REAL-CARE: Real-world Effectiveness of Iptacopan in Italian Patients With Paroxysmal Nocturnal Hemoglobinuria

Socio-demographic and clinical variables of Paroxysmal Nocturnal Hemoglobinuria population

Descriptive measures of the socio-demographic variables, proportion of PNH cells, clinical symptoms, laboratory parameters, concomitant diseases and treatments and outcomes of PNH patients at iptacopan initiation.

Time frame: date of iptacopan start, day 0

Absolute change in Hb level post iptacopan initiation

24-month absolute change in Hb level post iptacopan initiation

Time frame: date of iptacopan start (day 0), 24 months

Proportion of patients who didn't need RBC transfusion

24-month proportion of patients who didn't need RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, post iptacopan initiation

Time frame: 24 months

Proportion of patients with Hb levels ≥ 12 g/dL AND no RBC transfusion

12- and 24-month proportion of patients with Hb levels ≥ 12 g/dL AND no RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, between Day 14 and month 12 or month 24

Time frame: 12 month, 24 month

Proportion of patients with change in Hb levels ≥ 2 g/dL post iptacopan initiation AND no RBC transfusion

12- and 24-month proportion of patients with change in Hb levels ≥ 2 g/dL post iptacopan initiation AND no RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, between Day 14 and month 12 or month 24

Time frame: 12 month, 24 month

Average number of RBC transfusion

Average number of RBC transfusion, prescribed as per local requirement and based on Investigator's judgment, per patient during 12- and 24-months post iptacopan initiation

Time frame: 12 months and 24 months

Percentage change in LDH level post iptacopan initiation

12- and 24-month percentage change in LDH level post iptacopan initiation.

Time frame: date of iptacopan start (day 0), month 12, month 24

Change in reticulocyte count post iptacopan initiation.

12- and 24-month change in reticulocyte count post iptacopan initiation.

Time frame: date of iptacopan start (day 0), month 12, month 24

Absolute change in bilirubin level post iptacopan initiation.

12- and 24-month absolute change in bilirubin level post iptacopan initiation.

Time frame: date of iptacopan start (day 0), month 12, month 24

Frequency of adverse events (AE) and serious adverse events (SAE) over 12 and 24 months of follow-up

Frequency of adverse events (AE) and serious adverse events (SAE) over 12 and 24 months of follow-up post iptacopan initiation

Time frame: 12 months and 24 months

Proportion of BTH occurrence

Proportion of Breakthrough Hemolysis (BTH) occurrence over 12 and 24 months of follow-up post iptacopan initiation

Time frame: 12 months and 24 months

Type and proportion of Infections occurrence over 12 and 24 months of follow-up

Type and proportion (count and percentage) of Infections occurrence over 12 and 24 months of follow-up post iptacopan initiation

Time frame: 12 months and 24 months

Type and proportion of major adverse vascular events (MAVEs) occurrence

Type and proportion of major adverse vascular events (MAVEs) occurrence over 12 and 24 months of follow-up post iptacopan initiation

Time frame: 12 months and 24 months

Type and proportion of new comorbidities

Type and proportion of new comorbidities occurred within 12 and 24 months of follow-up post iptacopan initiation

Time frame: 12 months and 24 months

Type and proportion of concomitant medications newly prescribed

Type and proportion of concomitant medications newly prescribed during 12 and 24 months of follow-up post iptacopan initiation

Time frame: 12 months and 24 months

Absolute change in Medication Adherence Report Scale - 5 item (MARS-5) scores

The MARS-5 questionnaire is a validated self-report questionnaire developed to assess patient adherence to prescribed medication, focusing on both intentional and unintentional non-adherence. It consists of five items, each rated on a 5-point Likert Scale, from 0 ("Always") to 5 ("Never"). Items evaluate behaviors such as forgetting to take medications, altering the dose or stopping the treatment. The total score ranges from 5 to 25, with higher scores indicating better adherence to treatment.

Time frame: date of iptacopan start (day 0), month 12 and month 24

Absolute change from iptacopan initiation in PROMIS-29+2 score.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Profile-29+2 is a validated standardized patient reported outcome measure to assess generic health-related quality of life. The questionnaire covers the following nine health domains: Physical function, Anxiety, Depression, Fatigue, Sleep disturbance, Ability to participate in social roles and activities, Pain interference, Cognitive function and Pain intensity. The recall period for all items is the past 7 days. Each of the first eight domains is assessed through 4 items using a 5-point Likert scale. Pain intensity is measured with a single item on an 11-point numeric rating scale from 0 ("no pain") to 10 ("worst imaginable pain"). Each domain is scored separately, with T-scores used to represent the severity or level of functioning in each area. Higher scores can indicate either better health (e.g., physical function) or greater severity of symptoms (e.g., anxiety, depression).

Time frame: date of iptacopan start (day 0), month 12 and month 24

Absolute change from iptacopan initiation in WPAI:SHP score.

Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a validated patient-reported outcome measure designed to assess the impact of a specific health problem on work and daily activities. In this study, the questionnaire has been customized for PNH. It includes six questions grouped into four key domains: Absenteeism (work time missed due to PNH), Presenteeism (impairment while working due to PNH), Overall work productivity loss (combined absenteeism and presenteeism), Activity impairment (impact of PNH on regular daily activities outside of work). The recall period is the past 7 days. Responses are used to calculate the percentage of work time missed and the level of impairment experienced by the patient. Higher scores represent greater impairment and reduced productivity.

Time frame: date of iptacopan start (day 0), month 12 and month 24

Number of hospitalizations, emergency room visits, and hospital-based outpatient visits attributable to the management of AEs related to the study treatment

Healthcare resources utilization: The number of hospitalizations, emergency room visits, and hospital-based outpatient visits attributable to the management of adverse events (AEs) related to the study treatment will be documented.

Time frame: Up to 24 months