A novel analgesic for osteoarthritis may offer better pain relief than current options but at the risk of more progressive disease and higher rates of total joint replacement.

Tanezumab, a monoclonal antibody blocking nerve growth factor,  improved pain and physical function when compared to placebo in a trial of patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics.

But the 16-week randomised controlled trial involving 696 patients failed to dispel concerns from previous studies that tanezumab use was associated with high rates of joint damage and total joint replacements.

The analgesic efficacy of tanezumab may paradoxically lead to more joint damage and disease progression because the reductions in pain encourage patients to bear increasing loads on already damaged joints, a commentary accompanying the study in JAMA suggested.

Tanezumab was trialled in patients with pain and function scores of 5 or greater on the 11-point WOMAC scale, and with presence of osteophytes on radiographs. Patients received tanezumab 2.5mg by subcutaneous injection at week one and 2.5mg or 5mg at week eight, with paracetamol allowed as rescue medication.

Since tanezumab has previously been associated with rapidly progressive disease, the trial was designed to exclude patients with factors associated with this, such as those taking NSAIDs, and those with precursor lesions including subchondral insufficiency fractures or avascular necrosis.

Patients treated with tanezumab had significant reductions in pain compared to placebo (54.5% vs 37.9% had >50% reduction in WOMAC scores).

However, 6.9% of the high dose tanezumab-treated patients (2.5mg /5mg) and 3.5% of the 2.5mg/2.5mg treated patients had total joint replacements in the 40-week observation period: compared to 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, the commentary authors stated.

Nevertheless, some patients with more severe OA may be prepared to accept the possibility of tanezumab hastening  disease progression and  total joint replacement if the treatment provided relief from a high burden of pain and reduced function, the authors suggested.

“It could be argued that the risks of rapidly progressive OA and total joint replacement are too high for policy makers to permit entry of tanezumab into the market for advanced, symptomatic OA. However, given the prevalence and disability burden of OA, and the paucity of effective alternatives, it would be reasonable to allow patients and physicians to make these decisions together,” they wrote

Tanezumab would not be a wise choice for patients at high risk for total joint replacement–related complications and those with strong preferences to avoid total joint replacement at all costs, they added.

But it could potentially be made available to patients with a Risk Evaluation and Mitigation Strategy that imposes specific requirements to ensure that prescribers and patients are well informed about the short- and long-term benefits and potential harms of tanezumab, they concluded