Long-term risk factors for hemophilic arthropathy in patients with severe hemophilia A: a 36-year retrospective cohort study

Abstract

Hemophilic arthropathy (HA) is a major cause of disability in patients with severe hemophilia A. However, long-term data describing progression to advanced radiographic HA across major joint sites remain limited. We investigated risk factors for progression to advanced HA over extended follow-up. We conducted a retrospective cohort study of inhibitor-negative patients with severe hemophilia A followed at our institute between 1984 and 2020. Bilateral elbows, knees, and ankles were evaluated (six joints per patient). HA progression was defined as reaching Arnold–Hilgartner stage ≥ IV. Time to progression was analyzed using Cox proportional hazards models with cluster-robust standard errors, with participant as the clustering variable, to account for within-participant correlation across joints. Covariates included joint site, Arnold–Hilgartner stage at initiation of regular prophylaxis, age at first visit to our institute, prophylaxis status at the first visit, and laterality. The cohort included 109 patients (mean age at first visit to our institute, 14.3 years). At the first visit, Arnold–Hilgartner stage ≥ I changes were present in 15% of elbows (29/200), 8% of knees (16/200), and 27% of ankles (51/186). Across 583 joints and 8,634 joint-years of follow-up, 94 joints progressed to stage ≥ IV (10.9 per 1,000 joint-years of follow-up). In multivariable analysis, baseline radiographic status at the start of regular prophylaxis was strongly associated with progression (vs stage 0: stage I HR 14.95; stage II HR 11.84; stage III HR 34.47). Patients already receiving regular prophylaxis at the first visit had a lower risk of progression (HR 0.54). After adjustment, joint-site differences were not evident, and the independent association of age at first visit to our institute with progression was not estimated with sufficient precision. Baseline radiographic status at initiation of regular prophylaxis was strongly associated with long-term progression to advanced radiographic HA. These findings support initiating regular prophylaxis before radiographic joint changes become established.