The TGA says romosozumab should only be prescribed if the benefits outweigh the risks.
Romosozumab is contraindicated in patients with a history of heart attack or stroke, the TGA has warned after investigating the risks of the osteoporosis drug.
The TGA said clinicians should discuss the balance of risks and benefits with patients who are taking romosozumab (Evenity, Amgen), which is listed on the PBS for severe, established osteoporosis in men and postmenopausal women.
Rheumatologist and head of rheumatology at Sydney’s Westmead Hospital, Associate Professor Peter Wong, said treatment decisions should be made on a case-by-case basis after weighing the risks and benefits for each patient.
“We’ve known that in someone with unstable cardiovascular disease, romosozumab is probably not the right drug to use,” said the medical director of Healthy Bones Australia.
“Have a chat to the patient about risks and benefits, and come to a shared decision as to whether the drug is appropriate. It’s always a matter of matching the right drug to the right patient.”
The TGA updated the medication’s Product Information and Consumer Medicine Information to include new warnings about the potential risks of major adverse cardiac events in patients after examining evidence from the ARCH trial, which showed an increase in myocardial infarction and stroke in patients treated with Evenity compared to controls.
“Evenity is contraindicated in patients with previous myocardial infarction or stroke,” the Product Information now says.
“When determining whether to use Evenity for an individual patient, consideration should be given to their fracture risk over the next year and their cardiovascular risk based on risk factors (e.g. established cardiovascular disease, hypertension, hyperlipidaemia, diabetes mellitus, smoking, severe renal impairment, age).
“Evenity should only be used if the prescriber and patient agree that the benefit outweighs the risk.”
The TGA said it had received nine case report notifications of serious adverse events, with two leading to death.
But the TGA added: “We consider that the benefit-risk balance of romosozumab remains positive, and it continues to be a useful treatment for osteoporosis for some patients.”
Professor Wong said a patient with severe osteoporosis had a 30% risk of dying in the 12 months after having a hip fracture.
“This is not a benign disease, and we’re talking about a very small increased risk in a major adverse cardiovascular event, probably heart attack or stroke.
“If you have a hip fracture, there’s a 30% mortality at 12 months, and we know that effective treatment for osteoporosis halves your risk of having a fracture.”
Professor Wong said if a patient had had a heart attack in the previous 12 months, or had unstable angina or a recent stroke, he probably would not use romosozumab because of the ARCH study results.
“But if someone had terrible osteoporosis, they were fracturing and I knew I could halve their risk by giving them romosozumab, and they’ve had a history of vascular disease, I would have to chat with them and say, ‘this is a really effective drug at thickening your bones, but it may increase the risk of heart attack and stroke. What do you think?’”
The TGA investigated the risks of romosozumab after conflicting evidence from two trials.
One 2016 study in the NEJM found no difference in major adverse cardiac events between the romosozumab and the placebo groups in postmenopausal women.
However, the 2017 ARCH study in the NEJM found that serious cardiovascular events were more frequent in among postmenopausal women who took romosozumab compared with those who took alendronate for 12 months.
The double-blind, phase III active-controlled ARCH study found that 50 patients (2.5%) in the romosozumab group and 38 (1.9%) in the alendronate group reported serious cardiovascular adverse events (OR 1.31, 95% CI 0.85 to 2.00).
The researchers noted that alendronate was associated with a reduced risk of CV disease in some studies.