A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee

Abstract

Tanezumab is a humanized monoclonal antinerve growth factor antibody in development for treatment of chronic pain. In a phase III, placebo- and active-controlled study, we investigated the efficacy and safety of tanezumab for osteoarthritis (OA) hip or knee pain. Patients (N=610) received up to 2 doses of intravenous tanezumab (5 or 10mg in 8-week intervals), controlled-release oral oxycodone (10 to 40 mg every 12 hours), or placebo. The primary endpoint was mean change from baseline to week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain score for tanezumab versus placebo and oxycodone. Secondary endpoints included change from baseline in WOMAC Physical Function and Stiffness scores, Patient's Global Assessment (PGA) of OA, and patient response, defined as ≥ 30%, ≥ 50%, ≥ 70%, and ≥ 90% improvement from baseline in WOMAC Pain score. Tolerability and safety also were assessed. Both tanezumab groups demonstrated significant improvements in WOMAC Pain score versus placebo (P<.001) and oxycodone (P ≤.018). Tanezumab also provided significant improvements versus placebo and oxycodone for WOMAC Physical Function and Stiffness scores and PGA of OA (P ≤.002 for all) at week 8. For all analyses, oxycodone did not differ from placebo. Adverse event frequency was higher with oxycodone (63.3%) than tanezumab (40.7% to 44.7%) or placebo (35.5%); serious adverse event frequency was similar among treatments. The adverse event profile for tanezumab was similar to previous tanezumab studies. Results indicate that tanezumab is efficacious in the treatment of OA pain; no new safety signals were identified.

Update on biological therapies for knee injuries: osteoarthritis

“…Currently, there are no approved biological therapies for patients with OA. Recent studies showed significant improvement in pain and function of knee OA with tanezumab; however, it should be mentioned that mild to moderate AEs occurred [32][33][34][35].…”

“…During the neonatal period, NGF supports development of the sensory neurons; in adults, NGF is essential in raising awareness of the nociceptor function of neurons with the onset of pain and hyperalgesia in chronic pain. This function may be observed after injury and inflammation, when NGF expression ultimately increases, including in patients with OA, who also express high levels of NGF in their joints [32][33][34][35].…”

“…In another phase III randomized controlled trial, Spierings et al [33] investigated the efficacy and safety of tanezumab for hip and knee OA. A total of 660 patients were assigned to receive intravenous tanezumab (5 or 10 mg in 8-week intervals), oral controlled-release oxycodone (10-40 mg every 12 hours), or placebo.…”

Pain and Inflammation. Part 2. The Analgesic Potential of Anti-Inflammatory Drugs

“…Однако проведенные исследования, к сожале-нию, обнаружили и ряд недостатков танезумаба, кото-рые в итоге приостановили его регистрацию и начало применения в реальной практике. Оказалось, что новое лекарство вызывает серьезные НР -появление сенсор-ных симптомов (парестезия и гипестезия), в ряде случа-ев появление или ухудшение полиневропатии, а также ускорение прогрессирования ОА, которое в отдельных случаях потребовало проведения эндопротезирования [61][62][63].…”

Dissatisfaction with management of musculoskeletal pain: A global problem and methods of its solution

“…Но в этих работах выявлен и ряд недостатков танезумаба, что в итоге приостановило его регистрацию и начало применения в реальной практике. Это серьезные НР: появление сенсор-ных симптомов (парестезия и гипестезия), в некоторых слу-чаях развитие полиневропатии, а также ускорение прогрес-сирования ОА, которое у отдельных пациентов потребовало выполнения эндопротезирования [35][36][37].…”