title: Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment.
abstract: To evaluate peripheral nerve safety and clinical efficacy of tanezumab in patients with painful osteoarthritis.
  
  
  
  Patients received intravenous tanezumab 5mg, tanezumab 10mg, or placebo every 8 weeks for 24 weeks. Neurological safety was evaluated via a composite score (nerve conduction attributes and heart rate variability with deep breathing; Σ5NC + HRdb), intraepidermal nerve fiber (IENF) density, and clinical assessments. Efficacy and general safety were also evaluated.
  
  
  
  The study was stopped prematurely by an FDA partial clinical hold (joint safety issues in other studies). Differences in change from baseline to Week 24 in Σ5NC + HRdb were not significant. Tanezumab 5mg vs placebo exceeded the prespecified clinically important difference using last observation carried forward imputation, but not with observed data or when patients with evidence of neuropathy at baseline were excluded. No significant differences were found in individual nerve conduction measures. No treatment exceeded the prespecified clinically important decrease in IENF. Tanezumab resulted in significant improvement in pain, physical function, and Patient's Global Assessment. Safety was similar to previous tanezumab clinical trials.
  
  
  
  Tanezumab has a modulating effect on pain, does not appear to increase neurological safety signals, and offers a potentially promising, novel approach in treatment of pain.
authors: Pfizer Inc., Groton, CT, USA. Electronic address: mark.t.brown@pfizer.com.
authors: Mark T
authors: MT
authors: Brown
authors: University of Rochester, Rochester, NY, USA.
authors: David N
authors: DN
authors: Herrmann
authors: Medical Specialists of the Palm Beaches, Inc., Atlantis, FL, USA.
authors: Mark
authors: M
authors: Goldstein
authors: Pfizer Inc., Groton, CT, USA.
authors: Aimee M
authors: AM
authors: Burr
authors: Pfizer Inc., Groton, CT, USA.
authors: Michael D
authors: MD
authors: Smith
authors: Pfizer Inc., Groton, CT, USA.
authors: Christine R
authors: CR
authors: West
authors: Pfizer Inc., Groton, CT, USA.
authors: Kenneth M
authors: KM
authors: Verburg
authors: Mayo Clinic, Rochester, MN, USA.
authors: Peter J
authors: PJ
authors: Dyck
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors*; D009431:Neural Conduction / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D020932:Nerve Growth Factor; C549319:tanezumab
keywords: Intraepidermal nerve fiber density; Nerve growth factor; Neurological safety; Osteoarthritis; Pain; [limit 6] Tanezumab