LONDON — Evidence to support the use of JAK inhibitors in the treatment of axial spondyloarthritis (axSpA) continues to grow based on new reports of positive data from phase 3 studies of filgotinib as well as the investigational agents gecacitinib and ivarmacitinib and a phase 4 study of tofacitinib in early disease.

If the studies’ findings hold up to further scrutiny, three more JAK inhibitors could soon be joining upadacitinib and tofacitinib as approved treatments for axSpA , it was reported during an oral abstract session at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting.

After the presentations, Session Chair Alexandre Sepriano, MD, a rheumatologist at Hospital Egas Moniz and an assistant professor of rheumatology at NOVA University, both in Lisbon, Portugal, told Medscape Medical News: “I think the results are as expected, in that [JAK inhibitors] work.”

Filgotinib — Primary Results of the OLINGUITO trial

Primary results from the OLINGUITO trial reported by Xenofon Baraliakos, MD, PhD, showed that the JAK-1 selective filgotinib significantly improved disease activity relative to placebo within 16 weeks of treatment in patients with active radiographic axSpA (r-axSpA) and in those with nonradiographic axSpA (nr-axSpA).

Improvements occurred as early as week 1 and “were maintained or even increased further up to week 52,” said Baraliakos, EULAR president, head of rheumatology at Rheumazentrum Ruhrgebiet in Herne, Germany, and professor of internal medicine and rheumatology at the Ruhr-Universität Bochum in Bochum, Germany.

The OLINGUITO trial was a pair of ongoing studies in which filgotinib 200 mg once daily was compared against placebo in patients with established axSpA. Study A included 258 patients with r-axSpA, and study B included 237 patients with nr-axSpA. Baraliakos pointed out that recruited participants had a duration of disease of 11-16 years across the study groups, which is “pretty long for this kind of study.” 

Treatment with filgotinib or placebo was blinded for the first 16 weeks, then open label for 1 year, followed by a 1-year dose de-escalation period, and a final open-label extension for a couple more years.

The primary endpoint was the proportion of participants achieving a 40% improvement in Assessment of Spondyloarthritis International Society (ASAS40) response criteria at week 16. This was met by 39.5% of filgotinib- and 20.9% of placebo-treated patients in the r-axSpA study (P = .001) and by 34.5% and 17.8%, respectively, in the nr-axSpA study (P = .003).

Baraliakos also reported that the secondary endpoints were in favor of filgotinib treatment. “The most important one to me is the objective sign of improvement in inflammation,” he said. In both r-axSpA and nr-axSpA, Spondyloarthritis Research Consortium of Canada scores on MRI of the sacroiliac joints were lower with filgotinib than with placebo at 16 weeks, at a respective 1.9 vs 3.8 points for r-axSpA and 2.9 vs 6.2 points for nr-axSpA.

Filgotinib’s safety profile was consistent with its previously reported profile, Baraliakos said. Treatment-emergent adverse events (TEAEs) occurred at similar rates in the filgotinib- and placebo-treated groups in both studies. Only one major adverse cardiovascular event occurred, and that was in the placebo group. There were no instances of venous thromboembolism (VTE), and four recorded instances of malignancy, all in filgotinib-treated patients, none of which were nonmelanoma skin cancer.

Gecacitinib Proves Effective in r-axSpA

Juan Wang, of Renji Hospital in Shanghai, China, and colleagues reported positive data for gecacitinib in people with r-axSpA at the meeting. Gecacitinib, previously known as jaktinib, is a novel pan-JAK inhibitor that was shown in a recent phase 2 study to have significantly greater ASAS20 and ASAS40 response rates than placebo.

The phase 3 study that was presented involved 265 participants with r-axSpA, 133 who were randomly allocated to treatment with gecacitinib 100 mg twice daily and 132 who were given a matching oral placebo. Treatment was double-blind for the first 16 weeks, followed by a 32-week open-label extension phase during which participants already taking gecacitinib could continue it and those on placebo could start taking the drug.

The primary endpoint was ASAS40 at week 16; this was reached by 51.9% of the gecacitinib-treated participants vs 12.9% of those in the placebo group (P < .0001). The treatment effect favoring gecacitinib was apparent at 2 weeks, Wang said.

Among patients who had previously been treated with biologic disease-modifying antirheumatic drugs (DMARDs), the ASAS40 response rate was 58.5% with gecacitinib vs 10.0% with placebo, and for those who had never previously taken a biologic DMARD, the rates were 50.6% vs 15.4%.

In regard to this unique finding, Sepriano said, “[w]e usually see a lower response in patients where they have previously been treated with biological DMARDs, but it seems, that the response was better in this subgroup.”

Secondary endpoints were also improved to a greater extent with gecacitinib than with placebo. For example, ASAS20 at week 16 was reached in a respective 69.2% and 21.2% of participants (P < .0001).

Consistent benefits in disease activity, symptoms, physical function, and quality of life were reported with gecacitinib.

Any TEAE occurred in 87.2% of the gecacitinib group and 78.8% of the placebo group. There was no difference in the number of serious adverse events (3.0% in both groups) or TEAEs leading to treatment discontinuation (2.3% in both groups).

The most common adverse effects of gecacitinib were laboratory abnormalities, but these were manageable and reversible, or improved over time, Wang said.

Treatment of nr-axSpA With Ivarmacitinib

Positive data from a phase 3 trial of the investigational JAK-1 inhibitor ivarmacitinib were also reported at EULAR 2026. Investigators enrolled 304 participants with nr-axSpA who had to have objective signs of inflammation — sacroiliitis on MRI with or without elevated C-reactive protein (CRP). They also had an inadequate response to or were intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).

The study consisted of a 12-week double-blind treatment phase in which participants were randomly allocated to ivarmacitinib 4 mg once daily (n = 151) or to a matching placebo (n = 153), followed by a 12-week extension treatment period where all participants were treated with ivarmacitinib before stopping, and then a 4-week follow-up period.

The primary endpoint of ASAS40 at 12 weeks was reached by 39.7% of participants in the ivarmacitinib group and 24.8% in the placebo group (P = .0057). Again, key secondary endpoints such as ASAS20, among others, favored ivarmacitinib over placebo, with clinical benefits extending into the extension period.

There were no TEAEs of special interest reported, such as VTE. One patient who received ivarmacitinib after placebo died, but the death was not deemed to be treatment related.

Tofacitinib Moves Into the FASTLANE

In the phase 4 FASTLANE study, another group of investigators led by Valeria Rios Rodriguez, MD, of Charité — Universitätsmedizin Berlin in Berlin, Germany, tested the efficacy and safety of giving tofacitinib to patients who met ASAS criteria for axSpA and had objective signs of disease (sacroiliitis on MRI or elevated CRP) but had axial symptoms present for no more than 2 years, with or without radiographic disease. These patients also had an inadequate response to one or more NSAIDs and had not previously taken a biologic or targeted synthetic DMARD.

“Until now, there have been no clinical studies that have prospectively evaluated advanced therapies in this patient population,” Rios Rodriguez said.

A total of 107 participants were randomly allocated to treatment with either tofacitinib 5 mg twice daily or placebo for 16 weeks. Naproxen 500 mg twice daily was also given to all participants.

If disease activity remained high 4 weeks into the study, defined as a Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score of ≥ 4 or < 20% improvement in BASDAI score, participants were switched to open-label tofacitinib with naproxen for the remainder of the study.

The trial’s primary endpoint of inactive disease at week 16, defined as an Axial Spondyloarthritis Disease Activity Score of < 1.3, was met by 26.4% of participants receiving tofacitinib vs 7.4% receiving placebo (P = .006). At 4 weeks, this endpoint was achieved in 13.2% vs 1.9%.

Fewer participants in the tofacitinib group than in the placebo group switched to open-label tofacitinib with naproxen (34.0% vs 57.4%).

“The efficacy of tofacitinib plus naproxen was generally greater than placebo plus naproxen across the efficacy outcomes and imaging,” Rios Rodriguez said. She also noted that the safety of tofacitinib was consistent with previous clinical trials in patients with r-axSpA of longer disease duration.

The OLINGUITO trial was funded by Alfasigma S.p.A., the gecacitinib trial by Suzhou Zelgen Biopharmaceuticals Co. Ltd, the ivarmacitinib trial by Jiangsu Hengrui Pharmaceuticals Co. Ltd., and the FASTLANE trial by Pfizer.

Baraliakos reported having ties with multiple pharmaceutical companies including acting as a speaker, consultant, and investigator for Alfasigma S.p.A. Rios Rodriquez declared having ties with Pfizer, AbbVie, Eli Lily and Company, Johnson & Johnson, Novartis, Takeda, and UCB. Wang and Sepriano reported having no relevant financial relationships.

Sara Freeman, MSc, is a freelance medical journalist based in London, England. She has been reporting for specialist healthcare news organizations for more than 20 years.