Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Romosozumab (Romo) is an investigational bone-forming monoclonal antibody that binds sclerostin and has a dual effect, increasing bone formation and decreasing bone resorption. Here, we report results of the FRActure study in postmenopausal woMen with ostEoporosis (FRAME) (NCT01575834).
Methods: This multicenter, randomized, double-blind, placebo-controlled study enrolled postmenopausal women aged 55 to 90 years with osteoporosis (BMD T-score ≤ –2.5 at the total hip or femoral neck). Subjects were randomized 1:1 to subcutaneous placebo (Pbo) or 210 mg Romo monthly for 12 months, followed by subcutaneous denosumab (DMAb) every 6 months for 12 months in both groups. The co-primary endpoints were subject incidence of new vertebral fracture through month (M) 12 and M24. Secondary endpoints included clinical (nonvertebral plus symptomatic vertebral) and nonvertebral fracture, and BMD.
Results: A total of 7180 women (mean age 71 years, mean total hip T-score –2.5) were enrolled. At M12, Romo reduced new vertebral fracture, with a relative risk reduction (RRR) of 73% (subject incidence of fracture: 1.8% Pbo vs 0.5% Romo; P < 0.001). In subjects who received Romo in year 1, vertebral fracture risk reduction persisted through M24 after both groups transitioned to DMAb (2.5% Pbo/DMAb vs 0.6% Romo/DMAb; RRR 75%; P < 0.001). Romo reduced clinical fracture risk at M12 (2.5% Pbo vs 1.6% Romo; RRR 36%; P = 0.008). Nonvertebral fracture incidence through M12 was 2.1% for Pbo (lower than expected) vs 1.6% for Romo (RRR 25%; P = 0.096), with a similar risk reduction through M24 (Pbo/DMAb vs Romo/DMAb RRR 25%; nominal P = 0.029, adjusted P = 0.057). A preplanned analysis revealed a significant interaction between treatment and geographic region for nonvertebral fracture at M12 (P = 0.042). Nonvertebral fracture incidence in Central/Latin America was 1.2% for Pbo vs 1.5% for Romo, whereas a 42% RRR in nonvertebral fracture was observed in rest-of-world (P = 0.012). Compared to Pbo, Romo increased BMD by 12.7% and 5.8% at the lumbar spine and total hip, respectively, at M12 (P < 0.001). Adverse events were generally balanced between groups, with injection-site reactions in 2.9% of Pbo subjects and 5.2% of Romo subjects during year 1. One atypical femoral fracture and 2 osteonecrosis of the jaw events were positively adjudicated in the Romo group through M24.
To cite this abstract in AMA style:Cosman F, Crittenden D, Adachi J, Binkley N, Czerwinski E, Ferrari S, Hofbauer L, Lau E, Lewiecki E, Miyauchi A, Zerbini C, Milmont C, Chen L, Maddox J, Meisner P, Libanati C, Grauer A. Fracture Risk Reduction with Romosozumab: Results of a Phase 3 Study in Postmenopausal Women with Osteoporosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/fracture-risk-reduction-with-romosozumab-results-of-a-phase-3-study-in-postmenopausal-women-with-osteoporosis/. Accessed December 5, 2020.
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