Evaluation of clinical effects and plasma metabolomic profiles after the administration of grapiprant in dogs affected by osteoarthritis: a prospective, off-on-off, clinical study.

Introduction: Osteoarthritis (OA) is a prevalent cause of chronic pain and impaired mobility in dogs. Grapiprant, an EP4 prostaglandin receptor antagonist, represents a novel therapeutic option with a favorable safety profile compared to traditional NSAIDs. Aim: To evaluate the clinical efficacy of grapiprant in dogs with naturally occurring OA and to investigate systemic metabolomic changes using proton nuclear magnetic resonance ( Methods: Thirty-six dogs with mild to moderate OA were enrolled in a prospective off-on-off study (30 days pre-treatment, 60 days grapiprant treatment at 2 mg/kg, 30 days post-treatment). Outcomes included owner questionnaires (LOAD, CBPI), pressure-sensitive walkway gait analysis (GLS), orthopedic evaluation, and plasma metabolomics. Results: Grapiprant significantly reduced LOAD scores at T30 and T60 compared with baseline (* Conclusion: Grapiprant improved mobility and pain control in dogs with OA and induced metabolomic shifts consistent with reduced inflammation and improved energy metabolism. This is the first study to integrate clinical outcomes with metabolomics in canine OA, supporting the translational value of metabolic biomarkers for monitoring therapeutic response.