Proposal for establishment of a UK post-marketing surveillance registry to study the effectiveness, safety and prescribing habits of tocilizumab for the treatment of giant cell arteritis in the UK National Health Service, nested within the existing structure of the UK GCA Consortium and UKIVAS studies (TARGET)

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

  Effectiveness study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Name of medicine, other:
  Actemra
• Medical condition to be studied:
  Giant cell arteritis

Population studied

• Short description of the study population:
  Patients with refractory and relapsing GCA who fulfil NHSE criteria for tocilizumab prescription as part of their routine clinical care ; Patients already recruited to UK GCA who are prescribed tocilizumab from March 2019 will be invited to participate in the Registry sub-study and contribute longitudinal data at their clinical care visits.; Patients not already recruited to UK GCA will be invited to consent to the main UK GCA Consortium study and commence the longitudinal part of the study (the Registry sub-study) simultaneously. These would also be eligible for UKIVAS, and would be invited to separately consent to participate in the UKIVAS registry.
• Age groups:
  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with Temporal arteritis
• Estimated number of subjects:
  1000

Study design details

• Main study objective:
  Main objective is to assess the effectiveness and safety of tocilizumab in controlling refractory or relapsing GCA in patients who require escalation of therapy to reach sustained remission defined by the absence of active disease features.
• Outcomes:
  Proportion of patients treated with tocilizumab to control refractory or relapsing GCA in patients, who require escalation of therapy, to reach sustained remission (absence of active disease features and sustained reduction of glucocorticoid therapy to a maximum daily dose of 15mg prednisolone or equivalent within 3 months, and <5mg prednisolone or equivalent per day within 6 months). Safety and effectiveness of tocilizumab, characteristics of real-world patients compared to clinical trial populations, relapse rates, disease activity, ischaemic complications and drug related toxicity over the first year of treatment, patterns of glucocorticoid dosing, reasons for discontinuation of tocilizumab, prevalence of glucocorticoid toxicity, health-related quality of life (HR-QoL).
• Data analysis plan:
  Statistical analysis will be conducted in line with the study objectives according to a pre-specified Data Analysis Plan to be agreed. In particular, we will track cumulative steroid prescription and document post-tocilizumab flares and relapse. Data from controls will allow us to compare rates of relapse and toxicity, and glucocorticoid discontinuation between the two groups using appropriate multivariate survival models in order to explore the potential steroid-sparing effects of tocilizumab.