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A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain.

Lascelles BD, Knazovicky D, Case B, Freire M, Innes JF, Drew AC, Gearing DP - BMC Vet. Res. (2015)

Bottom Line: 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).The magnitude of the effect appeared identical to that expected with an NSAID.

View Article: PubMed Central - PubMed

Affiliation: Comparative Pain Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. duncan_lascelles@ncsu.edu.

ABSTRACT

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.

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Related in: MedlinePlus

Graph of mean change (week 4 minus baseline) in activity count per minute for each hour of the day in the NV-01 group (dotted line) and the placebo group (solid line).
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Fig4: Graph of mean change (week 4 minus baseline) in activity count per minute for each hour of the day in the NV-01 group (dotted line) and the placebo group (solid line).

Mentions: The mean activity over 24 hours during the baseline period (Days -7 to -1) is shown in Figure 3. Using the average activity per minute over the baseline and final week (Days 20-27), activity in the NV-01 group increased over the duration of the study (significant on 1-sided t-test, P = 0.045; significant at the 10% level on 2-sided t-test, P = 0.090). Activity in dogs in the placebo group did not change over the duration of the study (1-sided t-test, P = 0.810; 2-sided t-test, P = 0.379). The difference between the groups for change in average activity was significant at the 10% level (P = 0.063, 2-sided t-test), but not at the critical p-value (0.05) set a priori before the study initiated. Figure 4 illustrates the change (final week minus baseline) in mean activity per minute over 24 hours. The difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant, with the NV-01 group being more active than the placebo group (P = 0.006).Figure 3


A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain.

Lascelles BD, Knazovicky D, Case B, Freire M, Innes JF, Drew AC, Gearing DP - BMC Vet. Res. (2015)

Graph of mean change (week 4 minus baseline) in activity count per minute for each hour of the day in the NV-01 group (dotted line) and the placebo group (solid line).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4419463&req=5

Fig4: Graph of mean change (week 4 minus baseline) in activity count per minute for each hour of the day in the NV-01 group (dotted line) and the placebo group (solid line).
Mentions: The mean activity over 24 hours during the baseline period (Days -7 to -1) is shown in Figure 3. Using the average activity per minute over the baseline and final week (Days 20-27), activity in the NV-01 group increased over the duration of the study (significant on 1-sided t-test, P = 0.045; significant at the 10% level on 2-sided t-test, P = 0.090). Activity in dogs in the placebo group did not change over the duration of the study (1-sided t-test, P = 0.810; 2-sided t-test, P = 0.379). The difference between the groups for change in average activity was significant at the 10% level (P = 0.063, 2-sided t-test), but not at the critical p-value (0.05) set a priori before the study initiated. Figure 4 illustrates the change (final week minus baseline) in mean activity per minute over 24 hours. The difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant, with the NV-01 group being more active than the placebo group (P = 0.006).Figure 3

Bottom Line: 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).The magnitude of the effect appeared identical to that expected with an NSAID.

View Article: PubMed Central - PubMed

Affiliation: Comparative Pain Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. duncan_lascelles@ncsu.edu.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus