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.
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;
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);