Neurological safety of subcutaneous tanezumab versus NSAID in patients with osteoarthritis

J Neurol Sci. 2022 Mar 15:434:120184. doi: 10.1016/j.jns.2022.120184. Epub 2022 Feb 14.

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://clinicaltrials.gov/ct2/show/NCT02528188).

Keywords: NSAID; Nerve growth factor; Neurological safety; Osteoarthritis; Tanezumab.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Double-Blind Method
  • Humans
  • Osteoarthritis, Hip* / complications
  • Osteoarthritis, Hip* / drug therapy
  • Osteoarthritis, Knee* / complications
  • Osteoarthritis, Knee* / drug therapy
  • Pain Measurement / methods
  • Paresthesia / complications
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal, Humanized
  • tanezumab

Associated data

  • ClinicalTrials.gov/NCT02528188