Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?
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 irrever...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-02-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02181-4 |
| _version_ | 1818330648933302272 |
|---|---|
| author | Derralynn A. Hughes Patrício Aguiar Olivier Lidove Kathleen Nicholls Albina Nowak Mark Thomas Roser Torra Bojan Vujkovac Michael L. West Sandro Feriozzi |
| author_facet | Derralynn A. Hughes Patrício Aguiar Olivier Lidove Kathleen Nicholls Albina Nowak Mark Thomas Roser Torra Bojan Vujkovac Michael L. West Sandro Feriozzi |
| author_sort | Derralynn A. Hughes |
| collection | DOAJ |
| description | 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. Conclusions Wider 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. |
| first_indexed | 2024-12-13T13:07:18Z |
| format | Article |
| id | doaj.art-66f3ce4b9015408285a03a7d52421b7d |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-13T13:07:18Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-66f3ce4b9015408285a03a7d52421b7d2022-12-21T23:44:47ZengBMCOrphanet Journal of Rare Diseases1750-11722022-02-0117111510.1186/s13023-022-02181-4Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?Derralynn A. Hughes0Patrício Aguiar1Olivier Lidove2Kathleen Nicholls3Albina Nowak4Mark Thomas5Roser Torra6Bojan Vujkovac7Michael L. West8Sandro Feriozzi9Lysosomal Storage Disorders Unit, Institute of Immunity and Transplantation, Royal Free Hospital, Royal Free London NHS Foundation TrustInborn Errors of Metabolism Reference Center, North Lisbon Hospital CenterDepartment of Internal Medicine-Rheumatology, Croix Saint Simon HospitalDepartment of Nephrology, Royal Melbourne HospitalDepartment of Endocrinology and Clinical Nutrition, University Hospital Zurich and University of ZurichDepartment of Nephrology, Royal Perth HospitalInherited Renal Diseases Unit, Fundacio Puigvert, University Autónoma de BarcelonaDepartment of Internal Medicine, General Hospital Slovenj GradecDepartment of Medicine, Dalhousie UniversityDivision of Nephrology, Belcolle HospitalAbstract 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. Conclusions Wider 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.https://doi.org/10.1186/s13023-022-02181-4Fabry diseaseGuidelineConsensusRenalCardiacNeurological |
| spellingShingle | Derralynn A. Hughes Patrício Aguiar Olivier Lidove Kathleen Nicholls Albina Nowak Mark Thomas Roser Torra Bojan Vujkovac Michael L. West Sandro Feriozzi Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? Orphanet Journal of Rare Diseases Fabry disease Guideline Consensus Renal Cardiac Neurological |
| title | Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? |
| title_full | Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? |
| title_fullStr | Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? |
| title_full_unstemmed | Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? |
| title_short | Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease? |
| title_sort | do clinical guidelines facilitate or impede drivers of treatment in fabry disease |
| topic | Fabry disease Guideline Consensus Renal Cardiac Neurological |
| url | https://doi.org/10.1186/s13023-022-02181-4 |
| work_keys_str_mv | AT derralynnahughes doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT patricioaguiar doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT olivierlidove doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT kathleennicholls doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT albinanowak doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT markthomas doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT rosertorra doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT bojanvujkovac doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT michaellwest doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease AT sandroferiozzi doclinicalguidelinesfacilitateorimpededriversoftreatmentinfabrydisease |