Selective inhibition of Janus kinase 1 (JAK1) is safe and effective for treating ankylosing spondylitis (AS) in patients who fail to respond to NSAIDs, according to the results of a new phase II, placebo-controlled trial published in The Lancet.

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Unlike for psoriatic arthritis, inhibition of IL-6 or IL-23 was not effective for treating AS, meaning that current treatment options for patients with AS who do not respond well to NSAIDs are limited to TNF inhibitors and the anti-IL-17A antibody secukinumab. Tofacitinib (a dual JAK1 and JAK3 inhibitor) was effective in a phase II clinical trial, but safety issues are potentially a greater concern when blocking multiple JAKs.

In the current study, 116 patients from seven European countries were randomly allocated 1:1 to receive either 200 mg oral filgotinib (a JAK1 inhibitor) or placebo once daily for 12 weeks. All patients fulfilled the modified New York classification criteria for AS, had previously had an inadequate response to two or more NSAIDs and had radiographically confirmed sacroiliitis and active disease (Bath AS disease activity index (BASDAI) of ≥4 and C-reactive protein concentration of ≥3.0 mg/L).

“The primary endpoint was the change from baseline in the AS disease activity score (ASDAS),” explains corresponding author Désirée van der Heijde. “This was the first time that this endpoint was used as a primary endpoint for a phase II or III trial.” At week 12, the change in ASDAS from baseline was –1.47 (SD 1.04) for those treated with filgotinib and –0.57 (SD 0.82) for those who received placebo (least squares mean difference between groups of –0.85; 95% CI –1.17 to –0.53; P<0.0001). The number of reported adverse events was equal in each group and one patient in each group withdrew owing to an adverse event (pneumonia in the filgotinib group and high creatine kinase in the placebo group).

current treatment options … are limited to TNF inhibitors and the anti-IL-17A antibody secukinumab

“The data show that selective inhibition of JAK1 may be an effective and safe treatment option for patients with active AS who failed treatment with NSAIDs,” says van der Heijde. “Phase III trials should confirm these findings.”