Late-Stage Outcomes in Patients with Limb-Girdle Muscular Dystrophy (LGMD) Sarcoglycanopathy Subtypes: A Systematic Review
Author(s)
Sharanya Murty, MS, PhD1, Antoinette Cheung, MPH2, André Müller-York, MD1, Lavanya Sudharshan, MS1, Andrew Kennedy, BASc2, Shelagh Szabo, MSc2.
1Sarepta Therapeuatics, Inc, Cambridge, MA, USA, 2Broadstreet HEOR, Vancouver, BC, Canada.
1Sarepta Therapeuatics, Inc, Cambridge, MA, USA, 2Broadstreet HEOR, Vancouver, BC, Canada.
Presentation Documents
OBJECTIVES: Sarcoglycanopathies are severe, progressive subtypes of limb-girdle muscular dystrophy (LGMD), representing autosomal recessive subtypes LGMD2C/R5, LGMD2D/R3, LGMD2E/R4, and LGMD2F/R6. Ambulation loss is common in the sarcoglycanopathies. To better understand occurrence of later-stage outcomes, this study summarizes literature on the onset of respiratory or cardiac outcomes, or survival, by sarcoglycanopathy subtype.
METHODS: A systematic review following PRISMA guidelines was conducted. Aggregate and individual patient-level data (IPD) from cohort studies and case reports of sarcoglycanopathies (published 1996-2022) were extracted. Age at onset of respiratory and cardiac involvement (as defined by original investigators) and age at death were summarized, derived based on those experiencing each outcome of interest.
RESULTS: From 1,123 abstracts, 33 publications describing sarcoglycanopathies were identified; 10 reported IPD on respiratory assessments (n=131 patients; 55 with respiratory involvement), 14 described cardiac assessments (n=159; 63 with cardiac involvement), and 9 described mortality (n=114; 14 deaths). Across sarcoglycanopathy subtypes, median (interquartile range [IQR]) age at reported respiratory involvement was 25 (18-35) years. Variance was observed in reported age of respiratory involvement by subtype (16 [12-25], n=9 LGMD2C/R5; 19 [18-23], n=5 LGMD2F/R6; 25 [18-36], n=27 LGMD2E/R4; 35 [28-46] years, n=14 LGMD2D/R3). Median (IQR) age at cardiac involvement was 20 (14-32) years across sarcoglycanopathies. Cardiac involvement was reported at median (IQR) 20 (13-32) years in LGMD2E/R5 (n=51); data for other subtypes were limited (n=1 LGMD2C/R5, n=6 LGMD2D/R3, n=5 LGMD2F/R6). From studies that reported mortality, median (IQR) age at mortality was 32 (20-41) years (n=14); this was described among 6 LGMD2D/R3 and 8 LGMD2E/R4 patients.
CONCLUSIONS: This review indicates that, when they occur, respiratory and cardiac involvement in sarcoglycanopathies generally manifest in early adulthood. While studies reporting mortality were limited, available evidence suggests that respiratory and cardiac involvement may contribute. Limitations include potential publication biases from case reports, and inability to compare across sarcoglycanopathy subtypes due to sample sizes.
METHODS: A systematic review following PRISMA guidelines was conducted. Aggregate and individual patient-level data (IPD) from cohort studies and case reports of sarcoglycanopathies (published 1996-2022) were extracted. Age at onset of respiratory and cardiac involvement (as defined by original investigators) and age at death were summarized, derived based on those experiencing each outcome of interest.
RESULTS: From 1,123 abstracts, 33 publications describing sarcoglycanopathies were identified; 10 reported IPD on respiratory assessments (n=131 patients; 55 with respiratory involvement), 14 described cardiac assessments (n=159; 63 with cardiac involvement), and 9 described mortality (n=114; 14 deaths). Across sarcoglycanopathy subtypes, median (interquartile range [IQR]) age at reported respiratory involvement was 25 (18-35) years. Variance was observed in reported age of respiratory involvement by subtype (16 [12-25], n=9 LGMD2C/R5; 19 [18-23], n=5 LGMD2F/R6; 25 [18-36], n=27 LGMD2E/R4; 35 [28-46] years, n=14 LGMD2D/R3). Median (IQR) age at cardiac involvement was 20 (14-32) years across sarcoglycanopathies. Cardiac involvement was reported at median (IQR) 20 (13-32) years in LGMD2E/R5 (n=51); data for other subtypes were limited (n=1 LGMD2C/R5, n=6 LGMD2D/R3, n=5 LGMD2F/R6). From studies that reported mortality, median (IQR) age at mortality was 32 (20-41) years (n=14); this was described among 6 LGMD2D/R3 and 8 LGMD2E/R4 patients.
CONCLUSIONS: This review indicates that, when they occur, respiratory and cardiac involvement in sarcoglycanopathies generally manifest in early adulthood. While studies reporting mortality were limited, available evidence suggests that respiratory and cardiac involvement may contribute. Limitations include potential publication biases from case reports, and inability to compare across sarcoglycanopathy subtypes due to sample sizes.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO158
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Clinician Reported Outcomes
Disease
SDC: Rare & Orphan Diseases