Biologics for Ankylosing Spondylitis: How They Work

Biologics control ankylosing spondylitis by blocking specific proteins that trigger chronic inflammation. These biologic drugs target cytokines (proteins that regulate the immune response) associated with inflammation in your spine and joints. This targeted action can reduce inflammation, relieve pain and stiffness, and limit long-term joint damage.

At Total Orthopedics & Sports Medicine, our specialists assess your symptoms, spinal inflammation, and response to current treatment. We then develop a personalized care plan that may combine biologic therapy with other nonsurgical options. We also schedule regular follow-up visits to track your response and adjust your treatment when needed. Call 855-321-6784 to book an appointment.

How Do Biologics Treat Ankylosing Spondylitis?

Biological treatment reduces excessive immune activity that triggers inflammation around your spine and joints. These medicines target a specific cytokine pathway that contributes to the inflammatory response. As this immune activity decreases, cytokines (immune signaling proteins) send fewer inflammatory signals to affected tissues. This change can ease pain and stiffness, improve mobility, and lower overall disease activity.

In fact, the ATLAS clinical trial studied 315 patients with active ankylosing spondylitis who received adalimumab or a placebo. After 12 weeks, 58.2% of patients who received adalimumab achieved at least 20% improvement, compared with 20.6% in the placebo group. Researchers also found at least a 50% reduction in disease activity among 45.2% of patients who received adalimumab. In comparison, only 15.9% of patients in the placebo group reached this level of improvement.

Similarly, a phase III study published in the Annals of the Rheumatic Diseases evaluated secukinumab in 371 patients with active ankylosing spondylitis. After 16 weeks, patients who received secukinumab showed greater improvements in disease activity, physical function, and quality of life than those who received a placebo. These improvements continued through 52 weeks of treatment.

What Do Biologics Target In Your Immune System?

Biologics target specific components of the immune system, such as inflammatory proteins, immune cells, and chemical signals. For ankylosing spondylitis, these biologic drugs primarily block cytokines (immune signaling proteins) such as tumor necrosis factor-alpha and interleukin-17 (IL-17). This targeted action interrupts a specific cytokine pathway linked to inflammation.

Other biological therapies can act on B cells or T cells in certain forms of inflammatory arthritis. B-cell therapies target immune cells that can produce harmful antibodies, while T-cell therapies limit abnormal immune cell activation. However, these cell-targeted treatments are not standard biologic options for ankylosing spondylitis.

Here are the two common types of biologics used for ankylosing spondylitis:

• TNF-Alpha Inhibitors: Target TNF-alpha linked to spinal inflammation.
• IL-17 Inhibitors: Focus on IL-17 linked to disease activity.

How Do TNF Inhibitors Reduce Spinal Inflammation?

TNF inhibitors target tumor necrosis factor alpha, a protein that promotes inflammation in your spine. When your immune system releases too much TNF-alpha, inflammation can increase around the spinal joints and ligaments. Over time, this inflammation can contribute to pain, stiffness, and limited movement. These medicines prevent TNF-alpha from sending inflammatory signals to immune cells.

As these signals decrease, the inflammatory process becomes less active. This effect can reduce morning stiffness and pain while improving spinal mobility. Doctors often choose this class as an initial biologic treatment for active ankylosing spondylitis. For example, your treatment plan may use one of the following five TNF inhibitors approved for ankylosing spondylitis:

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

These medicines can reduce inflammation across the spine and joints and improve related symptoms. Some TNF inhibitors can also control inflammation linked to uveitis (eye inflammation) or inflammatory bowel disease. However, they do not cure ankylosing spondylitis or reverse structural changes that already exist. Instead, treatment focuses on controlling active inflammation and improving daily function.

What Makes IL-17 Inhibitors Different From TNF Inhibitors?

TNF inhibitors target tumor necrosis factor alpha, which contributes to inflammation throughout the body. In contrast, IL-17 inhibitors target interleukin-17, an immune messenger linked to joint, spinal, and skin inflammation. However, IL-17 inhibitors may worsen inflammatory bowel disease, so doctors use them with caution.

While both biologics can control active ankylosing spondylitis, they differ in their related conditions and clinical use, such as:

Difference	IL-17 Inhibitors	TNF Inhibitors
Main target	Interleukin-17 (IL-17)	Tumor necrosis factor alpha (TNF-α)
Common options	Secukinumab, ixekizumab	Adalimumab, etanercept
Related conditions	Often considered with plaque psoriasis	Certain TNF inhibitors may suit IBD or recurrent uveitis
Clinical history	Newer biologic class	Longer history of clinical use
Key safety concern	Infection risk; caution with IBD	Infection risk, including tuberculosis

Moreover, a 2025 study published in Arthritis Research & Therapy compared TNF and IL-17 inhibitors in 148 patients who had previously used biologics. After three years, 78.5% of patients continued TNF inhibitors. In comparison, 62.5% continued IL-17 inhibitors.

However, the type of biologic alone did not significantly affect the chance of stopping treatment. Patients who had already tried more biologics had a higher chance of stopping their current treatment. Higher disease activity also increased the chance of treatment discontinuation.

When Are Biologics Recommended For Ankylosing Spondylitis?

Biologics are recommended when nonsteroidal anti-inflammatory drugs and other first-line treatments do not provide enough relief from active ankylosing spondylitis. Doctors usually recommend them after you have tried at least two different NSAIDs for an adequate period without enough improvement. Unlike traditional medications, biologics target specific pathways that drive inflammation.

Doctors may also recommend biologic treatment in the following cases:

1. Limited Daily Function

Persistent symptoms can interfere with work, sleep, exercise, and everyday tasks. Pain and stiffness may also limit your ability to move comfortably throughout the day. At this point, your doctor may recommend biologics to achieve better disease control. Their therapeutic benefits can reduce symptoms and improve daily function.

2. Active Disease on Imaging

MRI may show active inflammation around the sacroiliac joints or spine. These changes can confirm that ankylosing spondylitis is still active despite initial treatment. Imaging may also show structural changes that require closer disease control. Your doctor will compare these findings with your symptoms before recommending biologic treatment.

Which Biologic Treatment Is Best For Ankylosing Spondylitis?

Tumor necrosis factor inhibitors are often the first biologic recommended for active ankylosing spondylitis. These different biological agents target TNF-alpha to reduce spinal inflammation, pain, and joint stiffness. In fact, a meta-analysis published in BioMed Research International found that TNF-alpha inhibitors significantly controlled disease activity.

In particular, infliximab and other TNF monoclonal antibodies had a ranking score of 77.4% for reducing disease activity. Moreover, the researchers noted that TNF-alpha inhibitors, especially infliximab, could be a first-line choice for patients with rapid disease progression. The study also found promising results for bimekizumab, which targets both IL-17A and IL-17F.

However, in clinical practice, your doctor will review the following factors before recommending a biologic:

• Symptoms: The location and severity of your symptoms can guide treatment.
• Other Conditions: Psoriasis, uveitis, or inflammatory bowel disease can affect the choice.
• Previous Treatment: Your response to prior medications can guide your next option.
• Treatment Method: Some biologics are administered via subcutaneous injection, whereas infliximab requires intravenous infusion.
• Lifestyle: Treatment frequency and convenience can affect which option works with your routine.

Are Biologics Given As Injections Or Infusions?

Biologics are given as injections or infusions because they contain large, complex molecules. Stomach acid can break these molecules down before they reach the bloodstream. For this reason, injections and infusions deliver the medicine without passing through the digestive system.

Depending on the biologic dose, you may receive treatment at home or in a healthcare setting. For example, subcutaneous injections can often be self-administered at home. In contrast, intravenous infusions require a healthcare professional and usually take place at a clinic or infusion center.

Note: You should alternate injection sites regularly to reduce skin irritation and minimize scarring.

How Do Biologics Differ From Traditional Drugs?

Biologics are large, complex medicines produced from living cells or organisms. These genetically engineered proteins can be produced inside bacteria, yeast, or animal cells. Their production requires carefully controlled conditions because small changes can affect the final medicine. In contrast, traditional drugs are small molecules created through chemical reactions in a laboratory.

While both types of medicine can relieve symptoms and treat disease, they differ in the following ways:

Difference	Biologics	Traditional Drugs
How They Work	Target specific proteins or immune pathways	Often act on broader targets such as enzymes or receptors
How They Are Given	Usually given by injection or IV infusion	Often taken as pills, capsules, or liquids
Copies	Have highly similar versions called biosimilars	Can have chemically identical generic versions

Quick Note: Monoclonal antibodies are a common form of biologics. They are designed to recognize and target specific proteins involved in inflammation.

What Tests Do You Need Before Starting A Biologic?

Before starting biologic medications, your doctor will usually screen for tuberculosis (TB), hepatitis B, and hepatitis C. They may also order a complete blood count (CBC) and liver and kidney tests. Along with these tests, CRP and ESR can identify an inflammatory condition and support your overall ankylosing spondylitis diagnosis. Here is how these tests prepare you for safe use of advanced therapies:

• Tuberculosis Screening: An IGRA blood test, a skin test, or a chest X-ray can detect active or latent tuberculosis.
• Hepatitis Screening: Blood tests check for hepatitis B and hepatitis C, which some biologics can reactivate.
• Complete Blood Count: A CBC checks red blood cells, white blood cells, and platelets for abnormal levels.
• Liver and Kidney Tests: These tests check how well your liver and kidneys function before biologic treatment.
• Inflammatory Markers: CRP and ESR measure inflammation and provide baseline values for future comparison.

How Can You Tell If Your Biologic Is Working?

Biologic treatment is effective when your symptoms decrease, and daily activities become easier. As the treatment controls inflammation, you may notice less pain, stiffness, and fatigue. These changes are important patient-reported outcomes that show your response to treatment.

Lower CRP levels can further support the treatment’s clinical efficacy. However, the time needed to notice these improvements can vary between biologics. For example, your treatment response may progress over several months, based on the following estimated timeline:

• First Few Weeks: You may notice small improvements after the first few doses.
• 3 to 4 Months: Symptoms and daily function may improve more noticeably.
• Up to 6 Months: Some biologics may take up to 6 months to reach their full effect.

Important Note: You should track your symptoms, pain levels, and daily activities throughout biologic treatment.

What Happens If Your First Biologic Does Not Work?

If your first biologic does not provide enough relief, your doctor may recommend another treatment option. They may first switch you to a different biologic within the same class, such as another TNF inhibitor. If that approach does not control inflammation, they may recommend a different class, such as an IL-17 inhibitor.

Moreover, your doctor may recommend other targeted therapies to manage symptoms of ankylosing spondylitis, such as:

1. JAK Inhibitors

JAK inhibitors are targeted, synthetic disease-modifying antirheumatic drugs (DMARDs) that reduce inflammatory signals inside immune cells. Unlike biologics, these medicines come as tablets for oral administration. Your doctor may recommend them when TNF inhibitors do not provide enough relief or cause side effects.

According to the Spondylitis Association of America, JAK inhibitors such as tofacitinib and upadacitinib have shown benefits for ankylosing spondylitis. In one trial, 56% of patients who received tofacitinib achieved at least a 20% improvement after 16 weeks, compared with 29% of patients who received a placebo. However, your doctor will review the potential adverse effects before recommending this treatment.

2. Supportive Treatment

Your doctor may adjust other treatments while you wait for a new medication to take effect. During this period, anti-inflammatory drugs (NSAIDs) can provide temporary relief from pain and stiffness. This added support can manage symptoms while your doctor monitors your response.

Along with medication, guided exercises can improve spinal mobility, posture, and muscle strength. Low-impact activities such as walking, swimming, and cycling can further support joint movement. Regular stretching and deep-breathing exercises can also improve posture and chest mobility. Moreover, your doctor may recommend the following lifestyle adjustments to support mobility:

• Posture: Practice proper alignment while sitting and standing.
• Workplace Ergonomics: Use supportive seating to reduce strain during desk work.
• Sleep Setup: Choose a supportive mattress and pillow that promote neutral spinal alignment.
• Smoking: Avoid smoking, since it is associated with worse outcomes in ankylosing spondylitis.

Can You Stop Biologics When Your Symptoms Improve?

No, you should not stop biologic treatment on your own when your symptoms improve. These medicines continue to treat inflammation even when pain and stiffness are well controlled. Without treatment, inflammation can become active again and cause symptoms to return.

However, your doctor may gradually reduce the dose or extend the time between doses after sustained remission. This approach, called tapering, requires close medical supervision to monitor for inflammation. In fact, a systematic review published in International Immunopharmacology examined biologic tapering in axial spondyloarthritis.

Researchers reviewed 14 studies published between 2008 and 2020. Across these studies, 20.2% to 93.7% of patients maintained remission after a gradual reduction in anti-TNF treatment. However, complete discontinuation carried a high risk of disease flares.

What If Ankylosing Spondylitis Has Damaged Your Spine?

Long-term inflammation can trigger abnormal bone formation that gradually changes the structure of your spine. Over time, this new bone can fuse nearby vertebrae and reduce spinal flexibility. As this fusion progresses, your spine can become more rigid and limit your range of motion. Without proper disease control, these structural changes may lead to complications such as:

• Kyphosis: A permanent forward curve of the upper spine can cause a rounded posture.
• Osteoporosis and Fractures: Weaker bones can increase the risk of spinal fractures, even after minor trauma.
• Breathing Difficulties: Fusion around the ribs and chest wall can restrict chest expansion and reduce lung capacity.
• Nerve Compression: Advanced spinal changes or fractures can compress nearby nerves or the spinal cord.

Schedule A Spine Evaluation If Ankylosing Spondylitis Pain Persists Despite Treatment!

Persistent pain and stiffness can limit your movement. If your current treatment no longer controls these symptoms, you may have questions about the safety, side effects, dosage, and effectiveness of biologics. However, a specialist evaluation can clarify these concerns and determine which treatment approach suits your condition.

At Total Orthopedics & Sports Medicine, our spine specialists review your symptoms, previous treatments, and overall health before recommending biologic therapy. We also explain the benefits, possible side effects, and dosing schedule based on your treatment needs. With regular monitoring, we can assess your response and adjust treatment to improve daily function. Call 855-321-6784 or visit our New York locations to schedule a spine evaluation.

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