A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain.
BACKGROUND
There is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups.


RESULTS
CBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006).


CONCLUSIONS
These pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.
Comparative Pain Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. duncan_lascelles@ncsu.edu.|Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. duncan_lascelles@ncsu.edu.|Center for Pain Research and Innovation, UNC School of Dentistry, Chapel Hill, NC, USA. duncan_lascelles@ncsu.edu.
B Duncan X
BD
Lascelles
Comparative Pain Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. david_knazovicky@ncsu.edu.
David
D
Knazovicky
Comparative Pain Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. bcc@ncsu.edu.
Beth
B
Case
Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada. m.freire.gonzalez@umontreal.ca.
Mila
M
Freire
ChesterGates Referral Hospital, Chester, UK. john.innes@cvsvets.com.
John F
JF
Innes
Nexvet Australia Pty Ltd, Melbourne, VIC, Australia. alec.drew@nexvet.com.
Alexander C
AC
Drew
Nexvet Australia Pty Ltd, Melbourne, VIC, Australia. dave.gearing@nexvet.com.
David P
DP
Gearing
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D004311:Double-Blind Method; D005260:Female; D007167:Immunotherapy / Q000662:veterinary*; D008297:Male; D020932:Nerve Growth Factor / Q000276:immunology*; D010003:Osteoarthritis / Q000628:therapy / Q000662:veterinary*; D010146:Pain / Q000188:drug therapy / Q000662:veterinary*
D000906:Antibodies; D020932:Nerve Growth Factor