New JAK inhibitors in the axSpA treatment landscape Save

JAK inhibitors are now firmly established within the axial spondyloarthritis (axSpA) treatment landscape, with several agents already approved for both radiographic and non-radiographic disease. At EULAR 2026, two large phase 3 studies highlight that the JAK story in axSpA is still evolving rapidly, with different selectivity profiles and expanding global development programs continuing to push the field forward.

The studies evaluated ivarmacitinib, a selective JAK1 inhibitor, in non-radiographic axSpA (nr-axSpA), and gecacitinib, a novel pan-JAK inhibitor, in radiographic axSpA (r-axSpA/ankylosing spondylitis). Together, they provide further evidence that oral targeted therapies are becoming increasingly sophisticated across the full axSpA spectrum.

Ivarmacitinib in Non-Radiographic axSpA (OP0237)

The phase 3 ivarmacitinib trial enrolled 304 patients with active nr-axSpA and objective evidence of inflammation by MRI and/or elevated CRP despite inadequate response or intolerance to NSAIDs.

At 12 weeks, the primary endpoint was met, with ASAS40 responses significantly higher with ivarmacitinib compared with placebo (39.7% vs 24.8%). Improvements were also seen across multiple secondary endpoints, including ASDAS-CRP, BASDAI, ASAS20, BASFI and quality-of-life measures.

Importantly, responses appeared to persist. By week 24, after placebo patients crossed over to active treatment, ASAS40 responses exceeded 56% in both groups. While efficacy itself is not unexpected for JAK inhibition in axSpA anymore, the study is notable for several reasons. First, it adds another positive phase 3 dataset specifically in nr-axSpA, a population where treatment access and therapeutic options still vary internationally. Second, it reinforces the idea that selective JAK1 inhibition may provide meaningful efficacy in axial inflammation while potentially avoiding broader JAK pathway inhibition.

Safety findings were reassuring overall. Serious adverse events were rare, infection rates were similar between groups, and notably no cases of major adverse cardiovascular events, venous thromboembolism, tuberculosis, or malignancy were reported during the study period.

Gecacitinib in Radiographic axSpA (OP0240)

The second major abstract focused on gecacitinib, also known as Jaktinib, a novel pan-JAK inhibitor evaluated in active radiographic axSpA. This placebo-controlled phase 3 study randomized 265 patients, including both biologic-naïve and biologic-experienced populations. At week 16, ASAS40 responses reached 51.9% with gecacitinib versus only 12.9% with placebo. ASAS20 responses were similarly impressive at 69.2% versus 21.2%.

Importantly, the benefits extended beyond symptomatic improvement alone. Significant improvements were observed across measures of physical function, spinal mobility, quality of life and MRI inflammation scores in both the spine and sacroiliac joints, a demonstration of objective suppression of inflammatory activity.

Subgroup analyses suggested efficacy in both biologic-naïve and biologic-experienced patients, raising the possibility that gecacitinib may ultimately have utility across different lines of therapy. As with ivarmacitinib, safety over the placebo-controlled period appeared broadly acceptable, with no unexpected safety concerns emerging during the first 16 weeks.

What do these studies add to our understanding of treatment in axSpA?

Perhaps the most interesting aspect of these studies is not simply that they were positive, but that they reflect how diversified the JAK field in axSpA is becoming. We are now seeing selective JAK1 inhibitors, broader pan-JAK inhibitors, and agents with differing pharmacologic profiles all entering late phases of clinical trials and development. The broader impacts on efficacy, safety, extra-musculoskeletal manifestations, or long-term structural outcomes remain an important unanswered question.

The studies also underscore the increasingly global nature of rheumatology drug development. Both trials were large multicentre Chinese phase 3 programs, highlighting the growing influence of Asian clinical research networks and pharmaceutical development pipelines within rheumatology.

Of course, long-term safety remains central to any discussion around JAK inhibition, especially regarding cardiovascular events, malignancy, and thrombosis. While neither study identified major safety signals in the short term, placebo-controlled studies of 12-16 weeks cannot fully address these longer-term risks.

JAK inhibition has firmly found its home in the treatment of axSpA. The next phase of the field will likely focus on differentiation between selectivity profiles, safety strategies, patient subgroups, and their positioning relative to the more established biologic therapies.

Dr Mrinalini Dey