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TORONTO — Currently available drugs to treat patients with axial spondyloarthritis (axSpA) are generally effective for symptom control, and many also for structural protection, but not everyone responds and new agents are being developed to help fill the treatment gap.

That was the message from Akihiro Nakamura, MD, PhD, assistant professor in the Department of Medicine at Queen’s University, Kingston, Ontario, Canada, in his presentation during the Spondyloarthritis Research and Treatment Network (SPARTAN) 2026 Annual Meeting.

Nonsteroidal anti-inflammatory drugs, TNF inhibitors, interleukin (IL)-17 inhibitors, and JAK inhibitors primarily target specific released cytokines (such as TNF and IL-17A/F) or intracellular signaling molecules (JAKs), thereby broadly blocking multiple signaling pathways.

“Despite the overall effectiveness of these treatments, responses among axSpA patients are highly variable,” Nakamura told Medscape Medical News. “In addition, blocking broad signaling pathways may result in unwanted off-target effects and unpleasant side effects”.

Potential Paradigm Shift

Researchers are looking elsewhere to find novel, effective treatments for axSpA.

One approach targets TRBV9 activity. “A potential paradigm shift in axSpA treatment recently emerged following the discovery of expanded autoreactive T cells expressing specific receptors such as TRBV9,” Nakamura said.

One agent in development uses a monoclonal antibody to block the function of T cells expressing specific TRBV chains. A phase 2 randomized trial, conducted primarily in Russia, investigated the efficacy and safety of two doses (5 mg and 7 mg) of the anti-TRBV9 monoclonal antibody (BCD-180) in HLA-B27-positive patients with axSpA. (About 75%-85% of patients with axSpA are positive for the HLA-B27 allele.)

The primary endpoint of the study, which included 260 patients, was the proportion of individuals achieving 40% improvement in the Assessment in Spondyloarthritis International Society (ASAS40) response criteria at week 24.

The study showed response rates were superior in both the 5 mg (40.8%; P = .0417) and 7 mg (51.4%; P = .0012) groups than in the placebo group (24.9%).

The study uncovered significantly superior outcomes for both doses of BCD-180 on a number of secondary endpoints, including a decrease in the proportion of individuals with very high disease activity.

The therapy also had a favorable safety profile. Infusion reactions were the most common adverse events, the vast majority of which were mild-to-moderate in severity.

“This treatment may specifically target harmful autoreactive T cells while sparing nonpathogenic T cells, thereby minimizing off-target effects,” Nakamura said.

The Russian Ministry of Health has approved the drug for axSpA. However, he stressed that efficacy and safety of this treatment needs to be confirmed in more diverse axSpA populations, including those in North America and Europe.

New Cell-Based Treatment Approach

Another promising method to block TRBV9 function is with bispecific T-cell engagers (BiTEs) that recruit cytotoxic killer T cells to block T cells expressing TRBV9.

“Once the BiTE fragments engage CD3-expressing T cells with TRBV9-expressing autoreactive T cells, the CD3-expressing T cells release cytotoxic mediators that kill the TRBV9-expressing autoreactive T cells,” Nakamura explained.

BiTE therapy “represents a potential new cell-based treatment approach” and “a promising future therapeutic approach” for axSpA, he said.

This approach has a number of advantages. For example, it’s possible that BiTE treatment may achieve “profound T-cell depletion,” Nakamura said. “Because BiTE therapy eliminates TRBV9-expressing T cells rather than simply blocking their function, it may more effectively induce deep clinical remission.”

TRBV9-expressing T cells account for only about 4% of total T cells. “So targeting TRBV9 would affect only a small fraction of total T cells, while sparing the majority of nonpathogenic T cells, minimizing off-target effects,” he said.

And as TRBV9-targeting therapies show signs of being highly beneficial for HLA-B27-positive patients, “they may represent a step toward precision medicine,” Nakamura added. “This treatment approach would narrow the target population to HLA-B27-positive patients only.”

He noted that TRBV9-expressing T cells “are thought to expand through interactions with HLA-B27 presented by antigen-presenting cells.”

But he cautioned that TRBV9-expressing T cells likely are likely not the only clonally expanded T-cell population in HLA-B27-positive patients with axSpA. “This treatment approach may not be effective in all HLA-B27-positive patients.”

Nakamura reiterated that more clinical evidence is required to support development of these therapies for axSpA. “The lack of clinical trials specifically targeting TRBV9 suggests that it will likely take years before this approach can be implemented in axSpA,” he said.

Also on the Horizon

Asked what else rheumatologists might expect as possible axSpA treatments, Nakamura noted investigators are looking at a third JAK inhibitor, jaktinib. Research shows this agent exhibits potent activity against JAK2 and tyrosine kinase 2, with lesser effects on JAK3 and minimal effects on JAK1.

One phase 2 study of 107 patients found 75 mg and 100 mg twice daily of jaktinib were superior to placebo in terms of response rates, especially the higher dose, and was effective in improving a variety of indicators of disease activity. For example, ASAS20 response rates were significantly higher in the treatment groups at week 16: 61.1% for 100 mg, 57.1% for 75 mg, and 33.3% for placebo. In addition, the study found the drug to be well-tolerated.

“This is not a completely new target, but it’s a new drug among JAK inhibitors,” Nakamura noted. “Other JAK inhibitors — upadacitinib and tofacitinib — have already been approved in axSpA, but this may be yet another JAK inhibitor to be used for axSpA.”

Again, more data are needed through phase 3 clinical trials, he added.

Looking further down the road, agents with potentially novel targets for axSpA could be developed. Nakamura reported that researchers have discovered new molecules, including B3GNT2, hypoxia-inducible factor, and macrophage migration inhibitory factor, in human samples and preclinical models.

However, he emphasized that “it’s too early to say they’re even in the pipeline right now.”

Nakamura reported receiving speaker fees or honoraria from AbbVie/Abbott and Novartis.