Background: Vunakizumab is a recombinant humanized IgG1/κ monoclonal antibody targeting IL-17A [1]. In a randomized phase 2/3 trial, vunakizumab was well tolerated and significantly improved signs and symptoms of ankylosing spondylitis in patients with active disease [2].

Objectives: We reported here the effect of vunakizumab treatment over 32 weeks on patient-reported outcomes.

Methods: In this randomized, double-blind, adaptive, seamless, phase 2/3 trial (NCT04840485), patients with active ankylosing spondylitis were randomized to receive vunakizumab 120 mg, 240 mg, or placebo (2:2:1) in the phase 2 part and to receive vunakizumab 120 mg or placebo (2:1) in the phase 3 part at baseline and weeks 2, 4, 8 and 12. After primary efficacy assessment at week 16 (core period), patients who were originally assigned to placebo were reassigned to receive vunakizumab (1:1 to 120 mg or 240 mg in the phase 2 part; 120 mg in the phase 3 part) every four weeks through week 32 (extension period). Patients in the vunakizumab groups continued the therapy every four weeks through week 32. Patient-reported outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form 36 (SF-36) physical component summary (PCS) score and mental component summary (MCS) score, Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, total back pain; nocturnal back pain, and patient’s global assessment of disease activity. The differences between vunakizumab 120 mg and placebo treatment in patient-reported outcomes (except for SF-36) at week 16 were analyzed using mixed-effects model repeated measures (MMRM), with treatment groups, visit, weight, and anti-TNF status as factors, and respective baseline score as covariates. Changes in SF-36 from baseline at week 16 were analyzed based on analysis of the covariance model. The results at week 32 were analyzed using descriptive statistics.

Results: Overall, 294 patients were allocated to vunakizumab 120 mg and 146 were to placebo. At week 16, patients treated with vunakizumab 120 mg showed significant improvement from baseline in BASDAI (-2.69 [1.67] vs. -1.74 [1.62], p<0.0001), BASFI (-1.72 [1.85] vs. -0.97 [1.76], p<0.0001), SF-36 PCS score (6.39 [6.58] vs. 3.64 [5.80], p=0.0002), SF-36 MCS score (3.69 [9.17] vs. 1.84 [8.54], p=0.0443), ASQoL (-3.47 [3.87] vs.-2.16 [3.69], p<0.0001), total back pain (-2.89 [2.11] vs. -1.83 [2.06], p<0.0001), nocturnal back pain (-3.06 [2.20] vs. -1.76 [2.20], p<0.0001), and patient’s global assessment of disease activity (-2.91 [2.02] vs. -1.66 [2.18], p<0.0001) when compared with patients treated with placebo. All improvements were sustained through week 32 (Figure 1).

Conclusion: Treatment with vunakizumab provides significant and sustained improvements in patient-reported disease activity, functional impairment, health-related quality of life, and pain in patients with active ankylosing spondylitis.

REFERENCES: [1] Keam SJ. Drugs 2024; 84:1481-1485.

[2] Huang F, et al. Annals of the Rheumatic Diseases 2024;83:904-905.

Figure 1.

Least squares (LS) mean change from baseline through week 32 in the BASDAI (A), BASFI (B), SF-36 PCS score (C) and MCS score (D), ASQoL (E), total back pain (F); nocturnal back pain (G), and PGADA (H). BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; SF-36, Short Form 36; PCS, physical component summary; MCS, mental component summary; ASQoL, Ankylosing Spondylitis Quality of Life; PGADA, patient’s global assessment of disease activity.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.