A randomised, parallel group clinical trial comparing bedinvetmab to meloxicam for the management of canine osteoarthritis

John Francis Innes ^1,2* B. Duncan X. Lascelles ^3,4 Daniel Bell ⁵ Robert Tulloch ⁶ Alex Mcvey ⁷ Chad Northcott ⁸ Mahala Welbourn ⁹ Kate Higgins ¹⁰ Veronika Horakova ¹¹ Thomas Maddox ²

• ¹ Consultant, Movement referrals: Independent Veterinary Specialists, United Kingdom
• ² Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Leahurst Campus, Neston, United Kingdom
• ³ Translational Research in Pain Program, North Carolina State University, Raleigh, United States
• ⁴ Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States
• ⁵ The Sands Veterinary Practice, Apex House, Kelsall Rd, Tarvin Sands, Chester, United Kingdom
• ⁶ 6 The Market Town Vet, 3D Church St, Oswestry, United Kingdom
• ⁷ Woolton Veterinary Centre, 65 Quarry St, Liverpool, Liverpool, United Kingdom
• ⁸ Vetcare Ltd., Newlands Rd, Leigh, Leigh, United Kingdom
• ⁹ Wigan Vets for Pets, 296B Woodhouse Lane, Wigan, United Kingdom
• ¹⁰ The Village Veterinary Surgery, 1 Brows Lane, Formby, United Kingdom
• ¹¹ Hollybank Veterinary Centre Ltd, 584 Chester Road, Sandiway, Cheshire, United Kingdom

Objective: Bedinvetmab (Librela®), a fully canine anti-nerve growth factor monoclonal antibody, was compared to the non-steroidal anti-inflammatory drug (NSAID), meloxicam, in dogs for management of osteoarthritis-related pain in a randomised, open-label, multicentre, parallel-group study. Subjects were recruited from general practice client-owned dogs with appendicular osteoarthritis. Dogs were block randomized 1:1 to daily oral meloxicam or bedinvetmab administered subcutaneously once monthly. The primary end point for efficacy was change from baseline Canine Orthopedic Index (COI) score'. Linear mixed effect models were used for statistical analysis conducted on a per protocol and intent to treat basis. We hypothesised that bedinvetmab would have superior efficacy and safety compared to meloxicam; number needed to harm (NNH) for meloxicam, relative to bedinvetmab, was calculated. Of 190 screened dogs, 101 were randomised (bedinvetmab 52; meloxicam 49). Overall, both treatment groups showed a significant reduction in COI scores relative to baseline (P<0.001). The bedinvetmab group had a larger mean reduction in COI scores but this was not statistically significant. There was a significant effect of visit, with later visits showing a significantly greater reduction in COI compared to Visit 2 (P<0.001). For safety, there was a significant effect of treatment, with bedinvetmab showing a reduction in the likelihood of an adverse event [Odds Ratio 0.291; 95% Confidence Interval (0.135-0.627); P=0.002] compared to meloxicam. The bedinvetmab group had 4 adverse events compared to 17 in the meloxicam group, 9 of which were gastrointestinal system disorders. Bedinvetmab also had more dogs complete the study (n=44) vs meloxicam (n=33). This is the first study to compare bedinvetmab to a NSAID for the management of osteoarthritis-related pain in dogs. The results indicate both products are equally effective in managing OA pain, and efficacy improved with both products over time. Bedinvetmab was associated with significantly fewer adverse events. These data will assist clinicians and pet owners when deciding on analgesic options for dogs with osteoarthritis.