Patients with osteoarthritis (OA) of the hip or knee may benefit from tanezumab, according to a new randomized, double-blind, placebo-controlled study.
“Nerve growth factor (NGF) is a neurotrophin involved in pain signaling and nociceptor gene expression,” the researchers reported in JAMA. “NGF has been shown to contribute to the clinical symptom of pain hypersensitivity, which is often seen during inflammation and chronic pain conditions. NGF is expressed in the subchondral bone of patients with osteoarthritis (OA),7 consistent with a role in symptomatic OA pain.” Tanezumab works by inhibiting NGF binding to its receptors.
The researchers sought to determine tanezumab’s efficacy and any adverse events (AEs) related to its use in patients with moderate to severe OA who were unresponsive to standard pharmacological OA treatments.
The study—conducted between January 2016 and May 2018 and spanning 89 sites in the United States, Canada, and Puerto Rico—included a 16-week treatment period and a 24-week follow-up period. Patients aged ≥ 18 years with a diagnosis of hip or knee OA were eligible for inclusion based on the following criteria:
- Index joint Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain subscale score ≥ 5 at screening and baseline
- WOMAC Physical Function subscale score ≥ 5 at baseline
- Patient global assessment of osteoarthritis (PGA-OA) rating of fair, poor, or very poor at baseline
- Insufficient pain relief from acetaminophen
- Insufficient pain relief, intolerance to, or contraindication to NSAIDs
- Insufficient pain relief, intolerance to, or contraindication to either tramadol or opioids
Tanezumab was administered for 16 weeks either in fixed dosing (2.5 mg administered at baseline and week 8) or forced dose titration (2.5 mg administered at baseline and 5 mg at week 8); both regimens were compared to placebo. The main outcome was the comparison between tanezumab and placebo.
Out of 698 randomized patients, 582 completed the trial. Baseline mean WOMAC Pain scores were 7.1 in the 2.5 mg tanezumab group, 7.3 in the 2.5/5 mg tanezumab group, and 7.3 in the placebo group; after 16 weeks, the scores decreased to 3.6, 3.6, and 4.4, respectively. Baseline mean WOMAC Physical Function scores were 7.2 in the 2.5 mg tanezumab group, 7.4 in the 2.5/5 mg tanezumab group, and 7.4 in the placebo group, and decreased to 3.7, 3.6, and 4.5 respectively. The baseline mean PGA-OA scores were 3.4, 3.5, and 3.5 in the 2.5 mg tanezumab, 2.5/5 mg tanezumab, and placebo groups, respectively, and decreased to 2.4, 2.4, and 2.7, respectively.
“Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%),” the study authors further observed. “The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively.”
The study authors concluded, “Among patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and AE findings.”