Treatment needs and expectations for Fabry disease in France: development of a new Patient Needs Questionnaire.

BACKGROUND: Fabry disease (FD) is a rare, X-linked, inherited lysosomal disease caused by absent or reduced α-galactosidase A activity. Due to the heterogeneity of disease presentation and progression, generic patient-reported outcome (PRO) tools do not provide accurate insight into patients' daily lives and impact of disease specific treatments. Also, the French National Health Authority, (HAS) actively encourages a patient-centric approach to improve the quality of care throughout the patient journey. In response to this initiative, we aimed to develop and validate a specific, self-reported, Patient Needs Questionnaire for people living with Fabry disease to appraise patient needs and expectations towards their treatment (PNQ Fabry). This endeavour was led with the help of French patient associations (APMF & VML) and dedicated expert centres. PNQ Fabry was developed according to the FDA/EMA methodologies and best practices for the development of PRO tools in rare diseases. Our approach comprised of three steps, as follows: concept elicitation and item generation, item reduction, and final validation of the questionnaire through a two-stage survey. RESULTS: Intrinsic and extrinsic reliability was established, using a validated benchmark questionnaire. With the invaluable help of patient associations, we recruited a satisfactory population in this rare disease setting, to ensure robust participation to validate our PNQ (final number of questionnaires: 76). At the end of the process, a 26-item patient-reported questionnaire was obtained with excellent psychometric properties, exhibiting very satisfactory measurement outcomes for reliability and validity. The results of this initiative demonstrate that the PNQ Fabry is accurate, suitable and tailored to FD patients, as it addresses themes identified during patient interviews, that were further validated through statistical analyses of quantitative surveys. An ongoing phase IV study is using this tool. CONCLUSION: We believe the PNQ Fabry will be a reliable and insightful tool in clinical practice, to improve patient management in FD.

Clinical features of scleroderma patients with or without prior or current ischemic digital ulcers: post-hoc analysis of a nationwide multicenter cohort (ItinérAIR-Sclérodermie).

OBJECTIVE: Digital ulcers are the most frequent vascular manifestations of systemic sclerosis (SSc). Clinical features of patients with prior or current digital ulcers have not been extensively described. This cross-sectional analysis of a large multicenter cohort compared the characteristics of SSc patients with prior or current digital ulcers with those never affected. METHODS: Patients with prior/current digital ulcers or never affected were identified in the cohort of SSc patients enrolled in the French ItinérAIR-Sclérodermie registry. Rodnan skin scores, pulmonary function test results, and clinical and immunological data were analyzed to identify digital ulcerassociated clinical features. RESULTS: Of 599 SSc patients, 317 had prior or current digital ulcers. These patients were more frequently male, with impaired diffusing capacity for carbon monoxide (DLCO), and higher Rodnan skin scores than patients never affected by digital ulcers. In a multivariate analysis, male gender, early onset of SSc, increased duration of SSc, high Rodnan skin score, and presence of anti-topoisomerase I antibodies (anti-topo I) were associated with prior or current digital ulcers. Comparison of patients with current digital ulcers versus patients never affected indicated that affected patients had increased duration of SSc, impaired DLCO, increased Rodnan score, and younger age at onset of SSc. CONCLUSION: Male patients with early onset SSc, more severe skin fibrosis, impaired DLCO, and anti-topo I were most likely to exhibit prior or current digital ulcers. Confirmation of these results in a prospective longitudinal study may enable identification of patients at greatest risk of developing digital ulcers, facilitating management of this disabling complication.