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

Orphanet Journal of Rare Diseases

Albina Nowak¹  Bojan Vujkovac²  Olivier Lidove³  Michael L. West⁴  Kathleen Nicholls⁵  Mark Thomas⁶  Sandro Feriozzi⁷  Patrício Aguiar⁸  Roser Torra⁹  Derralynn A. Hughes^1,10 

[1] Department of Endocrinology and Clinical Nutrition, University Hospital Zurich and University of Zurich, Zurich, Switzerland;Department of Internal Medicine, Psychiatry University Hospital Zurich, Zurich, Switzerland;Department of Internal Medicine, General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia;Department of Internal Medicine-Rheumatology, Croix Saint Simon Hospital, Paris, France;Department of Medicine, Dalhousie University, Halifax, NS, Canada;Department of Nephrology, Royal Melbourne Hospital, Parkville, VIC, Australia;Department of Medicine, University of Melbourne - Parkville Campus, Parkville, VIC, Australia;Department of Nephrology, Royal Perth Hospital, Perth, WA, Australia;Division of Nephrology, Belcolle Hospital, Viterbo, Italy;Inborn Errors of Metabolism Reference Center, North Lisbon Hospital Center, Lisbon, Portugal;Medicine Department, Faculty of Medicine, Lisbon University, Lisbon, Portugal;Inherited Renal Diseases Unit, Fundacio Puigvert, University Autónoma de Barcelona, Barcelona, Spain;Lysosomal Storage Disorders Unit, Institute of Immunity and Transplantation, Royal Free Hospital, Royal Free London NHS Foundation Trust, Rowland Hill Street, NW3 2PF, London, UK;Department of Haematology, University College London, London, UK;

关键词: Fabry disease;    Guideline;    Consensus;    Renal;    Cardiac;    Neurological;    Patient-reported outcome;    Treatment initiation;    Enzyme replacement therapy;    Chaperone therapy;   

DOI  :  10.1186/s13023-022-02181-4

来源: Springer

【 摘 要 】

BackgroundVariable 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.ResultsCurrent 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.ConclusionsWider adoption of PREDICT-FD indicators at a national level could promote earlier treatment in Fabry disease. Clearer, more concise guidance is needed to harmonize treatment initiation in Fabry disease internationally.

【 授权许可】

CC BY