Premium
General Safety and Tolerability of Subcutaneous Tanezumab for Osteoarthritis: A Pooled Analysis of Three Randomized, Placebo‐Controlled Trials
Author(s) -
Berenbaum Francis,
Schnitzer Thomas J.,
Kivitz Alan J.,
Viktrup Lars,
Hickman Anne,
Pixton Glenn,
Brown Mark T.,
Davig Isabelle,
West Christine R.
Publication year - 2022
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.24637
Subject(s) - placebo , tolerability , medicine , osteoarthritis , discontinuation , orthostatic vital signs , adverse effect , surgery , blood pressure , pathology , alternative medicine
Objective This pooled analysis of 3 randomized, placebo‐controlled trials (16–24 week treatment and 8–24 week follow‐up) assessed safety of subcutaneous tanezumab (2.5–10 mg every 8 weeks) in 1,840 patients with hip or knee osteoarthritis. Methods Overall treatment‐emergent adverse events (TEAEs) and TEAEs of abnormal peripheral sensation (APS) were prospectively assessed in 3 trials. Joint safety events (primary osteonecrosis, rapidly progressive osteoarthritis [RPOA], subchondral insufficiency fracture, and pathologic fracture; adjudicated by an independent expert committee) and TEAEs potentially associated with sympathetic neuropathy were prospectively assessed in 2 trials. Results During the treatment period, overall TEAE rates were 51.7% for placebo and 39.5–54.8% for tanezumab 2.5–10 mg; treatment discontinuation rates were 2.0% for placebo and 0–1.3% for tanezumab. Rates of composite joint safety events (predominantly RPOA type 1) over the treatment plus follow‐up period were 0% for placebo and 0.5–3.2% for tanezumab 2.5–5 mg (5 mg was statistically greater than placebo); total joint replacement rates with tanezumab (5.9–7.0%) were not significantly different from placebo (4.5%). Rates of TEAEs of APS (predominantly paresthesia and hypoesthesia) were 2.2% for placebo and 3.2–12.8% for tanezumab 2.5–10 mg. Rates of TEAEs potentially associated with sympathetic neuropathy (predominantly bradycardia and orthostatic hypotension) were 0.8% for placebo and 0.5–2.8% for tanezumab 2.5–5 mg (exposure‐adjusted rates were not significantly different from placebo). Conclusion Tanezumab was generally well tolerated. TEAEs of APS (mostly mild and transient) and joint safety events were infrequent but more common with tanezumab than placebo. A tanezumab dose of 2.5 mg demonstrated a more favorable safety profile than higher doses.