Effectiveness and Safety of Avacopan as Add-on to Standard of Care (SOC) Versus SOC Alone in ANCA-associated Vasculitis (LIBRA) (20240051)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  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:
  TAVNEOS
• Medicinal product name, other:
  Avacopan
• Study drug International non-proprietary name (INN) or common name:
  AVACOPAN
• Anatomical Therapeutic Chemical (ATC) code:
  (L04) IMMUNOSUPPRESSANTS

  IMMUNOSUPPRESSANTS
• Medical condition to be studied:
  Granulomatosis with polyangiitis

  Microscopic polyangiitis

Population studied

• Short description of the study population:
  Adults with newly diagnosed or relapsing GPA/MPA.
• Age groups:
  • Adult and elderly population (≥18 years)
• Estimated number of subjects:
  6000

Study design details

• Study design:
  This is a retrospective observational comparative effectiveness cohort study of avacopan + SOC vs SOC with sequential nested trials. Analyses will be performed separately by database. Results may be meta-analyzed pending assessment of cross-database overlap.
• Main study objective:
  The main objective of this study is to estimate the real-world effectiveness of avacopan + SOC versus SOC among adults with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
• Setting:
  This study will be conducted in multiple real-world data sources, including the Optum Market Clarity database and the Komodo Healthcare Map. Only closed claims will be used for this study. The study period will be from October 1, 2015, to the latest available date. The indexing period will be October 1, 2021, to 3 months prior to the latest available date.
• Comparators:
  Patients starting treatment for new/relapsing GPA/MPA with rituximab (RTX) or cyclophosphamide (CYC).
• Outcomes:
  The primary outcomes of this study are: ; 1. Time to first relapse.; 2. Number of Major Adverse Kidney Events (MAKE) within 12 months (composite endpoint of mortality, dialysis, kidney transplant, end-stage kidney disease).; 3. 30-day average prednisone-equivalent daily dose (PEDD) ≤ 7.5mg at 90, 120, 180, 270, and 365 days post- index.; ; The secondary outcomes of this study are: ; 1. Incidence of GC-related events within 12 months (composite of serious infection requiring hospitalization, initiation of new class of anti-hyperglycemic medication, major osteoporotic fractures [vertebra, pelvis, humerus, radius/ulna, hip, other femur]).; 2. Incidence of relapse within 12 months.; 3. Incidence of MAKE components within 12 months:; a. Mortality; b. Dialysis; c. Kidney transplant; d. End-stage kidney disease; 4. Incidence within 12 months of hepatotoxicity and drug-induced liver injury, and serious hypersensitivity reactions, including angioedema and anaphylaxis.; ; Post-hoc Analyses; ; • 30-day average PEDD (and change from baseline 30-day average PEDD) by 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360 days; • Cumulative glucocorticoid exposure by 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360 days; ; The post-hoc glucocorticoid exposure analyses described below were motivated by findings from the Optum Market Clarity analysis, which indicated that additional characterization of glucocorticoid use over time would be useful for interpretation of the comparative effectiveness results. These analyses were added after review of Optum results but before creation of the Komodo cohort and before conduct of the corresponding analyses in Komodo. Accordingly, these analyses are post-hoc for Optum and prespecified for Komodo.
• Data analysis plan:
  Analyses will be conducted separately within Optum Market Clarity and Komodo Healthcare Map using the same prespecified analytic framework. Within each database, analyses will proceed in stages with prespecified checkpoints to (a) confirm comparability of treatment groups after weighting, and (b) review of results from negative control outcome analyses. Descriptive analyses will summarize baseline characteristics overall and by treatment group, including disease severity proxies and treatment patterns. Meta-analysis may be conducted only if sufficient independent observations remain following assessment of cross-database overlap.