UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?

Hughes, Derralynn A; Aguiar, Patrício; Lidove, Olivier; Nicholls, Kathleen; Nowak, Albina; Thomas, Mark; Torra, Roser; ... Feriozzi, Sandro; + view all (2022) Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? Orphanet Journal of Rare Diseases , 17 (1) , Article 42. 10.1186/s13023-022-02181-4. Green open access

[thumbnail of Hughes_s13023-022-02181-4.pdf]
Preview
Text
Hughes_s13023-022-02181-4.pdf - Published Version

Download (1MB) | Preview

Abstract

BACKGROUND: Variable disease progression confounds accurate prognosis in Fabry disease. Evidence supports the long-term benefit of early intervention with disease-specific therapy, but current guidelines recommend treatment initiation based on signs that may present too late to avoid irreversible organ damage. Findings from the ‘PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease’ (PREDICT-FD) initiative included expert consensus on 27 early indicators of disease progression in Fabry disease and on drivers of and barriers to treatment initiation in Fabry disease. Here, we compared the PREDICT-FD indicators with guidance from the European Fabry Working Group and various national guidelines to identify differences in signs supporting treatment initiation and how guidelines themselves might affect initiation. Finally, anonymized patient histories were reviewed by PREDICT-FD experts to determine whether PREDICT-FD indicators supported earlier treatment than existing guidance. RESULTS: Current guidelines generally aligned with PREDICT-FD on indicators of renal involvement, but most lacked specificity regarding cardiac indicators. The prognostic significance of neurological indicators such as white matter lesions (excluded by PREDICT-FD) was questioned in some guidelines and excluded from most. Some PREDICT-FD patient-reported signs (e.g., febrile crises) did not feature elsewhere. Key drivers of treatment initiation in PREDICT-FD were: (A) male sex, young age, and clinical findings (e.g., severe pain, organ involvement), (B) improving clinical outcomes and preventing disease progression, and (C) a family history of Fabry disease (especially if outcomes were severe). All guidelines aligned with (A) and several advocated therapy for asymptomatic male patients. There was scant evidence of (B) in current guidance: for example, no countries mandated ancillary symptomatic therapy, and no guidance advocated familial screening with (C) when diagnosis was confirmed. Barriers were misdiagnosis and a lack of biomarkers to inform timing of treatment. Review of patient histories generally found equal or greater support for treatment initiation with PREDICT-FD indicators than with other guidelines and revealed that the same case and guideline criteria often yielded different treatment recommendations. CONCL

Type: Article
Title: Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13023-022-02181-4
Publisher version: https://doi.org/10.1186/s13023-022-02181-4
Language: English
Additional information: © 2022 BioMed Central Ltd. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Fabry disease, Guideline, Consensus, Renal, Cardiac, Neurological, Patient-reported outcome, Treatment initiation, Enzyme replacement therapy, Chaperone therapy
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10143789
Downloads since deposit
8Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item