Bihlet, AR, Byrjalsen, I, Andersen, JR et al. (4 more authors) (2022) Symptomatic and structural benefit of cathepsin K inhibition by MIV-711 in a subgroup with unilateral pain: post-hoc analysis of a randomized phase 2a clinical trial. Clinical and Experimental Rheumatology, 40 (5). pp. 1034-1037. ISSN 0392-856X
Abstract
OBJECTIVES:
Osteoarthritis (OA) development programmes face challenges due to discordance between structural changes and symptoms. A novel cathepsin-K inhibitor, MIV-711, recently reported structural benefits, but did not demonstrate a significant difference from placebo in symptoms. Previous work suggests that pain from non-target joints may confound OA pain outcomes. We therefore conducted an exploratory analysis in participants with predominantly unilateral knee pain from the MIV-711-201 trial. METHOSD: Participants scoring below median contralateral knee NRS pain at baseline from the MIV-711-201 phase 2a clinical trial (n=119) were analysed by treatment group for differences in change from baseline in WOMAC pain, quantitative magnetic resonance imaging bone area and cartilage thickness with a repeated-measures mixed model adjusting for relevant co-variates.
RESULTS:
In the subgroup with unilateral knee pain, treatment with MIV-711 100 mg led to greater reduction in WOMAC pain compared to placebo (-5.0, 95% CI: -8.69 to -1.3, p=0.008), while 200 mg did not (-2.5, 95% CI: -6.5 to 1.6, p=0.23). MIV-711 treatment was associated with a reduced change in bone area compared to placebo (200 mg; -19.6 mm2 , 95% CI: -36.2 to -3.0, p=0.02, and 100 mg; -12.5 mm2 , 95% CI: -27.8 to 2.8, p=0.11,). No observed differences between treatment groups in cartilage thickness were found in this subgroup.
CONCLUSIONS:
In a subgroup with predominantly unilateral knee pain, significant reduction in OA pain by MIV-711 100 mg treatment was found, with concurrent beneficial structural effects, highlighting the importance of appropriate pain inclusion criteria in OA trials.
Metadata
Item Type: | Article |
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Authors/Creators: |
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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: | 16 Mar 2022 14:46 |
Last Modified: | 27 Mar 2023 15:08 |
Published Version: | https://www.clinexprheumatol.org/abstract.asp?a=17... |
Status: | Published |
Publisher: | Pacini Editore SpA |
Identification Number: | 10.55563/clinexprheumatol/1kvgte |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:184743 |