Practice essentials: Addressing the progression of axial spondyloarthritis

By Naveed Saleh, MD, MS | Medically reviewed by David Ozeri, MD, FACP, FACR
Published February 24, 2023

Key Takeaways

  • Long-term suppression of inflammation can mitigate the radiographic progression of axial spondyloarthritis (axSpA).

  • Biologic cytokine inhibitors effectively treat a range of axSpA presentations.

  • Multidisciplinary care is thought to be an optimal approach to the management of patients with axSpA.

Various advances have been made in the understanding and diagnosis of axial spondyloarthritis (axSpA). In some cases, these advances have led to the introduction of new treatments for patients with axSpA.

Ongoing research is helping to shed light on how to use existing and new treatments for this condition, according to the authors of a review published by Rheumatology.[] A better understanding will aid in clinical decision-making for these patients and in the development of treatment recommendations.

Background of axSpA

To treat axSpA, an understanding of the disorder’s trajectory is imperative. This disease often begins when a person is in their 30s, with men at slightly higher risk.

The term axSpA refers to two subpopulations: 1) patients with structural damage to the sacroiliac joint (SIJ) that is evidenced on x-ray (ie, radiographic axSpa or ankylosing spondylitis), or 2) individuals who have not yet advanced to structural damage (ie, non-radiographic axSpA).

Many—but not all—patients with axSpA will progress from the non-radiographic to the radiographic form over time. The inflammation begins at the level of the SIJ and can extend to other parts of the spine, thus causing inflammatory and structural changes.[] The structural changes on x-ray can take years to form, and once they are present, they are irreversible. 

Treatment categories

The long-term suppression of inflammation can attenuate the radiographic progression of axSpA. There are four broad categories for the treatment of axSpA:

  • Exercise and physical therapy

  • NSAIDs, which have been available since the 1950s

  • TNF inhibitors, which were first approved in 2003

  • IL-17 inhibitors, which were first approved in 2016

Following a lull in drug development after the TNF inhibitors, axSpA treatment has expanded with the introduction and approval of two new classes of drugs: IL-17A and JAK inhibitors. There are also several new treatments in phase 3 trials, according to research published by Nature Reviews Rheumatology.[]

Related: Why multidisciplinary teams are crucial in treating nr-AxSpA


Biologic cytokine inhibitors are effective across the gamut of axSpA, with TNF inhibitors used for the treatment of patients with active, moderate-severe axSpA. 

Additionally, the efficacy of IL-17A inhibition is supported by compelling data and points at the central role of the IL-23/IL-17 pathway in spondyloarthritis (SpA) pathogenesis.

The exact mechanism of JAK inhibitors in treating axSpa is not yet known but probably involves the IL-23/IL-17 axis in which several key cytokines function in the JAK-STAT pathway. JAKs are intracellular enzymes that modulate hematopoiesis and immune-cell function.[]

“The JAK/STAT pathway is involved in the signaling of several inflammatory players implicated in the pathogenesis of axSpA,” concluded the author of a review published in Pharmaceuticals.[] “Clinical trials of JAKi [JAK inhibitors] in axSpA have yielded favorable results in key clinical domains of the disease, with an acceptable safety profile."  

"Targeting JAK is thus an attractive and novel therapeutic intervention in this inflammatory rheumatic disease."

Authors, Pharmaceuticals

As of February 2023, upadacitinib is approved to treat radiographic and non-radiographic axSpA.[] Where this agent fits into the treatment strategy of axSpA (eg, first-line, second-line, third-line) remains to be elucidated, per the Pharmaceuticals review.

Prescribing biologics

When prescribing biologic DMARDs (bDMARDs), physicians should consider how likely it is that the patient will respond to the treatment. 

Male sex, HLAB27 positivity, and elevated inflammatory markers are factors not only associated with a poor prognosis but also with higher response rates to TNF inhibitors. 

It is particularly important to treat such patients to prevent erosion and bone formation that are essentially irreversible. 

Other features associated with higher response rates include younger age, shorter disease duration, elevated CRP, and certain inflammatory MRI features. Obesity and smoking, however, are tied to decreased response.

Authors of the review published in Rheumatology further clarified the role of these risk factors.

“These factors are not entirely surprising; the predictors of ‘good response’ essentially reflect a higher likelihood of the patient truly having active inflammatory axSpA, as opposed to other causes of back pain. Therefore, careful clinical assessment and consideration prior to commencing biologics and, again in those who fail to respond to a particular bDMARD, is a crucial part of decision making," the authors wrote.

“Simply applying classification criteria and following treatment guidance using a pre-defined checklist or algorithm approach is not appropriate for clinical practice; the latter requires thoughtful exclusion of other potential causes (such as degenerative disc disease, fibromyalgia) for the patient’s symptoms, which are unlikely to respond to biologics and which require different management strategies,” they added.

Further considerations

There are evidence-based guidelines for the treatment of axSpA, including those from ACR–SAA–SPARTAN and ASAS–EULAR. These guidelines are fairly uniform and offer practical approaches to the management of this disease, according to the Nature Reviews Rheumatology research.

The diagnosis of non-radiographic axSpa is challenging for non-rheumatologists and can complicate the patient’s therapeutic path. The impact of such delays may compromise patient well-being and health.

While multidisciplinary care is not routine for this disease, when administered, it should include input from rheumatologists, radiologists, orthopedists, primary care, physical therapy, and psychiatry. 

What this means for you

For the sake of the patient, non-radiographic axSpa should be identified and treated early. Various factors play into the choice of biologics. This condition is best managed by multidisciplinary teams helmed by rheumatologists. Although guidelines are available for the treatment of this condition, exact approaches are being further explored.

This article is part of Room for Better Rheum Care, where physicians and patients share the latest research, tips, and strategies for raising treatment expectations and delivering improved care in RA, PsA, and nr-AxSpA.

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