Denosumab safe, tolerable for long-term use in osteoporosis

Data from an analysis of the FREEDOM trial demonstrate that long-term use of denosumab did not result in increased common or low-frequency adverse events compared with a shorter duration of treatment.

“Denosumab (Prolia; Amgen Inc.) is a fully human monoclonal antibody against RANKL [receptor activator of nuclear factor kappa-B ligand] approved for the treatment of postmenopausal women with osteoporosis at increased or high risk of fracture,” Nelson B. Watts, MD, of Mercy Health, Cincinnati, Ohio, and colleagues wrote. “Osteoporosis is a chronic condition typically requiring long-term treatment. Recent data indicate relatively long life expectancies at the time patients initiate osteoporosis therapy, including more than 13 years on average for a 75-year-old woman.”

The FREEDOM trial, a phase 3, multicenter, randomized, double blind placebo-controlled study, took place over 3 years across 214 centers. Trial participants were women aged 60 to 90 years, and they received either placebo or 60-mg subcutaneous denosumab. All women from the initial trial were invited to participate in the extension trial, during which they continued denosumab treatment for an additional 7 years.

Three years after the extension study began, 3,547 participants (78%) remained in the study. Watts and colleagues reported that incidence rates for patients in the crossover group (1 to 3 years on denosumab) and the long-term group (4 to 6 years) were similar to those of both the placebo and denosumab groups from the FREEDOM trial for adverse events, such as hypercholesterolemia and cystitis, and lower than incidence rates of back pain, pain in extremity and musculoskeletal pain.

Patients in the extension showed bone mineral density gains and reductions in bone turnover markers that were similar to those of the initial trial.

“We found no evidence for a relationship between treatment with denosumab and increasing rates of either low frequency adverse events or common adverse events in patients who were assigned to placebo in the FREEDOM trial and received 3 years of denosumab in the extension study, and no indication of increased incidence of low frequency adverse events and common adverse events in patients receiving denosumab in years 4 to 6 compared with years 1 to 3,” the researchers wrote. “Our assessment is that this analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab.” – by Andy Polhamus

Disclosure: The study was funded by Amgen. Watts reports serving as a speaker or consultant for Abbvie, Amgen, Merck, Radius, Sanofi and Shire; receiving research grants from Shire; and holding stock or stock options with Osteodynamics. Please see the full study for a complete list of all other author’s relevant financial disclosures.