Brief Paper
Symptomatic and structural benefit of cathepsin K inhibition by MIV-711 in a subgroup with unilateral pain: post-hoc analysis of a randomised phase 2a clinical trial
A.R. Bihlet1, I. Byrjalsen2, J.R. Andersen3, F. Öberg4, C. Herder5, M.A. Bowes6, P.G. Conaghan7
- NBCD A/S, Herlev, Denmark. abi@nbcd.com
- NBCD A/S, Herlev, Denmark.
- NBCD A/S, Herlev, Denmark.
- Medivir AB, Huddinge, Sweden.
- Medivir AB, Huddinge, Sweden.
- iMorphics, Manchester, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds, UK.
CER15118
2022 Vol.40, N°5
PI 1034, PF 1037
Brief Paper
PMID: 35238765 [PubMed]
Received: 30/08/2021
Accepted : 23/11/2021
In Press: 25/02/2022
Published: 13/05/2022
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.
