Postauthorisation Safety Study (PASS) of Avatrombopag and Haematological Malignancies in Patients With Primary Immune Thrombocytopaenia

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  DOPTELET
• Anatomical Therapeutic Chemical (ATC) code:
  (B02BX08) avatrombopag

  avatrombopag
• Medical condition to be studied:
  Haematological malignancy

Population studied

• Short description of the study population:
  The study population will include adults with a new diagnosis of primary ITP recorded on at least 2 separate dates in 2006 or later. Two cohorts are defined: Avatrombopag Cohort and No Avatrombopag Cohort. For patients in the Avatrombopag Cohort, the date of the first dispensing/prescription of avatrombopag within the study period will be considered the index date (or day 0), contingent on meeting the other inclusion and exclusion criteria. Follow-up and outcome assessment will start on the day after the index date (day 1). Patients will be followed to the first of the following: occurrence of an outcome event, end of study period (initially planned for Q2 2027 in Sweden and Q1 2028 in Denmark), emigration, or death. For the No Avatrombopag Cohort, the date of the second diagnosis of primary ITP in the data source will be considered the index date (or day zero), and follow-up and outcome assessment will start on the day after the index date (day 1). Censoring events in the No Avatrombopag Cohort will be identical to those for the Avatrombopag Cohort except for the additional criterion that starting avatrombopag will end follow-up.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 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:
  The study population will consist of patients diagnosed with primary ITP, an acquired autoimmune disease
• Estimated number of subjects:
  200

Study design details

• Study design:
  Non-interventional, population-based, descriptive cohort study using routinely collected secondary data from the national health registers in Denmark and Sweden.
• Main study objective:
  The primary objective of the avatrombopag PASS is to estimate the IR of haematological malignancies among patients with primary ITP who initiate treatment with avatrombopag.
• Setting:
  Two cohorts are defined (details on eligibility criteria can be found in the protocol):; - Avatrombopag Cohort: Patients with a first ever dispensing/prescription of avatrombopag within the study period and who meet all the eligibility criteria before or on the index date (i.e., day 0 defined as the date of first dispensing/prescription of avatrombopag) will be assigned to the Avatrombopag Cohort. ; - No Avatrombopag Cohort: Patients who are newly diagnosed with primary ITP and who meet all eligibility criteria on the index date (i.e., day 0 defined as the date of the second diagnosis of primary ITP) will be assigned to the No Avatrombopag Cohort. ; For both cohorts, follow-up and outcome assessment start on the day after the index date (day 1) and censoring criteria are identical (i.e., occurrence of an outcome event, emigration, death, or end of the study period); the No Avatrombopag Cohort has an additional censoring criterion that includes initiation of avatrombopag.; The study period is 6 years starting on the date avatrombopag was approved for reimbursement in Denmark (28 January 2022) and Sweden (18 June 2021) and ending in Q1 2028 in Denmark and Q2 2027 in Sweden. The study period includes a 5-year enrolment period, allowing for a minimum of 1-year follow-up for all included patients (up to 6 years of follow-up).
• Comparators:
  To contextualize the primary analysis, the IR of haematological malignancies will also be estimated among patients newly diagnosed with ITP who have not received treatment with avatrombopag.
• Outcomes:
  Haematological malignancies will be defined during follow-up as the first record of any of their individual components:; - Myeloproliferative neoplasms; - Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of platelet-derived growth factor receptor alpha (PDGFRA), platelet-derived growth factor receptor beta (PDGFRB), or fibroblast growth factor receptor 1; - Myelodysplastic/myeloproliferative neoplasms; - Myelodysplastic syndrome; - Acute myeloid leukaemia and related precursor neoplasms; - Acute leukaemia of ambiguous lineage; - Precursor lymphoid malignancies; - Mature B-cell neoplasms; - Mature T-cell and natural killer (NK)–cell neoplasms; - Hodgkin lymphoma; - Histiocytic and dendritic cell neoplasms; - Post-transplant lymphoproliferative disorders
• Data analysis plan:
  Patient attrition in each of the study cohorts will be reported. The characteristics of patients in the two study cohorts according to the covariables defined at the index date and annually up to 5 years after ITP diagnosis will be described. The observed number of incident haematological malignancies in each cohort (Avatrombopag Cohort and No Avatrombopag Cohort) will be reported. Crude IR estimates of haematological malignancies overall and by age categories, sex, and time since ITP diagnosis will be estimated for each cohort with 95% CIs. The expected number of events in the Avatrombopag Cohort will be estimated based on the IRs in the No Avatrombopag Cohort using indirect standardisation stratified by age categories, sex, and time since ITP diagnosis. The standardised morbidity (incidence) ratio (SMR), the ratio of the observed to expected number of cases, will be reported with 95% CIs and will represent the IRR of haematological malignancies in the Avatrombopag Cohort compared with the No Avatrombopag Cohort.