What to Know: Biologics for Non-Radiographic Axial Spondyloarthritis

Getting Started

Non-radiographic axial spondyloarthritis (nr-axSpA) is a type of inflammatory arthritis that occurs in the spine. Nr-axSpA causes inflammation that leads to stiffness, swelling, and pain.

Nr-axSpA is treatable, and treatment is focused on helping a person to feel better and slow down the disease's progress. Treatment options might include nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and biologic drug therapies.

Biologic drug therapies are the newest option for treating nr-axSpA. They can help provide symptom relief, prevent joint damage, and improve the quality of life for people who have nr-axSpA.

Keep reading to learn about how biologics might benefit you, how they work, and how to get started.

Non-Radiographic Axial Spondyloarthrtis (nr-axSpA) Treatment Types

Verywell / Zoe Hansen

What Is Nr-axSpA?

Nr-axSpA is part of a group of inflammatory diseases that fall under an umbrella category of diseases called spondyloarthritis. Nr-axSpA is in a specific category called axial spondyloarthritis (axSpA).

AxSpA also includes ankylosing spondylitis (AS), another type of spondyloarthritis that causes the small bones of the spine (vertebrae) to fuse. AS usually includes evidence of sacroiliitis (inflammation of the sacroiliac joint, the connection of your spine and pelvis) on X-ray, while nr-axSpA does not. It's not clear if these conditions are overlapping or distinct entities.

What makes nr-axSpA different from other types of inflammatory arthritis or spinal arthritis is that while it causes symptoms of spinal arthritis, X-rays don’t always show definite damage to parts of the spine or other affected joints. This does not mean inflammation isn't occurring.

For most people, nr-axSpA disease onset is usually in early adulthood, with an average age of onset of 28 years of age. In the United States, nr-axSpA affects around 0.9% to 1.4% of the population.

People with nr-axSpA experience significant inflammatory back pain, severe and prolonged joint stiffness and swelling, buttocks pain, heel pain, and chronic fatigue. The condition also causes inflammation of the joints that connect to the pelvis and spine—the sacroiliac joints.

Nr-axSpA does not cause radiological (X-ray) evidence of damage or ongoing inflammation of the pelvis or spine.

The condition requires early diagnosis and treatment. But for many people with the condition, it can take years to get a diagnosis. Both types of axial spondyloarthritis (nr-axSpA and AS) are difficult to diagnose, with nr-axSpA causing a longer delay toward diagnosis.

Research presented in 2018 showed it takes an average of seven years for doctors to pinpoint a cause of ongoing inflammation. Oftentimes, this doesn’t happen until there is radiological damage to the joints of people with axSpA.

Over time, some people with nr-axSpA will go on to develop AS. Damage from AS is irreversible and detectable by X-ray. A 2016 study reported in the journal Arthritis Research & Therapy found that approximately 10% of people with nr-axSpA went on to develop AS within two years and up to 60% developed AS in 10 years.

Biologics for Treating Nr-axSpA

Treatment for nr-axSpA starts with managing pain and reducing inflammation. For many people, NSAIDs and physical therapy are generally effective.

Conventional disease-modifying anti-rheumatic drugs (DMARDs) are usually not prescribed for spinal diseases. The use of conventional DMARDs, like methotrexate and sulfasalazine, is considered only when joints other than the back, spine, and pelvis are affected, such as the peripheral joints of the arms and legs (i.e., knees or elbows, wrists or ankles).

Corticosteroids are given to fight inflammation that affects other joints. But injections are usually not given into the spine and oral corticosteroids are not prescribed to treat inflammation that is limited to the back, spine, and pelvis.

Tumor necrosis factor (TNF) inhibitors and interleukin 17 (IL-17) inhibitors are an alternative to conventional DMARDs for treating nr-axSpA. TNF inhibitors are a first-line biologic DMARD for nr-axSpA, while IL-17 inhibitors are second-line biologic treatments and given to people who have had inadequate responses to anti-TNF therapy.

TNF Inhibitors

When initial treatments for nr-axSpA don’t work, the American College of Rheumatology (ACR) recommends adding TNF inhibitors—biologics that target molecules responsible for inflammation.

Cimzia (certolizumab pegol) is the only TNF inhibitor approved in the United States by the Food and Drug Administration (FDA) for managing nr-axSpA. Other TNF inhibitors are also used for treatment, but off-label (without specific approval for the condition).

Research on Cimzia shows that this TNF inhibitor can rapidly reduce symptoms of axSpA conditions safely and effectively. Cimzia research has found similar improvements for people with both nr-axSpA and AS.

Interleukin 17 (IL-17) Inhibitors

In June 2020, the FDA approved two additional biologic medications—Taltz (ixekizumab) and Cosentyx (secukinumab)—to treat active nr-axSpA. Both Taltz and Cosentyx are interleukin 17 (IL-17) inhibitors—this means they inhibit IL proinflammatory molecules found in the blood serum of people with nr-axSpA.

In clinical trials, Taltz was found to be safe and effective for reducing symptoms and inflammation of nr-axSpA. Here, researchers determined that Taltz provided symptom relief for people experiencing debilitating back pain and fatigue from nr-axSpA.

By week 16, up to 40% of the study participants showed improvement, and 31% had continued improvement at week 52.

The safety and efficacy of Cosentyx were confirmed in a 2019 study reported in the Annals of Rheumatic Diseases. Here, the study participants who used Cosentyx experienced an up to 40% improvement by week 16, and many of those improvements continued by week 52.

At week 16, 41.5% of the study participants in the treatment group indicated improvement of symptoms. At week 52, 35.4% of the study participants were still reporting improvement.

Off-Label Biologic Treatments for Nr-axSpA

Other biologic drug therapies have been used to treat nr-axSpA. These have been prescribed off-label, which means they are being prescribed in a manner that is not specified in the FDA’s labeling.

One study, reported in 2020 in the journal Rheumatology and Therapy, of 495 nr-axSpA patients found that more than half (59.6%) were being treated with a biologic. Among those, 48.1% were receiving a biologic without a conventional DMARD and 11.5% were receiving a biologic with a conventional DMARD.

Of the 295 study participants treating with a biologic, 77.8% were receiving their first biologic, 13.8% their second, and 8.3% had tried three or more biologics.

Biologics used by the study participants include the three that have been FDA approved for treating nr-axSpA (Cimzia, Taltz, and Cosentyx), plus adalimumab, etanercept, infliximab, and golimumab. Up to 60% of the study participants were receiving a biologic drug before the FDA approval of any biologic for treating nr-axSpA.

What to Expect

Biologic drug therapies are given either by injection or IV infusion (intravenously using a needle in the arm). You can give yourself a biologic injection in the comfort and privacy of your home. Biologic drug infusions are done at your doctor’s office, an infusion center, or a hospital.

Cimzia, Taltz, and Cosentyx are given by injection. Some biologic drugs used off-label for nr-axSpA are given by infusion.


Biologic drug injections come either as prefilled syringes or as pen-type injectors. These are usually subcutaneous injections, where you use a short needle to inject a drug into the tissue layer between the skin and the muscle. Subcutaneous injections are given in an area of skin that can be pinched—e.g., your thigh or abdomen.

Biologic injections are usually stored in the refrigerator and taken out to gradually warm to room temperature before the injection. Each biologic comes with preparation and dosing instructions.

The dosage for a biologic injection will depend on the drug prescribed. Some are given once or twice weekly, some every other week, and others are once a month. Your doctor can answer questions you have about different doses for different biologic treatments.

Your doctor’s office can answer any questions you have about a specific biologic for treating nr-axSpA. They can walk you through the steps for injecting yourself. The instructions will also be included in the medicine's labeling.


A biologic infusion is given through an IV drip into a vein. An infusion session can take two or more hours. Most people have infusion treatments done every few weeks. These appointments take place in a medical setting.

Pre-medications are given to prevent any drug infusion reactions or side effects prior to the infusion. When it is time for your infusion, the technician will place an IV into a vein. Once the IV is placed, the infusion will be started, and the medicine will move through the tube into your vein.

After the first infusion, you will be monitored for at least an hour for any signs of a drug allergic reaction. Signs of an allergic reaction include skin rash, itching, swelling, shortness of breath, or wheezing. You will be given information about side effects to watch out for and a number to call after leaving the clinic.

The effects of a biologic drug will become evident weeks after your first infusion treatment. You should start to see the full effects of the biologic after you have a few infusions. That improvement can last for many months.

Risks and Side Effects

Biologics are believed to cause fewer side effects than traditional DMARDs. This is because they target only one part of the inflammatory process rather than targeting the whole immune system. However, side effects caused by biologic drug therapies can sometimes be very serious.

You may be at greater risk of infections when using a biologic. This includes common infections, such as upper respiratory infections and pneumonia, and less common infections, like tuberculosis and fungal infections.

Research suggests that the risk of infection with TNF inhibitor biologics is greatest during the first six months after starting treatment.

You should report any signs of an infection to your doctor. Signs of infection might include fever, chills and sweats, sore throat, shortness of breath, stiff neck, nasal congestion, and pain and/or burning with urination.


If you end up with an infection while on a biologic, your doctor will likely recommend that you stop taking the drug until the infection is cleared.

Some people on biologic drug therapy might experience an allergic reaction or even anaphylactic shock, a severe, potentially life-threatening allergic reaction. Research finds that allergic reactions and anaphylactic shock are more common with TNF inhibitors. Of these reactions, 86.4% were considered non-serious, 13.2% were serious, and 0.38% were fatal.

An allergic reaction to a biologic can cause rash and itchiness at the injection or infusion site. Some people might experience a full-body rash.

A severe reaction might cause swelling of the lips or throat and lead to breathing troubles. Reach out to your doctor if you think you are experiencing an allergic reaction to your biologic drug treatment.

Other side effects that biologics can cause include:

  • Fatigue
  • Weakness
  • Digestive symptoms, including diarrhea, constipation, nausea, or vomiting
  • Coughing
  • Vision problems
  • Numbness or tingling
  • Swelling of the hands or ankles
  • Headache

Your doctor can’t predict what side effects your biologic treatment might cause you. You should report to your doctor side effects for new treatments or new side effects that occur after you have been treating for some time.

Questions About Side Effects

While some side effects of biologics might seem scary or concerning, your doctor has reviewed the benefits and risks associated with biologic treatment for nr-axSpA, and they have determined that the drug’s benefits outweigh the risks.

Any questions and concerns about side effects should be directed to your doctor. Don’t stop any medicine without first talking to your doctor because discontinuing treatment abruptly can lead to unpleasant side effects or worsening of disease symptoms.

Getting Started

A biologic drug is likely to be a first-line treatment for axial spondyloarthritis, including nr-axSpA. Your doctor will discuss how biologic drug therapy can help you to manage nr-axSpA.

Before picking a biologic drug therapy to manage your symptoms, your doctor will want to determine if you are a candidate for a particular biologic. They will do this by making a full assessment of your health, which includes your medical history, a physical exam, blood work, imaging, and additional testing.

Your doctor also needs to know all the other medications you take, including vitamins and supplements. Some medicines and supplements shouldn’t be taken with biologics because taking them together could lead to a drug interaction. A drug interaction changes the way a drug works or it can increase the risk and severity of side effects.

Anyone who is sick should hold off on starting a biologic. This is because biologic treatment suppresses your immune system, which could increase your infection risk.

You will be screened for certain infections, including tuberculosis, before starting a new biologic. Your doctor may also suggest you get all necessary vaccines before starting a biologic drug.

You should also talk to your doctor about your risk for certain types of cancer. Some biologic drugs have been linked to skin cancers and lymphoma. This increased risk doesn’t mean you should avoid biologic drug therapy for nr-axSpA. Rather, it means your doctor will monitor your cancer risk while you are treating with a biologic.


Biologic medications for non-radiographic axial spondyloarthritis aim to reduce inflammation by targeting specific aspects of the inflammatory process. Cimzia, Taltz, and Cosentyx have been approved to treat the condition. They are given by injection. Side effects include an increased risk of infection and possible allergic reactions.

Frequently Asked Questions

Can I afford biologics to treat nr-axSpA?

Biologics can cost anywhere from $10,000 to $30,000 a year. Your healthcare insurance will sometimes cover most of the cost, but you might still have significant out-of-pocket costs.

Fortunately, many drug manufacturers offer patient assistance programs that can reduce cost and improve access to therapies needed to treat your nr-axSpA. Your doctor's office might be able to offer additional information about help with drug costs.

For example, they may have information about a clinical drug trial where the medication would be available at no cost to you. Or they might have information about patient assistance programs for people without insurance or for people who have insurance that doesn't cover expensive therapies.

How long before I feel better?

Nr-axSpA symptom improvement takes time. It could take three or more months before you start to experience less inflammation and pain from nr-axSpA.

If you have been treating with a biologic for at least three months and see little or no improvement, reach out to your doctor. You may need a different dosage, an additional treatment, or a different biologic to better manage nr-axSpA.

How is nr-axSpA diagnosed?

Your doctor will want to know what symptoms you are experiencing and will order blood work. They will also rely on magnetic resonance imaging (MRI) to confirm a diagnosis of nr-axSpA. MRIs can detect inflammation of the sacroiliac joints of the pelvis before there are bone changes on X-rays.

If the MRI and blood work are inconclusive, a diagnosis of nr-axSpA can be made and treatments can be prescribed based on your symptoms and other disease characteristics if those meet the criteria of the Assessment of Spondyloarthritis International Society for nr-axSpA.

A Word From Verywell

You might have to try different biologic drugs before finding one that best works to manage your symptoms and reduce inflammation in your back, spine, and pelvis. It is also important that you keep all follow-up medical appointments so your doctor can assess you to make sure a biologic is still working.

When you see your doctor, you should let them know about side effects that you find bothersome or difficult to handle and whether you feel your treatment plan is helping you to feel better and improving your quality of life.

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By Lana Barhum
Lana Barhum has been a freelance medical writer since 2009. She shares advice on living well with chronic disease.