Axial Spondyloarthritis: Treatment Update | MedPage Today

For patients with axial spondyloarthritis (axSpA) who do not benefit from or cannot take nonsteroidal anti-inflammatory drugs (NSAIDs), new treatment options include agents in multiple drug classes.

Spondyloarthritis (SpA) has two manifestations: axSpA, which predominantly affects the spine and sacroiliac joints, and peripheral SpA, which affects the peripheral joints. Axial spondyloarthritis can be either radiographic axSpA (synonymous with ankylosing spondylitis) or non-radiographic axSpA.

Patients with radiographic axSpA and non-radiographic axSpA often are similar in clinical presentation, burden of disease, treatment received, and response. Treatment is geared to reducing pain and stiffness and reducing disease progression to prevent deformity and maintain function.

“The optimal management of patients with axSpA requires a combination of non-pharmacological and pharmacological treatment modalities,” according to recommendations published by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism (ASAS-EULAR) in 2022. Lifestyle modifications, physical activity, and patient education are essential components, the recommendations noted.

Treatment Options

The first-choice pharmacological treatment for axSpA are NSAIDs, and dosing may be higher than usual. Sulfasalazine may be used when peripheral joints are affected in addition to axial joints if NSAIDs are insufficient, the ASAS-EULAR guidelines suggested.

Not all patients respond, though, and some cannot take NSAIDs. Other treatments include tumor necrosis factor (TNF) inhibitors, monoclonal antibodies targeting interleukin (IL)-17, and Janus kinase (JAK) inhibitors.

In September, the IL-17 agent bimekizumab (Bimzelx) — which targets IL-17A and IL-17F — was approved by the FDA for active non-radiographic axSpA with objective signs of inflammation and ankylosing spondylitis. It was approved for axSpA in Europe in 2023.

This approval was welcome in the rheumatology community because there are few options to treat both forms of axSpA, noted Atul Deodhar, MD, of Oregon Health and Science University in Portland.

“The treatment options for axSpA have been limited to NSAIDs, TNF inhibitors, IL-17A inhibitors, and JAK inhibitors,” Deodhar told MedPage Today. “We now have a new modality of treatment, bimekizumab, that blocks two cytokines: IL-17A and IL-17F.”

“The BE-MOBILE 1 and BE-MOBILE 2 studies showed that inhibiting IL-17A and IL-17F is effective in the entire spectrum of axSpA, both non-radiographic and radiographic forms,” he pointed out.

“There’s a hint that bimekizumab may be equally effective in biologic-naive and TNF inhibitor inadequate-responder patients with axSpA,” Deodhar added. “Whether blocking IL-17A and IL-17F is more effective than blocking IL-17A alone is unclear. Only head-to-head studies will tell us that.”

In the parallel phase III BE-MOBILE trials, 45% and 48% of those treated with bimekizumab had at least 40% improvement in the primary endpoint of ASAS ratings at week 16, compared with 21% and 23% of patients who received placebo (both P

After 1 year of continuous treatment with bimekizumab, more than 60% of patients in BE-MOBILE 1 and BE-MOBILE 2 were classified as responders. Participants initially randomized to placebo but switched to bimekizumab after week 16 achieved similar responses by week 52.

Treatment Comparisons

The choice between TNF and IL-17 inhibitors to treat axSpA has been mainly guided by the presence of extra-articular manifestations, noted Eric Toussirot, MD, of Centre d’Investigation Clinique in Besançon, France, in a review article.

“JAK inhibitors were more recently introduced for the treatment of radiographic axSpA, but their use is restricted to specific patients with a safe cardiovascular profile,” he wrote.

TNF inhibitors include adalimumab (Humira), infliximab (Remicade), etanercept (Enbrel), certolizumab pegol (Cimzia), and golimumab (Simponi). Besides bimekizumab, IL-17 inhibitors are secukinumab (Cosentyx) and ixekizumab (Taltz).

JAK inhibitors include tofacitinib (Xeljanz) and upadacitinib (Rinvoq). The FDA requires a boxed warning about the risks of serious cardiovascular events, cancer, blood clots, and death for these drugs, based on safety data from a tofacitinib clinical trial.

The three drug classes were compared in a 2024 retrospective analysis of real-world axSpA patients started on one of the treatment types between 2015 and 2023. Bimekizumab was not included due to its recent approval.

The study found significantly higher rates of discontinuation for JAK inhibitors compared with TNF inhibitors (HR 1.91) or IL-17 inhibitors (HR 1.43), possibly related to more frequent use of TNF inhibitors as first-line therapy, or to more severe or refractory disease in those treated with JAK or IL-17 inhibitors. The most common period of treatment discontinuation was during the first 12 months after treatment initiation, due to a lack of effectiveness.

A recent systematic review and network meta-analysis evaluated randomized controlled trial data for bimekizumab and relevant biologic or targeted synthetic disease-modifying anti-rheumatic drugs. Among predominantly naive non-radiographic axSpA patients, bimekizumab had higher response rates than the IL-17 inhibitor secukinumab and similar response rates as most other drugs, including TNF inhibitors, the IL-17 inhibitor ixekizumab, and the JAK inhibitor upadacitinib. Bimekizumab had a safety profile comparable to other agents.