Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study

Abstract

Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia. Introduction Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients. Methods In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences. Results This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups. Conclusions Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients.

Osteoporosis Treatment with Anti-Sclerostin Antibodies—Mechanisms of Action and Clinical Application

“…These findings imply that fracture risk assessment should consider regional factors in addition to the classical risk factors of BMD and fracture history. Accordingly, a sub-analysis of Japanese women in FRAME confirmed a similar efficacy of the romosozumab-to-denosumab regimen in these women compared to the overall FRAME population [ 79 ], while a sub-analysis of the East Asian cohort of ARCH showed that romosozumab followed by alendronate was associated with lower incidence of all fracture types studied (new vertebral, clinical, non-vertebral) vs. alendronate alone among East Asian patients [ 80 ].…”

“…In comparison to teriparatide, odds ratio for any adverse event was increased with romosozumab treatment [ 99 ]. A recent report described serious cardiovascular adverse events with romosozumab use in Japanese patients [ 103 ], although a sub-analysis from ARCH for East-Asian patients did not report an increased risk profile [ 80 ], and neither did the sub-analysis for Japanese patients from FRAME and its extension [ 79 ]. Mariscal et al performed a meta-analysis in men and women treated with romosozumab and described that adverse effects of romosozumab were comparable to placebo, except for an increased risk of adverse reactions at the injection site [ 104 ].…”

Effects of romosozumab or denosumab treatment on the bone mineral density and disease activity for 6 months in patients with rheumatoid arthritis with severe osteoporosis: An open-label, randomized, pilot study

“…Denosumab is a fully human monoclonal antibody that specifically and avidly binds to human RANKL, leading to diminished survival and activation of osteoclasts for bone resorption inhibition [ 8 , 9 ]. Romosozumab and denosumab are currently used in the treatment of postmenopausal osteoporosis [ 7 , [10] , [11] , [12] , [13] ]. Romosozumab treatment significantly increased bone volumes of vertebral body, knee, and ankle in mice model of RA compared with the control mice [ 14 ].…”

‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone-Tumor Mimetic Microenvironment

“…Romosozumab is a drug that was recently approved by the FDA for treatment of osteoporosis and functions by inhibiting expression of sclerostin, a glycoprotein and potent inhibitor of bone deposition [ 16 , 17 ]. However, a global phase III active-controlled fracture study in postmenopausal women with osteoporosis at high risk (ARCH) study revealed Romosozumab caused a 31% increase in major adverse cardiovascular events in patients taking the drug when compared to alendronate, the current standard of care [ 18 ]. Furthermore, teriparatide (sold under the brand name Forteo ® ) is a synthetic form of human parathyroid hormone that acts to promote bone density.…”