A randomized clinical efficacy study targeting mPGES1 or EP4 in dogs with spontaneous osteoarthritis.

Abstract

Canine studies of spontaneous osteoarthritis (OA) pain add valuable data supporting drug treatment mechanisms that may translate to humans. A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in client-owned dogs with moderate OA pain to evaluate efficacy of LYA, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES1), an EP4 antagonist (LYB), and carprofen, versus placebo. Of 255 dogs screened, 163 were randomized (placebo/LYA/LYB/carprofen: n = 43/39/42/39) and 158 completed treatment. Efficacy versus placebo was assessed using Bayesian mixed-effect model for repeated measure analyses of the Canine Brief Pain Inventory (CBPI) pain interference score (PIS; primary endpoint), pain severity score, and overall impression, as well as the Liverpool Osteoarthritis in Dogs (LOAD) mobility score. The posterior probability that the difference to placebo was <0 at week 2 was 80% for LYA and 54% for LYB for CBPI PIS (both <95% predefined threshold). For secondary endpoints, the posterior probability that the difference to placebo was <0 at week 2 ranged from 89 to 96% for LYA and from 56 to 89% for LYB. The posterior probabilities comparing carprofen to placebo groups were ≥90% for all efficacy endpoints. The proportion of dogs with one or more adverse event was not significantly different from placebo (32.6%) for LYA (35.9%) or carprofen (25.6%), but the rate for LYB (59.5%) was higher versus placebo (P = 0.017). LYA treatment demonstrated consistent improvement in all efficacy measures, suggesting that inhibition of mPGES1 may be an effective treatment for chronic pain associated with OA.

• Authors: Carol Robertson-Plouch, John R Stille, Peng Liu, Claire Smith, Dorothy Brown, Margaret Warner, Leijun Hu, Matthew J Fisher
• Journal: Science translational medicine (Sci Transl Med) Vol. 11 Issue 516 (10 30 2019) ISSN: 1946-6242 [Electronic] United States
• PMID: 31666405 (Publication Type: Journal Article, Randomized Controlled Trial, Veterinary, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Placebos
• Receptors, Prostaglandin E, EP4 Subtype
• Prostaglandin-E Synthases

Topics

• Animals
• Dogs
• Endpoint Determination
• Female
• Follow-Up Studies
• Male
• Osteoarthritis (drug therapy, veterinary)
• Placebos
• Probability
• Prostaglandin-E Synthases (antagonists & inhibitors, metabolism)
• Receptors, Prostaglandin E, EP4 Subtype (antagonists & inhibitors, metabolism)
• Treatment Outcome