Tanezumab Reduces Joint Pain, but Possibly at the Cost of Further Joint Damage

By Reuters Staff

July 05, 2019

NEW YORK (Reuters Health) - A new industry study provides more evidence that tanezumab is an effective analgesic for osteoarthritis, but it also confirms an increased risk of rapidly progressive OA and total joint replacement seen in earlier trials.

"While the mechanisms linking tanezumab to rapidly progressive OA and total joint replacement 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," writes Dr. Jeffrey Katz of Boston's Brigham and Women's Hospital in an editorial published with the study in JAMA today.

Tanezumab is an investigational humanized monoclonal antibody that binds and inhibits nerve growth factor (NGF). It's being developed by Pfizer and Eli Lilly and Company, which funded the current trial.

Dr. Thomas Schnitzer from Northwestern University Feinberg School of Medicine in Chicago and colleagues enrolled 696 patients with hip or knee OA; pain and function scores of 5 or greater on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); an inadequate response to OA analgesics; and no radiographic evidence of prespecified joint safety concerns.

Patients were randomly allocated to one of three subcutaneous-injection regimens: placebo at weeks 1 and 8; tanezumab 2.5 mg at weeks 1 and 8; or tanezumab 2.5 mg at week 1 and 5 mg at week 8. Intermittent acetaminophen was allowed if needed.

Tanezumab provided statistically significant improvements over placebo in WOMAC pain and physical function and patient global assessment of osteoarthritis (PGA-OA) at week 16, the investigators report.

For example, 54.7% of placebo-treated patients saw at least a 30% reduction in WOMAC pain between baseline and 16 weeks compared to 68% of patients in the 2.5-mg group (P=0.006) and 70.4% of those in the 2.5/5-mg group (P<0.001). The corresponding percentages for at least a 50% reduction in pain were 37.9%, 54.5% and 57.1%.

However, rapidly progressive OA occurred only in tanezumab-treated patients, with five cases (2.2%) in the 2.5-mg group and one (0.4%) in the 2.5/5-mg arm.

Tanezumab-treated patients also underwent more total joint replacements in the 40-week observation period, with eight (3.5%) such cases in the 2.5-mg group and 16 (6.9%) in the tanezumab 2.5/5.0-mg group versus four (1.7%) in the placebo group.

"These differences were statistically significant and suggest a dose-related increased frequency of total joint replacement in tanezumab-treated patients," Dr. Katz notes in his editorial.

He also points out that this study had several of the design features intended to reduce the incidence of rapidly progressive OA and joint replacement associated with tanezumab, including moderate dosing, no concomitant use of NSAIDs, and the exclusion of people with avascular necrosis or subchondral insufficiency fracture.

Dr. Katz says the question that emerges from the studies of tanezumab is whether its analgesic benefits merit the potential joint damage and risk of rapidly progressive OA and total joint replacement.

"If the medication is approved for clinical use in OA, patients and physicians will need to discuss these risks and benefits carefully," he writes. "Patients considering this therapy will need to accept the possibility that tanezumab has the potential to hasten symptomatic OA progression and consideration of total joint replacement. For those patients at high risk for total joint replacement-related complications and those with strong preferences to avoid total joint replacement at all costs, tanezumab would not be a wise choice. Patients willing to accept the risk of total joint replacement in exchange for a greater probability of pain reduction than afforded by other available therapies would appear to be acceptable candidates for tanezumab."

Dr. Schnitzer and colleagues agree that further research is needed to determine the "clinical importance of these efficacy and adverse event findings."

The study was sponsored by Pfizer and Eli Lilly and Co. Several authors have disclosed financial relationships with the companies.

SOURCE: http://bit.ly/2xojdm3 and http://bit.ly/2xnMM7n

JAMA 2019.

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