-inflammatory drugs (NSAIDs) are the medicines most commonly used as the first-line treatment for spondylitis. However, there is no single drug that is the ultimate drug of choice for spondylitis, as treatment depends on the individual's specific condition, symptoms, and response to therapy. A combination of NSAIDs, biologics, and other therapies is often required to effectively manage the disease.

Quick Summary

Treatment for spondylitis typically begins with NSAIDs to reduce pain and inflammation. For more severe cases, especially those affecting the spine, biologics like TNF and IL-17 inhibitors are introduced. Other options, such as JAK inhibitors and conventional DMARDs, are used for non-spinal inflammation or when other drugs fail.

Key Points

NSAIDs are the initial treatment: Nonsteroidal anti-inflammatory drugs are typically the first step for managing pain and inflammation in spondylitis.
Biologics are for advanced cases: If NSAIDs fail to control symptoms, biologics like TNF or IL-17 inhibitors are introduced, particularly for severe spinal inflammation.
DMARDs target peripheral joints: Conventional DMARDs such as sulfasalazine are not effective for spinal inflammation but can help with peripheral joint involvement.
JAK inhibitors are oral alternatives: Janus kinase (JAK) inhibitors are newer oral drugs for patients who don't respond to or can't tolerate biologics.
No single 'best' drug exists: The optimal medication for spondylitis is highly individual, depending on disease severity, affected joints, and a person's response to therapy.
Medication requires close monitoring: Biologics and JAK inhibitors can increase infection risk, necessitating regular monitoring by a healthcare provider.

Ankylosing spondylitis (AS), a type of axial spondyloarthritis (axSpA), is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints. The selection of medication is a multi-step process, beginning with more general anti-inflammatory agents and progressing to highly targeted biological therapies if needed. No single 'drug of choice' exists for all patients; instead, treatment is tailored based on disease activity, affected areas, and patient response.

First-line treatment: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

For most patients with mild to moderate symptoms, NSAIDs are the first-line pharmacologic treatment. These medications work by inhibiting the body's production of prostaglandins, which are compounds that promote inflammation, pain, and fever. Unlike their occasional use for other conditions, NSAIDs are often taken daily and continuously for spondylitis to manage inflammation proactively.

Common NSAIDs prescribed for spondylitis include:

Ibuprofen (Advil, Motrin)
Naproxen (Aleve)
Indomethacin (Indocin)
Celecoxib (Celebrex), a COX-2 inhibitor that may have fewer gastrointestinal side effects than traditional NSAIDs.

NSAIDs are effective for reducing pain, stiffness, and morning stiffness. However, long-term or high-dose use carries risks of serious gastrointestinal issues, such as ulcers and bleeding, and cardiovascular problems. For some, especially those with high disease activity, NSAIDs may not provide sufficient relief alone.

Second-line treatment: Biologics

If a patient does not respond adequately to at least two different NSAIDs, or has significant spinal inflammation, biologics are typically the next step. These advanced medications are made from living cells and target specific proteins in the immune system that cause inflammation.

Tumor Necrosis Factor (TNF) Inhibitors

TNF inhibitors were the first class of biologics approved for AS and remain a common and effective option. They block the activity of tumor necrosis factor-alpha, a pro-inflammatory protein.

Examples of TNF inhibitors for spondylitis include:

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

Interleukin-17 (IL-17) Inhibitors

For patients who do not respond to TNF inhibitors, or as an alternative first-line biologic, IL-17 inhibitors may be used. They block the interleukin-17 protein, another key player in the inflammatory cascade.

Examples of IL-17 inhibitors for spondylitis include:

Secukinumab (Cosentyx)
Ixekizumab (Taltz)

Other targeted and conventional therapies

Janus Kinase (JAK) Inhibitors: These are a newer class of oral medication, often used when patients have an inadequate response to TNF inhibitors. By blocking JAK enzymes, they interfere with the signaling pathways of multiple inflammatory cytokines. Tofacitinib (Xeljanz) and Upadacitinib (Rinvoq) are examples.
Conventional DMARDs: While effective for peripheral joint inflammation, conventional DMARDs like sulfasalazine (Azulfidine) and methotrexate are not typically recommended for managing inflammation in the spine.
Corticosteroid Injections: Local injections of corticosteroids can provide quick, temporary relief for inflamed peripheral joints (like knees or shoulders) or tendon sheaths but are not used systemically for axSpA due to severe side effects with long-term use.

Comparison of Spondylitis Medications


Feature	NSAIDs	Biologics	JAK Inhibitors	Conventional DMARDs
Treatment Stage	First-line	Second-line (after NSAIDs fail)	Third-line (after biologics fail)	Reserved for peripheral joint involvement
Mechanism	Inhibits prostaglandins	Targets specific inflammatory cytokines (e.g., TNF, IL-17)	Blocks JAK signaling pathways	Broadly suppresses the immune system
Administration	Oral tablets	Injected (subcutaneous) or intravenous (IV) infusion	Oral tablets	Oral tablets
Target Area	Overall pain and inflammation (spinal & peripheral)	Specific inflammatory pathways, highly effective for spinal involvement	Multiple inflammatory pathways, effective for spinal involvement	Primarily peripheral joints, not the spine
Examples	Naproxen, Celecoxib, Indomethacin	Humira, Enbrel, Cosentyx, Taltz	Xeljanz, Rinvoq	Sulfasalazine, Methotrexate

Conclusion

In summary, while NSAIDs are the standard initial treatment for spondylitis, they are often not the final or only solution. The concept of a single 'drug of choice' is outdated given the variety of effective, targeted therapies now available. For many, a treatment regimen begins with NSAIDs and escalates to advanced biologics or JAK inhibitors if disease activity remains high or is spinal. It is crucial for patients to work closely with a rheumatologist to find the most effective medication or combination of treatments, which should always be used in conjunction with physical therapy and regular exercise. Staying informed about available treatments and your individual response is key to managing spondylitis effectively and maintaining a high quality of life.

Learn more about available treatments from the Spondylitis Association of America.

Frequently Asked Questions

The first-line medication recommended for spondylitis is nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and celecoxib.

Biologics are used when symptoms are not adequately controlled by NSAIDs alone, or if the patient has significant spinal inflammation.

No, conventional disease-modifying antirheumatic drugs (DMARDs) like sulfasalazine and methotrexate are generally not effective for spinal inflammation and are primarily used for peripheral joint symptoms.

JAK inhibitors are newer oral medications that block inflammatory signaling pathways. They are typically prescribed for patients who have not responded well to or cannot tolerate TNF inhibitors.

Corticosteroids can be effective as localized injections for temporarily relieving inflammation in specific joints. They are not recommended for systemic, long-term use due to severe side effects.

Biologics can take several months to reach their full effect. While some patients report improvement within weeks, a full response may take three to six months.

Physical therapy and consistent exercise are crucial non-pharmacological treatments that work alongside medication to help manage pain, maintain flexibility, and improve overall function.