Peripheral Nerve Safety of Nerve Growth Factor Inhibition by Tanezumab: Pooled Analyses of Phase III Clinical Studies in Over 5000 Patients with Osteoarthritis.

Abstract

Tanezumab, a humanized anti-nerve growth factor antibody, was developed for the treatment of pain associated with osteoarthritis. Due to its mechanism of action, peripheral nerve safety was assessed in all clinical studies. To summarize the neurological safety of intravenous (IV) and subcutaneous (SC) tanezumab versus placebo in patients with osteoarthritis. Data were pooled from 3389 patients across seven studies that investigated IV administration, and from 1840 patients across three studies that investigated SC administration. The treatment period of each study ranged from 16 to 24weeks, and follow-up periods ranged from 8 to 24weeks. Neurological safety evaluations focused on adverse events (AEs) of abnormal peripheral sensation (APS), neurologic examinations, and consultations. Across datasets, the incidence of AEs of APS was higher in tanezumab groups versus placebo. Paresthesia and hypoesthesia were the most frequently reported AEs in tanezumab-treated patients, compared with placebo. In both datasets, most AEs were of mild severity, resolved, and rarely resulted in discontinuation. In all treatment groups in both IV and SC studies, over 90% of patients had no new or worsened neurological examination abnormalities at the last study visit. Across datasets, mononeuropathy was diagnosed more frequently in tanezumab groups compared with placebo. Polyneuropathy was diagnosed in ≤ 0.9% of patients in tanezumab and placebo groups. Tanezumab IV or SC had an increased incidence of AEs of APS, such as paresthesia and hypoesthesia, and diagnoses of mononeuropathy compared with placebo. However, tanezumab was not associated with generalized peripheral neuropathy. NCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00863772, NCT01089725, NCT00985621, NCT02697773, and NCT02709486.