A Feline‐Specific Anti‐Nerve Growth Factor Antibody Improves Mobility in Cats with Degenerative Joint Disease–Associated Pain: A Pilot Proof of Concept Study

Abstract

BackgroundNeutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans.ObjectivesTo evaluate the efficacy of a fully felinized anti‐NGF antibody (NV‐02) for the treatment of DJD pain and mobility impairment in cats.AnimalsThirty‐four client‐owned cats with DJD‐associated pain and mobility impairment.MethodsIn a placebo‐controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV‐02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client‐specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated‐measures model was used to evaluate the objective activity data.Results NV‐02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment‐related adverse effects were identified.ConclusionsThese pilot data demonstrate a 6‐week duration positive analgesic effect of this fully felinized anti‐NGF antibody in cats suffering from DJD‐associated pain.

Anti–nerve growth factor therapy increases spontaneous day/night activity in mice with orthopedic surgery–induced pain

“…Spontaneous movement has been validated and successfully used as an outcome measure in cat [26; 27] and dog [11-14; 61; 78; 80] spontaneous models of chronic OA musculoskeletal pain, and it is well established that activity is an important measure of musculoskeletal pain-associated disability in humans [9; 35; 43; 58; 73]. Similarly, with skeletal pain following orthopedic surgery, our data indicate that mice show a marked reduction in levels of spontaneous movement and rearing and thus have significantly reduced “functional status” compared to their non-operated controls.…”

“…Previous studies in humans with osteoarthritis and low back pain showed that anti-NGF reduced these skeletal pains by 40% and 30% respectively [40; 45], and dramatic improvement in function and activity was seen in cat [27] and dog [47] spontaneous OA models following administration of anti-NGF. In the present study, during the times the animals were most active, anti-NGF increased horizontal activity, velocity and vertical rearing but had no effect in increasing activity or rearing when the mice were normally less active.…”

The Use of Functional Data Analysis to Evaluate Activity in a Spontaneous Model of Degenerative Joint Disease Associated Pain in Cats

“…Inclusion criteria for the intervention trials have been previously described [25, 30, 50]. Briefly, cats were required to be greater than one year of age and weigh more than one kg, and to have a qualifying degree of owner-rated mobility impairment, joint pain on orthopedic examination, and radiographic evidence of DJD.…”

“…Exclusion criteria, common across trials, have been described previously [25, 30, 50] and included the presence of suspected or diagnosed infectious diseases, symptomatic cardiac disease, immune-mediated disease, neoplasia, inflammatory bowel disease, urinary tract infection, hyperthyroidism, and diabetes mellitus. Cats with stable chronic kidney disease (CKD) up to and including IRIS stage two [51] were eligible to enroll following demonstration of stable serum biochemistry and urinalysis results.…”

Session 10: Anaesthesia and Pain Control

“…The analgesic efficacy of anti-nerve growth factor (anti-NGF) monoclonal antibodies (mAbs) for the treatment of DJD-relate pain has been recently reported in cats (7). These are species-specific Ab targeting NGF which has an important role in pro-nociception.…”