medwireNews: Findings from a phase III trial conducted in the USA suggest that tanezumab improves pain and physical function scores relative to placebo among patients with moderate-to-severe hip or knee osteoarthritis (OA) and an inadequate response to analgesics.
However, Thomas Schnitzer (Northwestern University, Chicago, Illinois) and co-investigators say that “improvements were modest,” and people treated with tanezumab experienced more joint safety events and total joint replacements than those given placebo.
As reported in JAMA, the 231 patients who were randomly assigned to receive two doses of tanezumab 2.5 mg at an 8-week interval (fixed dose group) and the 233 given tanezumab 2.5 mg followed by a 5 mg dose 8 weeks later (dose titration group) experienced significantly greater improvements in the coprimary endpoints of WOMAC pain, WOMAC physical function, and patient global assessment for OA (PGA-OA) scores from baseline to week 16 than the 232 participants given placebo.
WOMAC pain scores decreased by a least squares (LS) mean of 3.23 points in the tanezumab fixed dose group and 3.37 points in the dose titration group, compared with a 2.64-point decrease for those given placebo. These findings translated into LS mean differences of 0.60 and 0.73 points for the fixed dose and titration groups, respectively, versus placebo.
Similarly, WOMAC function scores decreased by an average of 3.22 and 3.45 points in the fixed dose and dose titration groups, respectively, versus 2.56 points in the placebo group (LS mean difference versus placebo=0.66 and 0.89, respectively). The corresponding reductions in PGA-OA scores were 0.87 and 0.90 versus 0.65 points (LS mean difference=0.22 and 0.25, respectively).
Despite these benefits, participants in the tanezumab groups underwent “[s]ubstantially more” total joint replacement procedures over a 24-week follow-up period than those given placebo, say Schnitzer et al. Specifically, 3.5% of patients in the fixed dose group and 6.9% of patients in the dose titration group underwent at least one joint replacement, compared with just 1.7% of participants in the placebo group.
Moreover, adjudicated rapidly progressive OA occurred only in patients assigned to one of the tanezumab arms, at rates of 2.2% for the fixed dose group and 0.4% for the dose titration group.
“Further research is needed to determine the clinical importance of these efficacy and adverse event findings with regard to use of tanezumab for treatment of osteoarthritis,” say the investigators.
Writing in an accompanying editorial, Jeffrey Katz (Brigham and Women’s Hospital, Boston, Massachusetts, USA) notes that previous research has also demonstrated that tanezumab “is an effective analgesic for OA but is associated with higher frequency of rapidly progressive OA and total joint replacement.”
He says: “The question that emerges from these studies is whether the analgesic benefits of tanezumab merit the potential damage to the joint and attendant risk of rapidly progressive OA and total joint replacement.”
And Katz concludes that if tanezumab is approved for OA, “patients and physicians will need to discuss these risks and benefits carefully.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
JAMA 2019; 322: 37–48
JAMA 2019; 322: 30-32