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In the ARCH trial, romosozumab plus alendronate outperformed alendronate alone in reducing fracture risk.
Treatment with romosozumab for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone in postmenopausal women with osteoporosis who were at high risk for fracture.
Romosozumab (Amgen and UCB Pharma), a new bone-forming monoclonal antibody, binds to and inhibits sclerostin, increasing bone formation and decreasing bone resorption. The antiresorptive agent alendronate is frequently used as first-line therapy for osteoporosis.
In the Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH), researchers at the University of Alabama, Birmingham and other centers compared the effectiveness of a treatment regimen starting with romosozumab and transitioning to alendronate with alendronate treatment alone in reducing the risk of fracture among 4093 postmenopausal women who had osteoporosis and a previous fracture.
They enrolled the women and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups.
The cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture at the time of the primary analysis were the primary end points. The incidences of nonvertebral and hip fracture at the time of the primary analysis were secondary end points.
Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated.
The researchers reported their findings in the New England Journal of Medicine.
Some key results:
• A 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group over 24 months.
• Clinical fractures occurred in 9.7% of patients in the romosozumab-to-alendronate group versus 13.0% of patients in the alendronate-to-alendronate group.
• The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (8.7% vs 10.6% of patients).
• The risk of hip fracture was lower by 38% in the romosozumab-to-alendronate group (2.0% vs 3.2% of patients).
• Overall adverse events and serious adverse events were balanced between the 2 groups.
• An imbalance in serious cardiovascular adverse events in comparison with alendronate was found that was not observed in a previous large, placebo-controlled trial.
The authors concluded that “rapid gains in bone mineral density from bone-forming therapy with romosozumab were associated with a lower risk of fracture than with alendronate within 1 year and over the course of romosozumab followed by alendronate.”
They suggested that the lower frequency of hip fractures with romosozumab followed by alendronate than with alendronate alone challenges the common practice of first-line use of alendronate in women who have had a previous fracture.
“By sharing the detailed results of efficacy and safety, we aim to help clinicians understand the future benefit:risk profile of romosozumab and its potential as a treatment option for postmenopausal women living with osteoporosis,” lead author Kenneth F. Saag, MD, MSc, professor of medicine at the UAB School of Medicine, said in a news release.
Funded by Amgen and others; ARCH ClinicalTrials.gov number, NCT01631214.
Saag KG, Petersen J, Brandi ML, et al. “Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis.” N Engl J Med. 2017 Sep 11. doi: 10.1056/NEJMoa1708322. [Epub ahead of print]