de Vlam, K., Maksymowych, W.P., Gallo, G. et al. (8 more authors) (2024) Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial. Rheumatology and Therapy, 11 (3). pp. 691-707. ISSN 2198-6576
Abstract
Introduction: The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS). Methods: The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers. Results: In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = − 3.9, p < 0.001, adalimumab mean = − 2.6, p < 0.05) compared to placebo (mean = − 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = − 3.7, p < 0.001) versus placebo (mean = − 1.7), improvement with adalimumab did not reach significance (mean = − 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab. Conclusion: This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation. Trial Registration Number: NCT02696785.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024, corrected publication 2024.This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. |
Keywords: | IL-17; Pain; Inflammation; Rheumatic disease; Spondylitis, ankylosing |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Nov 2024 15:35 |
Last Modified: | 05 Dec 2024 13:24 |
Status: | Published |
Publisher: | Springer Nature |
Identification Number: | 10.1007/s40744-024-00660-7 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:219855 |
Commentary/Response Threads
- de Vlam, K., Maksymowych, W.P., Gallo, G., Rahman, P., Mease, P., Krishnan, V., McVeigh, C.J., Lisse, J., Zhu, D., Bolce, R.J. and Conaghan, P.G. Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial. (deposited 20 Nov 2024 15:35) [Currently Displayed]