title: GRAND-4: the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab.
abstract: This retrospective database study assessed 2-year persistence with bisphosphonates or denosumab in a large German cohort of women with a first-time prescription for osteoporosis treatment. Compared with intravenous or oral bisphosphonates, 2-year persistence was 1.5-2 times higher and risk of discontinuation was significantly lower (P < 0.0001) with denosumab.
  
  
  
  Persistence with osteoporosis therapies is critical for fracture risk reduction. Detailed data on long-term persistence (≥2 years) with bisphosphonates and denosumab are sparse.
  
  
  
  From the German IMS® database, we included women aged 40 years or older with a first-time prescription for bisphosphonates or denosumab between July 2010 and August 2014; patients were followed up until December 2014. The main outcome was treatment discontinuation, with a 60-day permissible gap between filled prescriptions. Two-year persistence was estimated using Kaplan-Meier survival curves, with treatment discontinuation as the failure event. Denosumab was compared with intravenous (i.v.) and oral bisphosphonates separately. Cox proportional hazard ratios (HRs) for the 2-year risk of discontinuation were calculated, with adjustment for age, physician specialty, health insurance status, and previous medication use.
  
  
  
  Two-year persistence with denosumab was significantly higher than with i.v. or oral bisphosphonates (39.8 % [n = 21,154] vs 20.9 % [i.v. ibandronate; n = 20,472] and 24.8 % [i.v. zoledronic acid; n = 3966] and 16.7-17.5 % [oral bisphosphonates; n = 114,401]; all P < 0.001). Patients receiving i.v. ibandronate, i.v. zoledronic acid, or oral bisphosphonates had a significantly increased risk of treatment discontinuation than did those receiving denosumab (HR = 1.65, 1.28, and 1.96-2.02, respectively; all P < 0.0001).
  
  
  
  Two-year persistence with denosumab was 1.5-2 times higher than with i.v. or oral bisphosphonates, and risk of discontinuation was significantly lower with denosumab than with bisphosphonates. A more detailed understanding of factors affecting medication-taking behavior may improve persistence and thereby reduce rates of fracture.
authors.affiliation: Department of Bone Oncology, Endocrinology, and Reproductive Medicine, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany. hadji.peyman@khnw.de.
authors.forename: P
authors.initials: P
authors.lastname: Hadji
authors.affiliation: Department of Bone Oncology, Gynecological Endocrinology and Reproductive Medicine, Nordwest Hospital, Frankfurt am Main, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Kyvernitakis
authors.affiliation: Centre for Internal Medicine - Endocrinology & Diabetes, Philipps University of Marburg, Marburg, Germany.
authors.forename: P H
authors.initials: PH
authors.lastname: Kann
authors.affiliation: Gemeinschaftspraxis, Heinsberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Niedhart
authors.affiliation: Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine 3 and Center for Healthy Aging, TU Dresden Medical Center, Dresden, Germany.
authors.forename: L C
authors.initials: LC
authors.lastname: Hofbauer
authors.affiliation: Facharztpraxis für Orthopädie und Physiotherapie, Freudenstadt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schwarz
authors.affiliation: Themistocles Gluck Hospital, Ratingen, Germany.
authors.forename: A A
authors.initials: AA
authors.lastname: Kurth
authors.affiliation: Department of Bone Oncology and Osteoporosis Center, Krankenhaus Nordwest, Frankfurt am Main, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Thomasius
authors.affiliation: Amgen (Europe) GmbH, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schulte
authors.affiliation: Amgen Europe, Zug, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Intorcia
authors.affiliation: Amgen Europe, Zug, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Psachoulia
authors.affiliation: Amgen (Europe) GmbH, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schmid
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006801:Humans; D055118:Medication Adherence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab
keywords: Bisphosphonates; Compliance; Denosumab; Osteoporosis; Persistence