medwireNews: Long-term treatment with tanezumab is associated with an increased risk for joint-related adverse events (AEs) in patients with hip or knee osteoarthritis (OA) and moderate-to-severe pain despite prior stable use of nonsteroidal anti-inflammatory drugs (NSAIDs), phase 3 study data show.
The findings, reported by Marc Hochberg (University of Maryland School of Medicine, Baltimore, USA) and co-authors in Arthritis & Rheumatology, are in line with those of a smaller, short-term trial previously reported by medwireNews.
For the current safety study, patients with WOMAC Pain and Physical Function scores of 5 or more, a fair, poor, or very poor patient’s global assessment of OA (PGA‐OA), a history of inadequate pain relief with standard analgesics, and no history of other bone or joint conditions were randomly assigned to receive subcutaneous tanezumab 2.5 mg (n=1002) or 5.0 mg (n=998) every 8 weeks or to twice‐daily oral naproxen, celecoxib, or diclofenac (n=996), each for 56 weeks followed by a 24-week post‐treatment follow‐up period.
The researchers report that, during the treatment period, the AE rates (including joint AEs) were similar among the three groups at 62.8%, 67.1%, and 60.3% for patients in the tanezumab 2.5 mg, tanezumab 5.0 mg, and NSAID groups, respectively, with serious AEs occurring in 5.1%, 8.0%, and 4.6%, respectively.
At 80 weeks, 125 patients met the criteria for the composite joint safety endpoint of rapidly progressive osteoarthritis type 1 (70.4% of events) or type 2 (14.4%), subchondral insufficiency fracture (13.6%), primary osteonecrosis (1.6%), or pathologic fracture (no cases). The most commonly affected joint was the knee (76.8%) followed by the hip (20.8%) and shoulder (2.4%).
After adjustment for observation time, Hochberg and team found that the composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and 5.0 mg than with NSAIDs, at rates of 38.3, 71.5, and 14.8 events per 1000 patient–years, respectively.
In terms of efficacy, patients who received tanezumab 5 mg had significantly greater improvements in WOMAC Pain and Physical Function scores at 16 weeks relative to those who received NSAIDs, with least-squares mean differences of 0.26 and 0.31, respectively, but there was no significant difference between the two groups in change in PGA-OA.
There was also no significant difference in pain, physical function, and PGA-OA improvements between the patients treated with tanezumab 2.5 mg and those given NSAIDs, and the proportion of patients with a 50% or greater improvement in WOMAC Pain scores was similar across all treatment groups.
Hochberg et al conclude that the results “raise several critical questions for future research, particularly the potential reasons for the imbalance in joint safety events and observed dose-response relationships, and how safety surveillance and risk mitigation can be further optimized for clinical practice.”
In spite of this, the authors suggest the monoclonal antibody “may have a role in the treatment of patients with hip or knee OA who have moderate-to-severe pain with inadequate pain relief from, intolerance to, or contraindications to standard treatments for OA pain, including NSAID.”
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