Tanezumab reduces pain of hip or knee DJD and improves function, but may increase the need for joint replacement

Reference

Schnitzer TJ, Easton R, Pang S, et al. Effect of tanezumab on joint pain, physical function, and patient global assessment of osteoarthritis among patients with osteoarthritis of the hip or knee. A randomized clinical trial. JAMA 2019;322(1):37-48.

Synopsis

Tanezumab is a monoclonal antibody that inhibits nerve growth factor binding, which, when uninhibited, enhances pain hypersensitivity. These investigators identified adults, 18 years and older, who met standard international diagnostic criteria for hip or knee osteoarthritis. Eligible patients had a documented history of insufficient pain relief from acetaminophen and insufficient pain relief or intolerance/contraindication to nonsteroidal anti-inflammatory drugs, tramadol, and opioids. Additional eligibility criteria included a pain subscale score of at least 5 (on a scale where 0 = no pain and 10 = extreme pain) and a baseline physical function score of at least 5 (on a scale where 0 = no difficulty and 10 = extreme difficulty). Study participants randomly received (concealed allocation assignment) 1 of 2 subcutaneous tanezumab treatment regimens (2.5 mg at baseline and again at week 8, or 2.5 mg at baseline and 5.0 mg at week 8) or matched placebo. Individuals masked to treatment group assignment assessed all outcomes. Complete follow-up occurred for 98.8% of participants at 16 weeks. Using intention-to-treat analysis, pain scores were significantly reduced in both tanezumab groups compared with the placebo group (mean differences vs placebo of -0.60 for tanezumab 2.5 mg and -0.73 for tanezumab 2.5/5 mg). Similarly, physical function disability scores were significantly reduced in both tanezumab groups compared with the placebo group (mean differences vs placebo of -0.66 for tanezumab 2.5 mg and -0.89 for tanezumab 2.5/5 mg). Since these differences are all less than 10% (1 point or more on the 11-point scale), it remains uncertain whether these are clinically significant. The total amount of rescue medication (acetaminophen) used was not significantly different among the 3 treatment groups. Of concern: More patients from both the 2.5 mg group and the 2.5/5 mg group underwent total joint replacements than from the placebo group (3.5% and 6.9% vs 1.7%, respectively).