Efficacy and safety of enflicoxib for treatment of canine osteoarthritis: A 6‐week randomised, controlled, blind, multicentre clinical trial

Abstract

Background: Enflicoxib is a new COX-2 selective NSAID intended for the treatment of pain and inflammation associated with canine osteoarthritis. Methods: A prospective, multisite, blinded, randomised, controlled, parallelgroup field study was performed to determine the efficacy and safety of enflicoxib in canine osteoarthritis. A total of 242 dogs were randomised to receive enflicoxib at 4 or 2 mg/kg, mavacoxib at 2 mg/kg or placebo, orally. Enflicoxib and placebo were administered once weekly from day 0 to day 35. Mavacoxib was administered on D0 and day 14. Veterinarians assessed efficacy with a numerical rating scale and owners used the Canine Brief Pain Inventory. Results: After 6 weeks, enflicoxib at 4 mg/kg showed the highest percentage of responders as assessed by the veterinarians (68%) and the owners (84%), followed by mavacoxib (62and 83%, respectively), and enflicoxib at 2 mg/kg (57 and 80%, respectively). All treatments reached statistical significance versus placebo, which obtained success rates of 37% and 53%, respectively. No differences in the incidence of adverse reactions were detected among the different groups. Conclusions: Enflicoxib administered weekly for 6 weeks, at 4 mg/kg PO with an initial loading dose of 8 mg/kg, is efficacious and safe for the treatment of canine osteoarthritis.

Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib

“…These results confirm the findings of Salichs et al [ 37 ], in which a tendency for a faster onset of action was also observed for enflicoxib following the same treatment schedule. The efficacy obtained in the mavacoxib group was somewhat lower than previously described by Payne-Johnson et al [ 42 ], were mavacoxib treated dogs showed an overall improvement of 93.4% for the owner assessment and similar results for the veterinary assessment.…”

“…The veterinarians assessed pain and lameness using NRS as described by several authors [ 39 – 43 ]. This NRS included the assessment of four parameters in the following order: posture while the dog was standing, lameness at walk, lameness at trot and pain at palpation/manipulation of the affected joint as described in Salichs et al [ 37 ]. A factor of two was applied to place more weight on lameness at walk and at trot as part of the clinical picture of OA [ 39 , 40 , 43 ].…”

“…The Per Protocol (PP) population included dogs that were fully compliant with the protocol except for cases with minor deviations that would not affect the results. As the severity of the disease at the time of enrolment can negatively affect the efficacy outcomes [ 37 ], further statistical analyses were carried out on a subset of the PP population including only dogs with initial CSS≥8 to assess the effect of treatment in dogs with more severe clinical signs of OA.…”

“…In a previous clinical study, enflicoxib has shown to be superior to a placebo, with a good safety profile, at a dose of 4 mg/kg, once a week, with an initial loading dose of 8 mg/kg [ 37 ]. The present study follows very similar procedures to the former one with the objective to confirm the clinical relevance of the selected enflicoxib dose, by demonstrating non-inferiority to an approved and effective NSAID for the treatment of canine OA (mavacoxib, Trocoxil®, Zoetis) that is used as reference product.…”

Selective inhibition of cyclooxygenase‐2 by enflicoxib, its enantiomers and its main metabolites in vitro in canine blood

“…Importantly, the efficacy of such concentrations was demonstrated in clinical studies at the recommended dose and even at half the recommended dose (Salichs et al, 2021 ). It is also worth noting that the pharmacological effect of enflicoxib treatment could be based not only on a direct effect on enzymatic COX‐2 activity but also on COX‐independent immunosuppressant and anti‐inflammatory actions shared by parent and main metabolite.…”