Xeligekimab (an interleukin-17A antagonist) has shown promising efficacy in the relief of stiffness in patients with active radiographic axial spondyloarthritis (r-axSpA) based on its phase III trial(NCT05881785). Nevertheless, the detailed response signature of stiffness after the treatment such as the duration and severity of stiffness, response charateristics stratified by severity of stiffness at baseline were not fully delineated. This post hoc analysis aimed to assess the detailed remission signatures of xeligekimab on stiffness in patients with active r-axSpA.

This post-hoc analysis utilized data from a multicenter, randomized, double-blind, placebo-controlled phase III trial (NCT05881785) in which r-axSpA patients were randomized to receive xeligekimab 100 mg, 200 mg, or placebo. Patients with active r-axSpA who presented stiffness (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores >0 for questions [Q] 5 and Q6) were collected. Key efficacy endpoints included the changes from baseline in the mean of BASDAI Q5 plus Q6 (BASDAI Q5 & Q6), Q5, and Q6 at weeks 2, 4, 8, 12, and 16, as well as the proportions of patients whose mean of BASDAI Q5 & Q6 dropped to 0 (complete response) and decreased by 50% from baseline at week 16. Efficacy analyses were further stratified based on the mean of baseline BASDAI Q5 & Q6.

A total of 461 patients were included in this analysis (xeligekimab 100 mg: n = 152; xeligekimab 200 mg: n = 154; placebo: n = 155). Mean BASDAI Q5 & Q6 at baseline was 5.46. Both xeligekimab doses were superior to the placebo in improving stiffness at week 2, with significantly greater mean percentage changes in BASDAI Q5 & Q6 in the 100 mg (-20.6%) and 200 mg (-19.1%) groups versus the placebo group (-9.7%) (both p <0.05) (Table 1). This improvement was sustained throughout the 16-week period with mean changes of -45.9% (xeligekimab 100 mg) and -50.1% (xeligekimab 200 mg) versus -25.1% for placebo at week 16 (both p <0.05, Table 1). This therapeutic effect was consistent irrespective of the severity of stiffness (baseline BASDAI Q5 & Q6 ≤5.46 or >5.46) (Table 1). The severity of stiffness (BASDAI Q5) showed increasing improvement with both xeligekimab doses from week 2 to week 16, resulting in 50.5% and 45.4% decreases from baseline at week 16 in patients treated with xeligekimab 200 mg and 100 mg, respectively (Figure 1A). Duration of stiffness was also significantly shortened with mean reductions in BASDAI-Q6 achieving -2.7 for xeligekimab 200 mg and -2.4 for xeligekimab 100 mg versus -1.4 for placebo at week 16 (both p <0.05, Figure 1B). Both xeligekimab doses demonstrated superiority over placebo in the proportion of patients achieving complete remission of stiffness at week 16 (100 mg: 8.6%, 200 mg: 8.4% vs. placebo: 0.6%, p <0.05). Similarly, a markedly higher proportion of patients in the xeligekimab groups achieved a 50% decrease in BASDAI Q5 & Q6 at week 16 (100 mg: 52.0%, 200 mg: 55.8% vs. placebo: 29.7%, p <0.05).

Xeligekimab significantly improved not only the severity of stiffness but also the duration of stiffness in r-axSpA patients regardless the severity of stiffness at baseline. A higher proportion of patients achieved complete remmision in stiffness after treatment at week 16.