Safety Concerns Offset the Modest Improvements of Tanezumab in Osteoarthritis Save
JAMA reports that although tanezumab is modestly effective in moderate to severe osteoarthritis (knee or hip), with statistically significant improvements in pain and physical function, the tanezumab (TNZ) treated patients had more joint safety events and total joint replacements than patients treated with placebo.
Tanezumab is an investigational humanized monoclonal antibody that binds and inhibits nerve growth factor (NGF) and is being developed by Pfizer and Eli Lilly and Company.
In this trial a total of 698 hip or knee OA patients (refreactory to standard analgesic therapies) were randomized to receive placebo or 2 different dosing regimens of subcutaneous tanezumab given at 8-week intervals. The co–primary end points were the 16 week change in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10), WOMAC Physical Function (0-10) and patient global assessment of osteoarthritis (PGA-OA) (1-5) scores.
The mean age was 60.8 years; 65.1% women), and 84% completed the trial. The results from baseline to 16 weeks are shown below:
|Dose||TNZ 2.5mg||TNZ 2.5/7.5||PBO|
7.1 to 3.6 (P=0.01)*
|7.3 to 3.6 (P=0.002)*||7.3 to 4.4|
|WOMAC Function||7.2 to 3.7 (P=0.007)*||7.4 to 3.6 (P<0.001)*||7.4 to 4.5|
|PGA-OA||3.4 to 2.4 (P=0.01)*||3.5 to 2.4 (P=0.004)*||3.5 to 2.7|
*p Values compared to placebo
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 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.
Although statistically significant, the risk of rapidly advancing joint damage with this nerve growth factor inhibitor questions the practicality and utility of tanezumab for treatment of osteoarthritis.