Post-authorization Safety Surveillance Program for Sarilumab using existing European Rheumatoid Arthritis Registries in Germany, Spain, Sweden and United Kingdom

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  SARILUMAB

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Pregnant women

  Renal impaired
• Estimated number of subjects:
  1925

Study design details

• Main study objective:
  To monitor, in real-world clinical practice, the long-term safety of sarilumab and evaluate the risk of selected outcomes of interest (including serious infections, malignancies, MACE, GI perforations) in patients with RA, this safety program will be conducted in four European countries.
• Outcomes:
  In real-world clinical practice in each study country:; 1. To monitor long-term safety of sarilumab by estimating incidence rates of outcomes of interest among patients treated with sarilumab, including serious infections, malignancies, GI perforations, and MACE ; 2. To estimate hazard ratios (HRs) of the outcomes of interest in the sarilumab cohort as compared to the bDMARDs/JAKis cohort, 1.Provide additional background information for the sarilumab and bDMARDs/JAKis cohorts by estimating incidence rates of the outcomes of interest in a cohort of patients exposed to conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs) in real-world clinical practice in each study country, except in Spain; 3. Conduct a meta-analysis to estimate the pooled HRs from the 4 registries
• Data analysis plan:
  Data analysis will be conducted separately for each registry. Demographic and baseline characteristics will be described in each cohort. Incidence rates of outcomes of interest will be estimated, including two-sided 95% confidence intervals (CIs), and Kaplan-Meier curves will be applied to characterize the time to onset of each outcome of interest in each cohort. Malignancies and MACEs will be studied using an ever-exposed approach while other OIs and MACEs will be studied using an on-treatment approach. Hazard ratios comparing sarilumab patients matched to bDMARDs/JAKis patients on the number of previous bDMARDs/JAKis and further adjust using propensity score method will be estimated. A meta-analysis of the 4 registries will be conducted to estimate the pooled HRs of the outcomes of interest, regardless of heterogeneity. The heterogeneity of the HRs across the registries will be examined by both Q statistic and I-squared index and investigations will be carried out in case of significant heterogeneity. Sensitivity analyses will be conducted to explore the impact of potential imbalance in key confounders. No comparison between the sarilumab cohort and the csDMARDs cohort will be done because of substantial differences in many factors between the two cohorts that would not be adequately controlled.