Photo Credit: TefiM

The following is a summary of “Impact of Structural Severity on Outcomes in Knee Osteoarthritis: An Analysis of Data from Phase 2 and Phase 3 Lorecivivint Clinical Trials,” published in the November 2024 issue of Rheumatology by Tambiah et al. 

Knee osteoarthritis treatments are challenging due to pain and joint structure variability. Lorecivivint (LOR) is an intra-articular CLK/DYRK inhibitor targeting Wnt and inflammatory pathways. 

Researchers conducted a retrospective study to analyze baseline joint structure’s impact on pain response in knee osteoarthritis using LOR 0.07 mg data. 

They enrolled patients with knee osteoarthritis from 2 Phase 2 and 2 Phase 3 trials with Kellgren-Lawrence (KL) Grades 2–3 and Pain Numeric Rating Scale (NRS [0–10]) scores between 4 and 8 in the target knee. Cumulative frequency distribution plots by KL grade showed percentages of patients with medial joint space width (medial JSW) < 3 mm. They summarized Osteoarthritis Research Society International Joint Space Narrowing grades and treatment responses in trials measuring Pain NRS. They estimated pain outcome changes using baseline-adjusted ANCOVA. 

The results showed that Phase 3 trials had more patients with baseline medial JSW < 3 mm. LOR showed better treatment effects than placebo in KL 2 subgroups with higher baseline medial JSW > 3 mm, except in 1 Phase 3 trial with advanced knee OA. 

The study concluded that LOR showed greater symptomatic improvements in patients with less advanced structural disease, suggesting early treatment may improve outcomes and inform future OA trial criteria. 

Source: academic.oup.com/rheumatology/advance-article-abstract/doi/10.1093/rheumatology/keae610/7874973