Aim: To develop recommendations for haemophilic arthropathy management in people with haemophilia adapted to the Japanese medical setting.

Methods: Using an informal consensus method, a steering group of 14 clinical experts (orthopaedic surgeon, physiatrist/physiotherapist, paediatrician, and haematologist) developed 40 literature-based statements and 18 sub-statements related to haemophilic arthropathy management in people with haemophilia. A panel of 30 experts was surveyed by email and the level of agreement with each statement/sub-statement: strong consensus, consensus, non-consensus, and strong non-consensus, was determined.

Results: The survey was completed by 27/30 respondents. Strong consensus/consensus was reached for 39 statements/sub-statements, non-consensus/strong non-consensus was reached for four (all related to pain assessment and management), and consensus/non-consensus was not reached for 15.

Conclusion: Routine evaluations (physical function, joint ultrasound, quality of life (QOL), and psychological), activities (rehabilitation therapy such as physical therapy, aerobic exercise, and sports), appropriate pain management, and proactive screening for osteoporosis are important when managing haemophilic arthropathy in people with haemophilia.

Developing variant-specific therapies for genetic diseases is not scalable, particularly for disorders with extensive allelic heterogeneity such as hemophilia B, caused by variants in the F9 gene encoding coagulation factor IX (FIX). Instead of correcting individual variants, we investigated a gain-of-function strategy using CRISPR–Cas9–based cytosine base editing to introduce the hyperactive R338Q (Shanghai) variant (c.1151G>A) into the endogenous F9 locus. This substitution enhances intrinsic tenase activity without increasing protein expression. An optimized base editor delivered via adeno-associated virus (AAV) achieved >60% target-site conversion in human cells and knock-in mouse models, resulting in increased FIX activity across multiple patient-derived F9 variants in knock-in models. Lipid nanoparticle (LNP) delivery also enabled efficient in vivo editing, while supporting repeat dosing and controlled editor exposure. These approaches resulted in a three- to sixfold increase in circulating FIX activity. Together, this gain-of-function genome-editing strategy provides a scalable and physiologically regulated therapeutic framework for hemophilia B.