Neurological safety of subcutaneous tanezumab versus NSAID in patients with osteoarthritis
Mark T Brown, Paola Sandroni, Phillip A Low, Kenneth C Gorson, David J Hunter, Glenn C Pixton, Robert J Fountaine, Lars Viktrup, Christine R West, Kenneth M Verburg, Mark T Brown, Paola Sandroni, Phillip A Low, Kenneth C Gorson, David J Hunter, Glenn C Pixton, Robert J Fountaine, Lars Viktrup, Christine R West, Kenneth M Verburg
Abstract
Objective: To assess the long-term neurological safety of tanezumab, a monoclonal antibody against nerve growth factor.
Methods: Patients with osteoarthritis of the hip or knee received stable doses of oral nonsteroidal anti-inflammatory drugs (NSAIDs) before study entry and during a ≤ 37-day screening period. Patients were randomized 1:1:1 to double-dummy tanezumab (2.5 mg or 5 mg, subcutaneous every 8 weeks) or oral NSAIDs (twice-daily) for 56 weeks, with a 24-week follow-up. Neurological safety evaluation focused on peripheral and sympathetic adverse events (AEs), neurologic examinations, and consultations with blinded, external diagnostic reviews.
Results: During the treatment period, 6.2%, 9.0%, and 4.6% of patients experienced AEs of abnormal peripheral sensation (APS) in the tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. Hypoesthesia, paresthesia, and carpal tunnel syndrome were the most common AEs of APS. Clinically significant worsening on examination occurred in <1% in any treatment group at the last study assessment. Diagnoses following external neurological consultation included mononeuropathy (1.3%, 2.1%, and 1.0%), radiculopathy (0.9%, 0.4%, and 0.5%), and polyneuropathy (0.3%, 0.5%, and 0%) in tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. AEs potentially associated with sympathetic neuropathy were reported for 1.8%, 2.3%, and 2.9% of patients in the tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. No patient was diagnosed with sympathetic neuropathy.
Conclusion: Tanezumab had an increased incidence of AEs of APS versus NSAID; these were typically mild/moderate in severity, resolved during the study, and rarely resulted in discontinuation. Tanezumab was not associated with peripheral neuropathy and did not adversely affect the sympathetic nervous system.
Trial registration: ClinicalTrials.gov Identifier NCT02528188 (https://ichgcp.net/clinical-trials-registry/NCT02528188).
Keywords: NSAID; Nerve growth factor; Neurological safety; Osteoarthritis; Tanezumab.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Source: PubMed