Tanezumab, an investigational monoclonal antibody that inhibits nerve growth factor, improved joint pain and physical function in patients with osteoarthritis, in a placebo-controlled clinical trial.
Although the agent demonstrated efficacy relative to placebo in study participants who had not obtained relief with conventional agents, the investigators characterized the improvement with tanezumab as modest, and found that it was associated with an increased incidence of rapidly progressive osteoarthritis (OA) and a requirement for total joint arthroplasty.
Such adverse effects would doom any other medication, but this one keeps getting promoted only because it’s not an opioid.
The trial had been designed to minimize these possible adverse events, lead author Thomas Schnitzer, MD, PhD, a professor of physical medicine and rehabilitation, anesthesiology, and medicine (rheumatology).
Dr. Schnitzer and his colleagues reported that rapidly progressive OA occurred only in tanezumab-treated participants, and that the incidence of total joint arthroplasty was significantly higher in that group than among those receiving placebo.
“While the mechanisms linking tanezumab to rapidly progressive OA have not been defined definitively, investigators hypothesize that these complications arise because with reductions in pain, patients bear increasing loads on damaged joints.
“In essence, then, the analgesic efficacy of tanezumab may be the reason for its most important toxicity,” Dr. Katz said.
This is just nonsense. If it were true, then it should be even more the case with opioids or any other pain reliever that’s effective for a patient “because, with reductions in pain, patients bear increasing loads on damaged joints”.
This is the worst kind of justification for damages, singling out a factor that’s common to all kinds of other cases, like pain relief, and blaming it for the damages of a new drug.
Testing the NGF Inhibitor
The investigation of NGF inhibition for the pain associated with OA follows from finding that the NGF neurotrophin is involved in pain signaling and nociceptor gene expression. Dr. Schnitzer and his colleagues pointed out that NGF also has been shown to contribute to the clinical symptom of pain hypersensitivity that often accompanies inflammation and chronic pain conditions.
Dr. Schnitzer and his colleagues identified 698 study participants who met the entry criteria.
The participants also had a documented history of insufficient pain relief from acetaminophen, as well as insufficient pain relief and intolerance/contraindication to NSAIDs, tramadol or opioids.
Participants were randomly assigned to either
- 2.5 mg subcutaneously at baseline and week 8,
- a titrated dose from 2.5 mg at baseline to 5 mg at week 8, or
- placebo injections. Participants were followed though week 24
The investigators reported that tanezumab demonstrated significantly greater improvements than placebo in pain, physical function and the PGA-OA at week 16. The titration to the 5-mg dose resulted in “nominally” greater improvements compared with those continuing on 2.5 mg, they noted.
Rapidly progressive OA occurred in patients receiving active treatment, but not in those on placebo.
The adverse event occurred in five (2.2%) of those on 2.5 mg, and in one (0.4%) of those on the 2.5-/5-mg regimen. The incidence of total joint arthroplasty was eight (3.5%), 16 (6.9%) and four (1.7%) in the tanezumab 2.5 mg, 2.5/5 mg and placebo groups, respectively.
I’ve had my doubts about this method of pain relief from the start. As is obvious from its name, “nerve growth factor” has other important functions in our bodies.
Just because it’s associated with pain doesn’t mean it should simply be “turned off” because we cannot know all the potentially damaging side effects from lowering its levels throughout our bodies.
This earlier post explains what other functions NGF performs in our bodies: Phase 3 Chronic Pain Program For Tanezumab.
Below are more posts about this class of medication: