EUROPEAN NON-INTERVENTIONAL POST AUTHORIZATION SAFETY STUDY RELATED TO SERIOUS INFECTIONS FOR ROMOSOZUMAB BY THE EU ADR ALLIANCE

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  EVENITY
• Study drug International non-proprietary name (INN) or common name:
  ROMOSOZUMAB

  ALENDRONIC ACID

  IBANDRONIC ACID

  RISEDRONATE SODIUM

  DENOSUMAB

  TERIPARATIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (M05BX06) romosozumab

  romosozumab

  (M05BA04) alendronic acid

  alendronic acid

  (M05BA06) ibandronic acid

  ibandronic acid

  (M05BA07) risedronic acid

  risedronic acid

  (M05BA08) zoledronic acid

  zoledronic acid

  (M05BA06) ibandronic acid

  ibandronic acid

  (M05BX04) denosumab

  denosumab

  (H05AA02) teriparatide

  teriparatide
• Medical condition to be studied:
  Osteoporosis postmenopausal

  Infection

Population studied

• Short description of the study population:
  The study population will comprise of all women from the 7 participating data sources with severe OP who are dispensed or prescribed an OP medication of interest for the first time (new user) during the study period, have been continuously registered in the data source for at least 12 months prior to the first recorded dispensing/prescription of the OP medication of interest, and are at least 50 years of age on the date of the first dispensing/prescription of the OP medication of interest. Women with a diagnosis of cancer (any except basal cell skin cancer) or Paget disease at any time before treatment initiation will be excluded.
• Age groups:
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  328256

Study design details

• Study design:
  This will be a multi-national, multi-database cohort study of new users of romosozumab and new users of other OP medications. The study period is expected to last for 4 years (2020 to 2024).
• Main study objective:
  The overarching objective of this study is to monitor the potential risk of serious infection (SI) associated with the use of romosozumab in comparison with other available osteoporosis (OP) medications in routine clinical practice in Europe.
• Setting:
  Participants from 7 European countries, including North, South and Central Europe, will be included. Data from primary care, secondary care, health registers, prescription/dispensation registers and claims will be utilized.
• Comparators:
  Alendronate (ATC M05BA04) will be the active comparator in the comparative safety analyses (Objective 3).
• Outcomes:
  Serious infection (SI) leading to hospitalization, Death due to Serious infection (SI), operationalized as either of:- In-hospital death with a diagnosis of infection during the same admission/episode- Recorded diagnosis of any infection followed by death in the subsequent month
• Data analysis plan:
  Incidence rates and 95 % confidence intervals (CIs) for Serious Infection (SI) events will be calculated for each study drug cohort using a Poisson model. These will be reported for prespecified intervals of 6, 12, 18, and 24 months after treatment indexes, and will be stratified by key SI risk factors. For comparative safety studies, propensity score matching will be used to match patients using romosozumab to up to 3 users of alendronate. Cox regression models stratified by matched sets will be used to calculate hazard ratios and 95 % CIs for each of the safety endpoints (SI leading to hospitalization and SI leading to death) according to drug exposure in the propensity-matched cohorts. The pooled estimates of the incidence rate for the databases will be calculated using the random or fixed effects meta-analysis depending on heterogeneity detected using an I^2 threshold of >40 %.