Real world outcomes of Fabry disease in Italian excellence centers: the ground study

A better understanding of Fabry Disease (FD) in terms of diagnostic journey, patient profile and use of available treatments remains topical. The Global buRden and treatment trajectOries in Italian patients with Fabry disease: a retrospective longitUdinal and cross-sectioNal study-GROUND was designed to provide a comprehensive overview of a real-world FD Italian cohort.

This was a retrospective, multicenter, longitudinal and cross-sectional study of adult FD patients of either sex with ≥ 3 years of follow-up. Severe/fatal events from birth to last visit was the composite primary outcome. Secondary outcomes were disease progression measured by FAbry STabilization indEX (FASTEX); disease activity assessed by clinically significant events/FD related symptoms; time from first manifestation to diagnosis; treatment trajectories.

199 patients, 73 males and 126 females, 169 classic and 30 late-onset phenotypes, were enrolled at 8 Italian centers. Mean time from first FD symptom to diagnosis was 5.03 years (range 0.00-43.90), with a median of 0.64 years (range 0-19.29) from diagnosis to start of FD specific treatment. Initial manifestations were chronic pain (18.1%), angiokeratomas (13.1%), acroparesthesia and abdominal pain (12.5%), or left ventricular hypertrophy (LVH) (8.5%). 143 missense/nonsense GLA variants were identified. 82% patients were actively treated with one of the FD specific therapies, 24% had switched ≥ 1 treatment, while 5% had definitively stopped treatment. The primary outcome was experienced by 31.7% of patients for a total of 85 severe/fatal events, mainly in the treated cohort: 20.6% had a cardiac event, 11.1% a cerebral event 7.5% patients experienced a renal event, while fatal events occurred in 7 patients (3.5%). 88.9% reported ≥ 1 clinically significant event, with detection/worsening of LVH being the most common (41.2%). Estimated Glomerular Filtration rate (eGFR) slopes in last 1-3 years of follow-up were - 2.07 ml/min/m² (SE: 1.38) and - 0.76 and - 2.07 ml/min/m² (SE: 1.75) in classic males and females, respectively. Long-term FASTEX identified 31.1% of patients as being unstable.

Even though FD patients were promptly treated, severe clinical events occurred in about 30%, mainly classic males, highlighting the need for sensitive tools assessing outcomes and novel therapeutic options.