Hydroxychloroquine safety and potential efficacy as an antiviral prophylaxis in light of potential wide-spread use in COVID-19: a multinational, large-scale network
cohort and self-controlled case series study

Study type

• Study topic:
  Human medicinal product

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

  Effectiveness study (incl. comparative)

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

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Self-controlled case series

Study drug and medical condition

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

  SULFASALAZINE

  AZITHROMYCIN

  AMOXICILLIN
• Medical condition to be studied:
  Rheumatoid arthritis
• Additional medical condition(s):
  Coronavirus

Population studied

• Short description of the study population:
  Participants will be identified using pre-specified concept sets reviewed by a core team of clinicians, epidemiologists, vocabulary experts, and health data scientists with extensive expertise in the use of the OMOP CDM and the OHDSI tools.; New user exposure cohorts; Exposure cohorts will be defined where treatment initiation is the index event and includes the following criteria:; • History of RA: Have a condition occurrence or observation indicating RA any time before or on the same day as the index event; • Be aged 18 years or over at index event; • Have at least 365 days of continuous observation time prior to index event.; SCCS exposure cohorts; Additional exposure populations, regardless of indication, will be included for the SCCS. For each exposure population, all prevalent users of HCQ will be included and periods of inferred persistent exposure by allowing up to 90 day gaps between dispensing/prescription records will be constructed. Individual SCCS analyses will therefore be executed separately for each of the proposed study outcomes, including both safety events and negative control outcomes.
• 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:
  Immunocompromised
• Estimated number of subjects:
  800000

Study design details

• Main study objective:
  To study the safety of hydroxychloroquine and the combination of hydroxychloroquine + azithromycin in terms of severe adverse outcomes. Secondly, to study the association between the use of these medicines and the risk of viral infection/s and pneumonia.
• Data analysis plan:
  All analyses are conducted using an international distributed data network with shared analytical tools. For the comparative cohort analyses, propensity score stratification and calibration using negative control outcomes will be used to minimise observed and unobserved confounding respectively. Cox regression models were fitted to estimate Hazard Ratios according to drug exposure. Secondly, self-controlled case series analyses were used, where Incidence Rate Ratios for on vs off-treatment risk of each of the outcomes is estimated using a modified Poisson regression model, adjusted for age and seasonality.

Documents

Study publications

Lane JC, Weaver J, Kostka K, Duarte-Salles T, Abrahao MT, Alghoul H, Alser O, A…