Objective: To evaluate peripheral nerve safety and clinical efficacy of tanezumab in patients with painful osteoarthritis.
Methods: 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.
Results: 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.
Conclusions: 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.
Trial registration: ClinicalTrials.gov NCT00863772.
Keywords: Intraepidermal nerve fiber density; Nerve growth factor; Neurological safety; Osteoarthritis; Pain; [limit 6] Tanezumab.
Copyright © 2014 Elsevier B.V. All rights reserved.