Incidence of Ultrasonographically Detected Articular Damage in Initially Healthy Joints of Patients With Hemophilia A Receiving Prophylactic Treatment With Emicizumab

Incidence of Ultrasonographically Detected Articular Damage in Initially Healthy Joints of Patients With Hemophilia A Receiving Prophylactic Treatment With Emicizumab. A Prospective Observational Study

Introduction: Prophylaxis with emicizumab has substantially improved hemorrhagic control in hemophilia A. However, the longitudinal incidence of ultrasonographically detected articular damage in initially healthy joints remains insufficiently characterized.

Objective: To estimate the incidence of ultrasonographically detected articular damage in initially healthy joints among patients with hemophilia A receiving prophylaxis with emicizumab and to explore its association with relevant clinical variables.

Methods: A prospective, longitudinal, observational study will be conducted in approximately 70 patients with hemophilia A receiving emicizumab, with an estimated recruitment of approximately 270 initially healthy joints. The study is purely observational and does not involve evaluation of the investigational product nor modification of the therapeutic regimen; dosing, administration intervals, and all clinical decisions regarding emicizumab will be determined exclusively at the discretion of the treating hematologist. Assessments will be performed at baseline and at 12 and 24 months. The unit of analysis will be the joint, including elbows, knees, and ankles without ultrasonographic evidence of articular damage and without a history of clinically evident hemarthrosis at study entry.

The primary endpoint will be the occurrence of incident ultrasonographically detected articular damage, assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol. Secondary outcomes will include clinical joint health assessed by the Hemophilia Joint Health Score (HJHS), version 2.1; the frequency of joint hemarthroses measured by the annualized joint bleeding rate (AJBR); and habitual physical activity levels evaluated through age-specific validated questionnaires. Statistical analyses will account for intra-patient correlation among joints.

Expected Results: A low to moderate incidence of ultrasonographically detected articular damage in initially healthy joints is anticipated during follow-up, providing clinically relevant information regarding structural joint preservation in patients with hemophilia A receiving emicizumab prophylaxis.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophilia
• Intervention / Treatment: Other: Hemophilia patients

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Rubén Cuesta-Barriuso, PhD; Phone Number: 0034 985103386; Email: cuestaruben@uniovi.es

Study Locations

• Spain
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33006
      • Universidad de Oviedo
      • Contact: Ruben Cuesta-Barriuso, PhD; Phone Number: 0034 985 103 386; Email: cuestaruben@uniovi.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with hemophilia A receiving prophylactic treatment with emicizumab

Description

Inclusion Criteria:

• Confirmed diagnosis of hemophilia A;
• Receiving prophylactic treatment with emicizumab (Hemlibra®) according to routine clinical practice;
• Age ≥10 years at the time of study enrollment;
• Absence of ultrasonographic joint damage in at least one of the evaluated joints (elbows, knees, or ankles), defined as HEAD-US = 0 at baseline assessment;
• No documented history of clinically evident hemarthrosis in the corresponding joints from initiation of emicizumab prophylaxis to the study baseline evaluation;
• Ability to understand and complete study procedures (interviews, questionnaires, and clinical assessments), in accordance with the participant's age; and
• Provision of written informed consent; for minors, written informed consent from parents or legal guardians and assent from the minor participant, in accordance with applicable regulations.

Exclusion Criteria:

• Presence of ultrasonographic joint damage (HEAD-US ≥1) in all evaluated joints at the baseline visit;
• Documented history of clinically evident hemarthrosis in the joints under study;
• Prior major orthopedic surgery or arthroplasty in the evaluated joints;
• Presence of concomitant musculoskeletal pathology unrelated to hemophilia that could interfere with joint assessment (e.g., inflammatory arthritis, recent severe trauma);
• Inability to complete the planned 24-month follow-up or to undergo study assessments;
• Concurrent participation in another interventional study that could interfere with the joint health variables under evaluation; and
• Any clinical or social condition that, in the investigator's judgment, could compromise participant safety or the validity of the study data.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational group; Patients with hemophilia A receiving prophylactic treatment with emicizumab	Other: Hemophilia patients; A prospective, longitudinal, observational study will be conducted in patients with hemophilia A receiving prophylaxis with emicizumab, with a 24-month follow-up period. Three assessments will be performed: at baseline, 12 months, and 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Ultrasonographically Detected Articular Damage in Elbows, Knees, and Ankles	Ultrasonographically detected articular damage will be assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol through standardized musculoskeletal ultrasound examination. This scoring system evaluates three structural domains per joint: synovial (hypertrophy and effusion), cartilage, and bone. Each joint is assigned an ordinal score ranging from 0 (no abnormalities) to a maximum of 8 points, derived from the combined assessment of the synovial, cartilaginous, and osseous domains. The HEAD-US protocol enables detection of subclinical joint damage and early structural changes, even in the absence of clinically evident hemarthrosis.Scree	Baseline visit, at 12 months, and at 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Clinical Joint Health in Knees, Ankles, and Elbows	Clinical joint health will be assessed using the Hemophilia Joint Health Score, version 2.1 (HJHS 2.1). This instrument evaluates eight items per joint: swelling (edema), duration of swelling, pain, muscle atrophy, crepitus, strength deficit, loss of range of motion, and joint deformity. Additionally, it includes a global gait assessment scored from 0 to 4. Each item is rated on an ordinal scale according to the instrument's predefined criteria, yielding a per-joint score ranging from 0 to 20 and a total score ranging from 0 to 124. Higher scores indicate worse clinical joint health.	Baseline visit, at 12 months, and at 24 months.
Measurement of Joint Hemorrhagic Phenotype	This variable will be assessed using the Annualized Joint Bleeding Rate (AJBR), calculated as the number of hemarthroses occurring during the observation period divided by the total days of follow-up and multiplied by 365.25. The AJBR will be calculated both globally and on a per-joint basis, based on systematically recorded bleeding events obtained through structured clinical interviews.	Baseline visit, at 12 months, and at 24 months.
Measurement of Physical Activity Level in patients under 18 years of age	This variable will be assessed using the Physical Activity Questionnaire for Adolescents (PAQ-A). The PAQ-A consists of nine items evaluating participation in various types of physical and sports activities; frequency of activity during physical education classes; activity during recess and leisure time; after-school activity; weekend activity; and overall level of habitual physical activity. Each item is scored on a 5-point Likert scale (1 to 5), and the final score corresponds to the mean of all items. Higher scores indicate a greater level of habitual physical activity.	Baseline visit, at 12 months, and at 24 months.
Measurement of Physical Activity Level in Adult Patients	This variable will be assessed using the International Physical Activity Questionnaire - Long Form (IPAQ-LF). The IPAQ-LF captures physical activity across four domains: work-related physical activity, active transportation, domestic and household activities, and leisure-time physical activity. Within each domain, the time spent in vigorous-intensity activity, moderate-intensity activity, and walking is recorded, allowing for the calculation of total energy expenditure expressed in MET-minutes per week (MET-min/week).	Baseline visit, at 12 months, and at 24 months.
Measurement of Treatment Adherence	This variable will be assessed using the Torres questionnaire for treatment adherence in hemophilia. This hemophilia-specific instrument evaluates five dimensions: disease awareness, perceived sequelae, treatment-related difficulties, physician-patient relationship, and hemorrhagic processes. Higher scores indicate greater adherence within the corresponding domain.	Baseline visit, at 12 months, and at 24 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Age	This variable, used to describe the sample and control for potential confounding factors, will be measured as a quantitative variable (in years)	Screening visit
Measurement of Hemophilia Severity	This variable, used to describe the sample and control for potential confounding factors, will be measured as an ordinal variable (severe / moderate / mild).	Screening visit
Measurement of Inhibitor Status	This variable, used to describe the sample and control for potential confounding factors, will be measured as a dichotomous variable (yes / no)	Screening visit
Measurement of Duration of Emicizumab Prophylaxis	This variable, used to describe the sample and control for potential confounding factors, will be measured as a quantitative variable (in years).	Screening visit

Collaborators and Investigators

• Sponsor: Investigación en Hemofilia y Fisioterapia

Study record dates

Study Major Dates

• Study Start (Estimated): February 27, 2026
• Primary Completion (Estimated): May 3, 2026
• Study Completion (Estimated): May 3, 2028

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: prophylaxis; emicizumab; Joint damage; joint preservation
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A
• Other Study ID Numbers: HEmoJoint

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No