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.