An 18-month Low-interventional Study to Assess Joint Health in Haemophilia A and B Patients on Prophylaxis With Efmoroctocog Alfa or Eftrenonacog Alfa

Change From Baseline in HEAD-US Score for Hypertrophic Synovium

HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). The disease activity (synovitis) score rates the status of the hypertrophic synovium. Hypertrophic synovium is graded in three steps (0: absent/minimal; 1: mild/moderate \[score=1\], 2: severe \[score=2\]) based on the comprehensive evaluation of the joint recesses and the mean amount of synovial tissue contained in them.

Time frame: Baseline, month 6, 12 and 18

Change From Baseline in HEAD-US Score for Cartilage

HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). Concerning the articular cartilage, the damage is graded in five steps (0: normal; 1: echotexture abnormalities and focal loss involving \<25% of the target surface \[score=1\]; 2: partial/full-thickness loss of the cartilage involving at least 50% of the target surface \[score=2\]; 3: partial/full-thickness loss of the cartilage involving \>50% of the target surface \[score=3\]; 4: complete cartilage destruction or absent visualization of the articular cartilage on the target surface \[score=4\]).

Time frame: Baseline, month 6, 12 and 18

Change From Baseline in HEAD-US Score for Bone

HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). Damage of subchondral bone is scored using a three-grade scale (0: normal; 1: mild irregularities of the subchondral bone with/without initial osteophytes around the joint \[score=1\]; 2: deranged subchondral bone with/without erosions and presence of prominent osteophytes around the joint \[score=2\]).

Time frame: Baseline, month 6, 12 and 18

Change From Baseline in Total Hemophilia Joint Health Score (HJHS) at Month 18 (EOS)

The HJHS measures joint health, in the domain of body structure and function (i.e., impairment). The six index joints (elbows, knees, and ankles) will be examined and scored. The minimum score per joint is 0, the maximum score is 20. In addition, Gait is scored on a scale from 0 to 4 based on the number of skills that are not within the normal limits. The total score will be the sum of scores across all six joints plus the gait score (range from 0 to 124, with 0 being normal and 124 being the most severe disease).

Time frame: Baseline and month 18

Number of Target Joints

A target joint is defined as a joint with three or more spontaneous bleeds into the joint within a consecutive 6-month period. The study will evaluate the presence, resolution, recurrence, and new development of target joints.

Time frame: Baseline, month 6, 12 and 18

Location of Target Joints

A target joint is defined as a joint with three or more spontaneous bleeds into the joint within a consecutive 6-month period. The study will evaluate the presence, resolution, recurrence, and new development of target joints.

Time frame: Baseline, month 6, 12 and 18

Total Annualized Bleeding Rate (ABR)

For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location (e.g., muscle, joint, other), date of bleeding episode, dose (IU) and number of injections used to treat the bleed.

Time frame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period

Joint ABR

For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location, date of bleeding episode, dose (IU) and number of injections used to treat the bleed.

Time frame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period

Target Joint ABR

For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location, date of bleeding episode, dose (IU) and number of injections used to treat the bleed.

Time frame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period

Traumatic/Spontaneous ABR

For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location (e.g., muscle, joint, other), date of bleeding episode, dose (IU) and number of injections used to treat the bleed.

Time frame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period

PROMIS Physical Function/Activity Short Form 6b and 8a Scores

Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated system of reliable and precise measures of patient-reported health status. PROMIS measures cover physical, mental, and social health, use a 5-point Likert response scale and a recall period of the past 7 days. The Numeric Rating Scale measures for adults (6b) consist of a single item rating physical function on average over the past 7 days, ranging from 5 (without any difficulty) to 1 (unable to do). Lower scores mean a worse outcome. The Numeric Rating Scale measures for pediatric and parent proxy (8a) each consist of a single item rating physical activity on average over the past 7 days, ranging from 1 (no days) to 5 (6-7 days). Lower scores mean a worse outcome.

Time frame: Baseline and 18 months

PROMIS Pain Intensity 3a and 1a Scores

Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated system of reliable and precise measures of patient-reported health status. PROMIS measures cover physical, mental, and social health, use a 5-point Likert response scale and a recall period of the past 7 days. The Numeric Rating Scale measures for adults (3a) consist of a single item rating pain over the past 7 days from 1 (had no pain) to 5 (very severe). Higher scores mean a worse outcome. The Numeric Rating Scale measures for pediatric and parent proxy (1a) each consist of a single item rating pain over the past 7 days, ranging from 0 (no pain) to 10 (worst pain you can think of). Higher scores mean a worse outcome.

Time frame: Baseline and month 18

PROMIS Pain Interference Short Form 6a and 8a Scores

Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated system of reliable and precise measures of patient-reported health status. PROMIS measures cover physical, mental, and social health, use a 5-point Likert response scale and a recall period of the past 7 days. The Numeric Rating Scale measures (adult, pediatric, parent proxy) each consist of a single item rating pain interference with different activities over the past 7 days, ranging from 1 (not at all/never) to 5 (very much/almost always). Higher scores mean a worse outcome.

Time frame: Baseline and month 18

IPAQ-SF Scores

International Physical Activity Questionnaire - Short Form (IPAQ-SF). The IPAQ-SF is a validated, 7-day recall questionnaire measuring current levels of physical activity. Scoring of the IPAQ results in a continuous variable in the form of total MET-minutes per week, as well as categorization into high, moderate, or low physical activity level. Higher scores mean higher physical activity level (better outcome).

Time frame: Baseline and month 18