AMSTERDAM – Greater increases in bone strength were achieved with denosumab (Prolia) than with risedronate in patients receiving glucocorticoid treatment in a phase 3 trial, suggesting it may prove to be an effective means of preventing osteoporosis in this at-risk population of patients.
At 2 years, the percentage change in bone mineral density (BMD) from baseline with denosumab compared to risedronate in patients initiating steroid treatment was significantly higher (all P values less than .001) at the lumbar spine (6% vs. 2%), total hip (3% vs. 0%), and the femoral neck (1.5% vs. –1%). Similar results were seen in patients who were continuing steroid treatment when they entered the randomized, multicenter, double blind trial.
These data build on the 1-year data that have just been published (), , the presenting study investigator, said at the European Congress of Rheumatology.
“Denosumab continued to increased BMD significantly more then risedronate through 24 months,” said Dr. Lems of VU University Medical Center, Amsterdam. He added that “the treatment differences at all skeletal sites were larger at 24 months than as 12 months.”
The Food and Drug Administration approved an additional indication in May of 2018 for denosumab to treat glucocorticoid-induced osteoporosis in adults at high risk of fracture. The biologic, a monoclonal antibody that targets the RANK ligand, was already approved to treat postmenopausal women with osteoporosis at high fracture risk, to increase bone mass in men with osteoporosis at high fracture risk, and to increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer and in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.
Secondary osteoporosis is a well known downside of glucocorticoid treatment, and despite there being approved therapies, many patients do not receive such treatment, Dr. Lems noted.
“Thisassessed the safety and efficacy of denosumab versus risedronate in glucocorticoid-treated individuals, in whom guidelines advocate treatment,” Dr. Lems said.
In all, 795 adults who were taking glucocorticoids (7.5 mg prednisone or more daily, or equivalent) were enrolled at 79 sites in Europe, North America, Latin America, and Asia. Patients were subdivided into two populations based on their duration of glucocorticoid use, with 290 designated “glucocorticoid initiating” as they had been treated for less than 3 months, and 505 as “glucocorticoid continuing” as they had been treated for 3 or more months. Within these groups, approximately half were randomized to receive denosumab at a 60-mg subcutaneous dose every 6 months and half to receive risedronate 5 mg orally every day. All participants received calcium and vitamin D supplementation.
Bone turnover markers also declined “significantly more” with denosumab than with risedronate, with the exception of procollagen type 1 N-terminal telopeptide on day 10 and at 2 years and serum C-telopeptide of type 1 collagen at 2 years.
As for safety, a similar percentage of adverse events, including serious adverse events, was seen, Dr. Lems said. So far, he added, “data seem to be reassuring” regarding the risk for serious infections in high-risk subgroups of patients, such as those also taking biologic or immunosuppressant medications. There were no infections reported in patients taking biologics (vs. 12.1% for risedronate) and fewer infections in those taking immunosuppressant or biologic medication (3.6% vs. 6.8%).
Although the study was not powered to look at the rate of fractures between the two treatments, Dr. Lems noted that there was no significant difference in the rates of either new vertebral (4.1% for denosumab; 5.8% risedronate) or clinical (5.8% vs. 6.3%) fractures at 2 years.
“Additional studies are needed to confirm if denosumab is superior to other bisphosphonates for BMD improvement and fracture reduction,” Dr. Lems said. “Denosumab may offer a useful osteoporosis treatment option for patients receiving glucocorticoids,” he concluded.
Amgen sponsored the study. Dr. Lems acknowledged ties to Amgen, Eli Lilly, and Merck: being on the speakers bureau, receiving honoraria for advisory board meetings, and acting as a consultant. All but one other author disclosed ties to Amgen.