Tambiah, JRS, Kennedy, S, Swearingen, CJ et al. (4 more authors) (2021) Individual Participant Symptom Responses to Intra-articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial. Rheumatology and Therapy, 8. pp. 973-985. ISSN 2198-6584
Abstract
Introduction
Established thresholds for patient-reported outcomes (PROs) provide clinically relevant responder data from trials. Lorecivivint (LOR) is an intra-articular (IA) therapy in development for knee osteoarthritis (OA). A post hoc analysis from a phase 2b trial (NCT03122860) determined proportions of LOR responders.
Methods
A 24-week, randomized trial of 0.07 mg LOR demonstrated PRO improvements compared with PBO in moderate-to-severe knee OA participants. Participants treated with LOR and PBO achieving 30%/50%/70% improvements at weeks 12 and 24 in Pain Numeric Rating Scale (NRS), WOMAC Pain/Function subscales, Patient Global Assessment (PtGA), and OMERACT-OARSI responder criteria were determined. Odds ratios (ORs) and 95% confidence intervals [CIs] were compared with PBO.
Results
There were 115 and 116 participants in the LOR and PBO groups, respectively. For Pain NRS, LOR increased ORs of achieving 30% [week 12, OR = 2.47 (1.45, 4.19), P < 0.001; week 24, OR = 2.37 (1.40, 4.02), P < 0.01] and 50% [week 24, OR = 1.89 (1.11, 3.23), P < 0.05] improvements over baseline. For WOMAC Pain, LOR increased ORs of achieving 30% [week 24, OR = 1.79 (1.06, 3.01), P < 0.05] and 50% [week 12, OR = 1.79 (1.06, 3.03), P < 0.05; week 24, OR = 1.73 (1.02, 2.93), P < 0.05] improvements. For WOMAC Function, LOR increased ORs of achieving 30% [week 12, OR = 1.85 (1.10, 3.12), P < 0.05; week 24, OR = 1.93 (1.14, 3.26), P < 0.05] improvements. For PtGA, LOR increased ORs of achieving 50% [week 12, OR = 2.28 (1.25, 4.16), P < 0.01] improvements. LOR produced numerical increases at the 70% threshold. LOR increased ORs of achieving OMERACT-OARSI responses [week 12, OR = 2.21 (1.29, 3.78); P < 0.01; week 24, OR = 2.57 (1.49, 4.43), P < 0.001] and strict responses [week 12, OR = 2.13 (1.26, 3.61), P < 0.01; week 24, OR = 2.05 (1.21, 3.47), P < 0.01].
Conclusions
LOR (0.07 mg) demonstrated improved PRO threshold responses across single and composite measures of pain, function, and patient global assessment compared with PBO, with benefits sustained to 24 weeks.
Plain Language Summary
Lorecivivint (LOR) is a new injectable medicine being studied as a treatment for knee osteoarthritis (OA). An early (phase 2b) trial found participants with moderate-to-severe knee OA receiving LOR on average reported improved pain, function, and reduced impact of OA symptoms over 24 weeks compared with placebo. To consider how likely individuals were to respond to treatment, this study analyzed how many participants per group achieved different percentage levels of symptom improvement. Participants were given a single LOR or placebo injection into their most painful (target) knee at trial initiation. Participants reported their target knee status from day 1 (baseline) to week 24 using pain and function questionnaires. We analyzed the number of participants given 0.07 mg LOR and placebo whose symptom scores improved by 30, 50, and 70% over baseline scores at weeks 12 and 24. Results showed that 0.07 mg LOR treatment produced a higher likelihood beyond chance at week 12 of achieving a 30% improvement in some pain and function scores and a 50% improvement in other symptom scores compared with placebo. Similar 30% and 50% symptom score improvements were found at week 24. More complex scores, combining individual symptom scores into single index measures, also showed improvements beyond chance for 0.07 mg LOR from baseline compared with placebo at weeks 12 and 24. Thus, more participants with knee OA who were treated with 0.07 mg LOR demonstrated long-lasting, meaningful improvements in pain and function compared to those given placebo.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2021. 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/bync/ 4.0/. |
Keywords: | Alternative splicing; CLK2; DYRK1A; OMERACT-OARSI; Patient-reported outcomes; Wnt signaling pathway |
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: | 19 May 2021 13:29 |
Last Modified: | 14 Sep 2023 13:47 |
Published Version: | https://link.springer.com/article/10.1007/s40744-0... |
Status: | Published |
Publisher: | Springer |
Identification Number: | 10.1007/s40744-021-00316-w |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:174258 |