7 May 2020

Tanezumab on trial again for OA

Clinical Osteoarthritis

Difficult-to-treat patients with advanced osteoarthritis (OA) receive modest pain relief with tanezumab over 24 weeks, a phase III study shows, but concerns remain for the rare, but serious, side effects that have halted studies in the past.

Tanezumab is a humanised monoclonal antibody that blocks nerve growth factor (NGF), which is involved in pain signalling and inflammation.

It showed great promise in early studies, providing potent pain relief. However, its progress was halted when some patients developed rapidly progressive OA (RPOA).

Trials have since resumed testing lower doses of tanezumab. There are also a number of trials testing other NGF inhibitors, but none have been approved to date.

This latest phase III study of tanezumab, sponsored by Pfizer, investigated its efficacy and safety in patients with moderate-to-severe OA of the knee and hip who had no relief from the usual analgesics.

People received three subcutaneous injections (either 2.5 or 5 mg tanezumab, or placebo) over 24 weeks, at which point their pain and physical function was assessed relative to baseline. A 24-week follow-up period ensued.

With almost 850 patients enrolled in the study, tanezumab did statistically improve pain and physical function. However, there were a few cases of RPOA reported at 48 weeks with patients on tanezumab, but none in the placebo group. Total joint replacements were similar across all three groups.

“Despite the statistical significance, the improvements in pain and function are modest,” said Dr Shirley Yu and Professor David Hunter, two rheumatologists from the Institute of Bone and Joint Research in Sydney. Yu said the results appeared less meaningful when considering the average differences in overall pain relief between the three groups.

Professor Flavia Cicuttini, the head of rheumatology at Alfred Hospital in Melbourne, said the clinical usefulness of this drug remains unclear and cautioned safety first, given its track record. “What you don’t want is to end up having more hip or knee replacements in a year when [this drug only] has a modest effect on pain,” she said.

Professor Cicuttini said the concern, like with previous studies, was that there seemed to be an acceleration of OA in some patients taking tanezumab compared to placebo, with marginally more joint replacements also reported after 48 weeks. The study also didn’t look at whether the pain relief persisted in follow-up, she said.

Professor Graeme Jones, a rheumatologist who leads the Musculoskeletal Research Group at the Menzies Institute for Medical Research in Hobart, agreed that the side effects were concerning but said new treatments for OA were sorely needed.

Jones said the drug could be offered to patients – but only those with severe disease – if activity guidelines were developed to mitigate the risk of progressive disease. The reported joint damage could be caused by patients suddenly increasing their activity after major pain relief, he said.

Citing his own previous study, Jones suggested patients taking this drug could be advised to reduce their exercise to prevent further damage (i.e. take fewer than 10,000 steps a day and avoid weight-bearing exercise).

“The next question is to look at measures of physical activity in patients taking tanezumab, to see if that activity correlates with who gets rapidly progressive damage,” he said.

Ann Rheum Dis 2020, March 31