A Non-Interventional, Patient Registry For The Collection Of Pre-Defined Safety Data In Patients Prescribed Thelin (PROSE)

• Percentage of Participants With Elevated Liver Function Post-baseline [ Time Frame: Monthly up to 1 year ] [ Designated as safety issue: Yes ]
  Elevated liver function: greater than 3 times the upper limit of normal (>3 x ULN) alanine aminotransferase (ALT) and aspartase aminotransferase (AST) levels. Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses.
• Percentage of Participants With a Decrease in Hemoglobin Post-baseline [ Time Frame: Monthly up to 1 year ] [ Designated as safety issue: Yes ]
  Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses.
• Percentage of Participants With Increases in Total, Conjugated and Non-conjugated Bilirubin Post-baseline [ Time Frame: Monthly up to 1 year ] [ Designated as safety issue: Yes ]
  Total and conjugated bilirubin levels measured from blood, but indirect bilirubin calculated. Indirect bilirubin=Total bilirubin - Conjugated bilirubin. Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses.
• Duration of Exposure to Thelin [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
  Time between the first and last dose of Thelin. For participants who continued Thelin from TOPS (another study), the initial TOPS' Thelin start date was used.
• Adverse Events (AEs) by Seriousness and Relationship to Treatment [ Time Frame: Baseline up to year 1 ] [ Designated as safety issue: Yes ]
  Counts of participants who had AEs or treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Serious adverse events (SAEs) were reported from the time of informed consent. Relatedness to Thelin was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
• Clinical Status Since Last Visit [ Time Frame: Monthly up to 1 year ] [ Designated as safety issue: Yes ]
  Clinical status determined by status of pulmonary arterial hypertension (PAH) since last visit, reported as PAH remained stable, improved or deteriorated.
• Concomitant Medications [ Time Frame: Baseline, monthly up to 1 year ] [ Designated as safety issue: Yes ]
  Number of participants with concomitant medication usage reported by drug categories.
• Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results [ Time Frame: Baseline up to year 1 ] [ Designated as safety issue: Yes ]
  Counts of participants who had bleeding events or treatment-emergent bleeding events, defined as newly occurring or worsening after first dose. Serious bleeding events reported from time of informed consent. Relatedness to Thelin assessed by investigator (Yes/No). ERA usage: was participant taking Vitamin K antagonist? (Yes/No). INR: participant's prothrombin time (PT) ratio. Participants with multiple occurrences of an AE within a category were counted once within the category.
• Percentage of Participants Who Experienced Pulmonary Edema With the Presence of Veno-occlusive Disease [ Time Frame: Baseline up to year 1 ] [ Designated as safety issue: Yes ]
  The criteria used to determine whether participants had both pulmonary edema and veno-occlusive disease was at the discretion of the Investigator.

The Thelin Patient Safety Registry is a post-marketing program in the European Union (EU) that is designed to supplement the reporting of spontaneous adverse events (AE) and better characterize known and potential safety signals for Thelin. The registry is a secure, restricted access, electronic system which collects anonymous, pre-defined, patient-level data on demographic variables, safety monitoring measurements (i.e. liver function tests, haemoglobin and international normalized ratio (INR) measurements), concomitant medications, information on AEs and Thelin drug discontinuation. Regular review of the data is conducted to assess the frequency of identified safety risks and to monitor for the emergence of new safety signals at monthly pharmacovigilance meetings, quarterly signal detection meetings, and for each Periodic Safety Update Report (PSUR).

Non-probability sample

• All patients enrolled must meet the usual prescribing criteria for Thelin as per the Summary of Product Characteristics (SmPC) and are enrolled in the registry at the clinician's discretion.
• All prescribers are offered the opportunity to participate in the registry, assuming they have received appropriate educational materials

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document by the patient indicating that he/she (or a legally acceptable representative) has been informed of all pertinent aspects of the study is a requirement for inclusion.
• Additional inclusion criteria reflect the approved label for Thelin as outlined in the SmPC.

Exclusion Criteria:

• There are no specific exclusion criteria for enrollment in the Thelin Patient Safety Registry, with the exception of those reflected in the approved label for Thelin as outlined in the SmPC.