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John Francis Acquavella

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

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  • John Acquavella
  • Vera Ehrenstein
  • Morten Schiødt, Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen, Denmark.
  • ,
  • Uffe Heide-Jørgensen
  • Anders Kjellman, Department of Urology, Karolinska University Hospital; Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
  • ,
  • Svein Hansen, Department of Paediatrics, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Norwegian Cancer Registry, Oslo, Norway.
  • ,
  • Cecilia Larsson Wexell, University of Gothenburg
  • ,
  • Bente Brokstad Herlofson, Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.
  • ,
  • Sven Erik Noerholt
  • Haijun Ma, Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA.
  • ,
  • Katarina Öhrling, Clinical Development, Amgen Inc., Thousand Oaks, CA, USA.
  • ,
  • Rohini K Hernandez, Center for Observational Research, Amgen Inc., One Amgen Center Drive, MS 24-2-A, Thousand Oaks, CA 91320, USA. Electronic address: karynsah@amgen.com.
  • ,
  • Henrik Toft Sørensen

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies.

METHODS: As part of a comprehensive pharmacovigilance plan, developed with regulators' input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly established national ONJ databases and adjudicated by the committee that functioned during the XGEVA(®) clinical trials program.

CONCLUSION: This study will provide a real world counterpart to the clinical trial-estimated risks for ONJ and serious infections for cancer patients initiating denosumab or zoledronic acid. The establishment of ONJ databases in the three Scandinavian countries will have potential benefits outside this study for the elucidation of ONJ risk factors and the evaluation of ONJ treatment strategies.

Original languageEnglish
JournalClinical epidemiology
Pages (from-to)267-72
Number of pages6
Publication statusPublished - 2016

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  • Journal Article

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