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

Abstract

Background This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42. Results The overall CSS expressed as area under the curve demonstrated non-inferiority of enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of enflicoxib versus mavacoxib was confirmed. The dog’s quality of life improved in all groups, but only enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment. Conclusions Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.

A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs

“…Further to the exclusion criteria related to non-permitted antiinflammatory and analgesic previous medication or disease modifying and chondroprotective agents or diets as well as concomitant diseases and the concomitant treatment administration restrictions included in previous efficacy clinical trials with enflicoxib (8,9), dogs could not have received intra-articular injections of any type for 1 year and depot anti-inflammatory drugs for at least 120 days.…”

“…Several reasons for withdrawal of dogs from the study were applicable as previously described (8,9). For cases withdrawn due to worsening of clinical signs of OA or unsatisfactory therapeutic response, additional veterinary care including rescue therapy was permitted after withdrawal of the dog from the study.…”

“…Safety criteria included the clinical signs, severity, causality evaluation and incidence calculations. Adverse events description, recording and assessment was performed as previously described (8,9) and following the Veterinary Dictionary for Drug Regulatory Activities (VeDDRA) terms (20) and the ABON system of causality assessment (20). This assessment considered that NSAIDs have the potential to cause or exacerbate gastrointestinal, renal, and hepatic disorders.…”

“…From the efficacy point of view, considering that previous experience describes a placebo effect of 30% (8,9), and the desired proportion 3:1 of dogs in enflicoxib and placebo groups, a sample size of 60 and 20 dogs would be required, respectively. This sample size would provide 90% power to detect differences in the primary efficacy endpoint with a 0.05 two-sided significance level (Chi-Square test).…”

“…Enflicoxib, a recently launched NSAID of the coxib class, is dosed at weekly intervals, with an initial loading dose of 8 mg/kg, followed by once weekly doses of 4 mg/kg (Daxocox ® tablets for dogs, Ecuphar/ Animalcare group) (5). Enflicoxib has shown to be efficacious and safe in various laboratory models of pain and inflammation (6), in arthritis models in dogs (7), and in randomized field clinical studies in dogs with naturally occurring OA over a 6-week treatment period (8,9).…”