Real-World Comparability of Antiresorptive Osteoporosis Treatment Groups Among Treatment-Naïve and Treatment-Experienced Women Ages 55 and Older in the United States

Kathleen E Hurwitz,1 Lydia Feinstein,1 David A Pritchard,1 Peter Samai,1 Ying Yu,1 Min Kim,2 Akhila Balasubramanian,2 Tzu-Chieh Lin,2 Brian D Bradbury,2 M Alan Brookhart3 1Epidemiology, Target RWE, Durham, NC, USA; 2Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA; 3Department of Population Health Sciences, Duke University, Durham, NC, USACorrespondence: Kathleen E Hurwitz, Epidemiology, Target RWE, Road Ste 120, Box 377, Durham, NC, 27713, USA, Email KHurwitz@targetrwe.comPurpose: Selection of osteoporosis (OP) treatment is affected by patients’ disease severity and fracture risk, potentially confounding real-world comparative effectiveness and safety studies of antiresorptive medications. To inform the choice of valid treatment contrasts for subsequent real-world comparative studies, we assessed comparability of antiresorptive OP treatment groups using negative control outcomes (NCOs).Patients and Methods: Women aged ≥ 55 years in Optum© Clinformatics® Data Mart from October 2010 through June 2019 who received denosumab, zoledronic acid (ZA), or oral bisphosphonates (BPs) were included. We estimated the 1-year cumulative risks for 12 NCOs by treatment group among treatment-naïve and treatment-experienced women using augmented inverse-probability of treatment and censoring weighted (AIPW) estimation. A Bayesian sensitivity analysis was conducted to aggregate estimates and associated variances into a form characterized by magnitude and probability.Results: Women in both treatment-naïve (n = 199,335) and treatment-experienced (n = 33,296) cohorts initiated treatment at a mean age of 71.8 years. Treatment-naïve women initiating denosumab had similar 1-year risks of most NCOs compared with initiators of ZA (maximum observed RD = 2.47% for colon cancer screening). However, significant risk differences were observed for seven NCOs when comparing ZA or denosumab with oral BPs. Among treatment-experienced women, all NCOs indicated similar risks when comparing denosumab to alendronate ...