Romosozumab 105mg/1.17ml solution for injection pre-filled disposable devices

BackgruoundRomosozumab, a potent anabolic agent for osteoporosis, has been associated with an increased risk of adjudicated cardiovascular events compared with alendronate in postmenopausal women, although such an association was not observed in a placebo-controlled trial. Evidence from real-world clinical practice remains limited.MethodsIn this multicenter observational study, we analyzed patients aged ≥50 years who were newly prescribed romosozumab 120 mg monthly or denosumab 60 mg every 6 months for osteoporosis at three tertiary hospitals in South Korea between January 1, 2020, and the end of each site's data collection period. The primary outcomes were major adverse cardiovascular events (MACE; acute myocardial infarction, ischemic stroke, or sudden cardiac death) and all cardiovascular adverse events (CVAEs; MACE, heart failure, peripheral artery disease, and non-coronary revascularization), assessed at 1- and 3-year follow-up. Large-scale 1:1 propensity score matching and Cox proportional hazards models were applied within a common data model framework with individual-level meta-analysis.ResultsA total of 4,896 patients were included in the MACE analysis (4,758 in the CVAE analysis). At 1 year, the incidence rate of MACE did not differ significantly between the romosozumab and denosumab groups (9.20 per 1,000 person-years vs. 6.43 per 1,000 person-years; adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 0.64 to 3.19). The risk of CVAE was also similar between groups (16.23 per 1,000 person-years vs. 15.45 per 1,000 person-years; aHR, 1.05; 95% CI, 0.62 to 1.78). At 3 years, no significant differences were observed for MACE (aHR, 1.51; 95% CI, 0.79 to 2.88) or CVAE (aHR, 1.04; 95% CI, 0.69 to 1.58).ConclusionIn real-world clinical practice, romosozumab use was not associated with a statistically significant increase in cardiovascular risk compared with denosumab.

Abstract licence: CC BY-NC

BackgroundPostmenopausal osteoporosis is a highly prevalent disease associated with substantial morbidity and mortality. The most recently introduced osteoporosis medication is romosozumab, a monoclonal antibody with a unique mechanism of action that increases bone mineral density (BMD) more than other agents by both stimulating new bone formation and inhibiting resorption. The drug's stimulation of bone formation, however, wanes after several months. The use of romosozumab is limited by cost, the inconvenience of monthly clinic-administered injections, and its cardiovascular risk profile. In this trial, we aimed to test the hypothesis that a shorter course of romosozumab might be equally effective as the standard regimen.MethodsWe did a 12-month, prospective, open-label, randomised, controlled, non-inferiority trial of 50 postmenopausal women at high risk of fracture. The study was done at a single academic medical centre in the USA. Participants were randomly assigned to receive 3 months of romosozumab (210 mg by subcutaneous injection, monthly) followed by 9 months of denosumab (60 mg by subcutaneous injection, every 6 months; 3-month ROMO group) or 12 months of romosozumab (12-month ROMO group). The primary endpoint was the percentage change in total hip BMD. The non-inferiority threshold was set at 2%. The trial was registered at ClinicalTrials.gov, NCT05010590.FindingsBetween March 2, 2022, and May 2, 2023, we screened 188 participants. Of those, 102 (54%) were ineligible and 36 (19%) declined to participate. We randomly assigned 50 participants to either the 3-month ROMO group (24 [48%] participants) or the 12-month ROMO group (26 [52%] participants). Study participants completing at least one post-baseline visit were included in the analysis (modified intention-to-treat analysis). The mean age of participants was 69·6 years (SD 4·5). The mean 12-month change in total hip BMD was 5·7% (SD 3·3) in the 3-month romosozumab group and 6·0% (3·2) in the 12-month romosozumab group, meeting the prespecified non-inferiority threshold. Adverse events (back pain, cough, fatigue, headache, joint pain, muscle cramps, muscle pain, palpitations, paraesthesia, reaction at injection site, rhinorrhoea, skin rash, and swelling) were balanced between groups.InterpretationIn postmenopausal women at high risk of fracture, 3 months of romosozumab followed by 9 months of denosumab was non-inferior to 12 months of romosozumab in increasing total hip BMD. Given the expense, injection burden, and potential adverse effects of romosozumab, this abbreviated approach could broaden access to this uniquely effective therapy.FundingUS National Institute of Arthritis and Musculoskeletal and Skin Diseases and US National Center for Advancing Translational Science.

Abstract licence: CC BY-NC-ND