Romosozumab demonstrates superior efficacy to denosumab in GIO patients with high fracture risk: The interim results of a local pilot RCT

24 Jul 2023

Romosozumab is a humanized monoclonal antibody with the capability of decreasing bone resorption as well as promoting bone formation.1 It serves as a viable therapy for postmenopausal women with osteoporosis and high risk of fracture, as well as those who showed intolerance to other available therapies.1 However, the efficacy and safety of romosozumab in glucocorticoid-induced osteoporosis (GIO) remains inconclusive.1 In the EULAR 2023 , Dr. Mok, Chi-Chiu from Tuen Mun Hospital, Hong Kong, presented the interim results of a pilot randomized controlled trial (RCT), which compared the safety and efficacy of romosozumab and denosumab in GIO patients.1

This pilot study was a 24-month, open-label, randomized trial, which enrolled a total of 70 adult patients who had received daily treatment of prednisolone ≥5mg for ≥12 months and exhibited a moderate-to-high risk of osteoporotic fracture.1 There patients were randomized 1:1 to either receive 12 doses of monthly romosozumab 210mg subcutaneous injection (SQ) or 2 doses of 6-monthly denosumab 60mg SQ.1 All study participants were given daily supplements of calcium (caltrate 3,000mg/day) and vitamin D3 (cholecalciferol 1,000IU/day), with the romosozumab cohort switching to 6-monthly denosumab 60mg SQ injection from month 12 through month 24.1 The change in bone mineral density (BMD) in lumbar spine at month 12 served as the primary endpoint of this study.1 The secondary endpoints included BMD change in lumbar spine at month 24, BMD changes in hip and femoral neck at month 12 and month 24, changes in trabecular bone score (TBS) and hip geometry, bone turnover rate, incidence of adverse events (AEs), and incidence of vertebral and other major fractures.1

The interim results at month 12 showed a significantly greater BMD improvement in the lumbar spine in the romosozumab cohort compared with the denosumab cohort (7.3% vs. 2.3%; p<0.001).1 As for the change in hip BMD, both groups showed significant increase at month 12 but without significant between-group difference.1 Both groups did not show significant increase in the femoral neck BMD.1 In addition, significant drop in procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) was observed in the denosumab cohort at month 12 (P1NP: -35%; CTX: -35%), while the romosozumab cohort witnessed a numerical increase in the bone formation marker (+1.7%).1

Dr. Mok noted that due to its more frequent administration schedule, the romosozumab cohort experienced more injection-related AEs than its denosumab counterpart (28% vs. 14%).1 There were no serious AEs reported in both cohorts, and only 1 patient from the romosozumab arm developed vertebral fracture at month 12.1

In conclusion, the 12-month interim results of the pilot RCT demonstrated romosozumab’s superior efficacy in promoting lumbar spine BMD in high-risk GIO patients.1 Despite the more frequent injection-related AEs, romosozumab was generally well tolerated by patients.1 The results suggested that romosozumab may offer a new treatment option for GIO patients with high fracture risk.1

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