DARWIN EU® - Characterisation of exposure to acitretin and purpura and related conditions

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  ACITRETIN
• Anatomical Therapeutic Chemical (ATC) code:
  (D05BB02) acitretin

  acitretin
• Medical condition to be studied:
  Purpura

Population studied

• Short description of the study population:
  Patient-level characterisations (Objectives 1-2): New users of acitretin in the study period between 01/01/2010 and 31/12/2023 (or the latest date of data availability of the respective databases), with at least 365 days of visibility prior to the date of their first prescription and no prior use of acitretin. ; Population-level descriptive epidemiology (Objective 3): New users of acitretin, alternative treatments, and/or diagnosis of a condition of interest in the study period between 01/01/2010 and 31/12/2023 (or the latest date of data availability of the respective databases), with at least 365 days of visibility prior to the date of their first prescription and no prior use of the respective drug/s, will comprise the denominator population based on the respective treatment and indication groups.

Study design details

• Study design:
  • New drug user cohort (Objectives 1-2); • Population-level descriptive epidemiology (Objective 3)
• Main study objective:
  1. To characterise patients initiating treatment of acitretin in terms of:; a. Demographics; b. Treatment indications ; c. Risk factors for purpura and related conditions ; d. Comorbidities; ; 2. To describe patient-level acitretin utilisation in a cohort of new users including: ; a. Duration of treatment; b. Concomitant medications prescribed at/before/after index date ; ; 3. To estimate crude and age-sex standardised incidence rates of purpura and related conditions (and stratified by thrombocytopenic purpura vs non-thrombocytopenic purpura) in patients with common indications for acitretin and/or treatment groups, namely:; a. Treatment: methotrexate, cyclosporine, azathioprine-containing immunosuppressants; acitretin; TNF alpha inhibitors; interleukin inhibitors ; b. Indication (psoriasis vs other); c. Treatment-indication combination: Acitretin-psoriasis, Acitretin-keratinization, Acitretin-unknown/other, Methotrexate-psoriasis, Azathioprine/cyclosporine immunosuppressants-psoriasis, TNF alpha inhibitors-psoriasis, Interleukin inhibitors-psoriasis
• Outcomes:
  Outcomes of interest for the new-user cohort study were purpura and related conditions.
• Data analysis plan:
  Statistical analysis ; Analytical methods: ; Patient level characterisation was conducted any time before or on index date (date of first prescription of acitretin), including patient demographics, treatment indications, comorbidities pre-specified as known risk factors for purpura and related conditions. For drug utilisation, duration of treatment and concomitant medications at index date, 90 days before and 90 days after index date was reported. ; Incidence rates (IRs) were calculated for purpura and related conditions in acitretin users, those of other major treatment groups and those indicated for treatment with acitretin. Incidence rates per 100,000 person years were estimated crude and age-sex standardised using the European Standard Population. Results were reported for overall purpura and related conditions, and for thrombocytopenic purpura vs non-thrombocytopenic purpura. ; For all analyses a minimum cell counts of 5 was used when reporting results, with any smaller counts noted ; as <5.
• Summary results:
  Broadly, our study aimed to characterise acitretin use and purpura and related conditions across four routinely collected healthcare databases in the UK, Netherlands, Spain, and Denmark. New users of acitretin were generally in their mid-50s to 60s and with a higher proportion of males compared to females. Psoriasis was the most common indication, and the most common risk factor of acitretin new use was infectious disease. Across the four databases, the median number of acitretin prescriptions ranged between 1 and 2, and treatment duration ranged from 30 to 159 days. Most frequent comedications were systemic antibacterials, antidepressants and anti-inflammatory/anti-rheumatic drugs. ; Due to low number of events of purpura and related conditions overall in IPCI, IRs were not calculated for this database. Among the other three databases, age-sex standardised IRs for purpura and related conditions showed that events were uncommon (<1/100 to > 1/1000) to very rare (<1/10 000). Non-thrombocytopenic purpura showed consistently higher standardised rates than thrombocytopenic purpura. ; The psoriasis treatment group had the highest number of events. In this treatment group, the outcome of overall purpura and related conditions were uncommon in CPRD GOLD and rare (<1/1000 to ≥ 1/10 000) in SIDIAP and DK-DHR. Moreover, the outcome of non-thrombocytopenic purpura among patients with psoriasis was rare for all three databases and thrombocytopenic purpura was very rare. Across all databases, the treatment group of acitretin did not have enough outcomes for IRs to be calculated. ; Taken together, our results suggest that acitretin is most commonly used for psoriasis, and the outcome of purpura was rare in our populations of interest.