Table 1.
Characteristics of included studies
| Author (year) [country] | Study design | Site(s)/data source(s) | Study period | Sample, n (age) | Case ascertainment | Pharmacological intervention(s) | n (%) exposed | Dose, mean | Duration of exposure, mean (SD) |
| Barber et al. (2013) [US] [15] | Retrospective cohort study | MD STARnet (US, multi-centre) | 1982–2010 | 462 patients with DMD (mean age: NR, range: NR) | NRa | Glucocorticoids (DFZ, PDN, or PRED) | 291 (63%) | NR | 4.1 (3.4) years |
| Barnard et al. (2020) [US] [52] | Prospective cohort study | ImagingDMD (US, multi-centre) | 2010–NR | 160 patients with DMD (mean age: 8 years, range: 4–18 years) | NR | Glucocorticoids (DFZ, PDN, or PRED) | 118 (74%) | NR | NR |
| Ataluren | 19 (12%) | NR | NR | ||||||
| Eteplirsen | 15 (9%) | NR | NR | ||||||
| Bello et al. (2015) [*] [12] | Prospective cohort study | CINRG DNHS (multi-country, multi-centre) | NR–2013 | 340 patients with DMD (mean age: 14 years, range: 2–28 years) | NRa | Glucocorticoids (DFZ, PDN, or PRED) | 277 (81%) | Regimen-specific (see article for details) | 4.0 years (3.3) (range: 0.1–18.3) years |
| Bello et al. (2015) [*] [16] | Prospective cohort study | CINRG DNHS (multi-country, multi-centre) | NR | 340 patients with DMD (mean age: NR, range: 2–28 years) | NRa | Glucocorticoids (agents NR) | 252 (74%) | NR | >1 year (before loss of ambulation) |
| Bello et al. (2016) [*] [17] | Prospective cohort study | CINRG DNHS (multi-country, multi-centre) | 2006–2009 | 212 patients with DMD (mean age: NR, range: NR) | NRa | Glucocorticoids (DFZ, PDN, or PRED) | 157 (74%) | NR | >1 year (before loss of ambulation) |
| Bello et al. (2016) [*] [18] | Prospective cohort study | CINRG DNHS (multi-country, multi-centre) | NR | 109 patients with DMD (mean age: NR, range: NR) | NRa | Glucocorticoids (agents NR) | NR | NR | >1 year (before loss of ambulation) |
| Biggar et al. (2001) [CA] [19] | Retrospective cohort study | The Bloorview MacMillan Children’s Center (Toronto, CA) | 1993–1999 | 54 patients with DMD (mean age: 12 years, range: 7–15 years) | Age at onset of symptoms (<5 years of age), male sex, proximal muscle weakness, increased serum creatine kinase levels, and muscle biopsy and/or genetic testing | Glucocorticoids (DFZ) | 30 (56%) | Initial dose •0.9 mg/kg/day At 10 years of age • 0.76 (0.19) mg/kg/day At 15 years of age • 0.61 (0.20) mg/kg/day | 3.2 (1.3) years |
| Bonifati et al. (2006) [IT] [20] | Retrospective cohort study | Database (name and location NR) | NR | 48 patients with DMD (mean age: 8 years, range: 4–12 years) | Genetic testing | Glucocorticoids (DFZ or PDN) | 48 (100%) | First year of treatment •DFZ: 0.9 mg/kg/day •PDN: 0.75 mg/kg/day Second year of treatment (until loss of ambulation) •DFZ: 1.5 mg/kg every other day •PDN: 1.8 mg/kg/day every other day | NR |
| Chen et al. (2020) [CN] [21] | Retrospective cohort study | The First Affiliated Hospital of Sun Yat-sen University (Guangzhou, CN) | NR | 326 patients with DMD (mean age: 8 years, range: 4–12 years) | Genetic testing | Glucocorticoids (DFZ or PDN) | 144 (44%) | NR | NR |
| Ciafaloni et al. (2016) [US] [22] | Retrospective cohort study | MD STARnet (US, multi-centre) | 1982–2009 | 825 patients with DMD (mean age: NR, range: NR) | NRa | Glucocorticoids (agents NR) | 808 (49%) | NR | NR |
| Fischmann et al. (2012) [CH] [53] | Prospective cohort study | NR | NR | 20 patients with DMD (mean age: 11 years, range: 5–23 years) | Genetic testing | NR | NR | NR | NR |
| Flanigan et al. (2013) [US] [23] | Retrospective cohort study | The United Dystrophinopathy Cohort (US, multi-centre) | NR | 239 patients with DMD (mean age: NR, range: NR) | Age of onset of symptoms, disease progression characteristics, and genetic testing | Glucocorticoids (agents NA) | 137 (57%) | NR | NR |
| Godi et al. (2016) [IT] [54] | Prospective cohort study | Neuromuscular centre (name and location NR, IT) | 2009–NR | 26 patients with DMD (median age: 9 years, range: 5–12 years) | Clinical history of early onset, progressive muscle weakness, increased serum creatine kinase levels, muscle biopsy and genetic testing | Glucocorticoids (agents NR) | 25 (96%) | NR | NR |
| Haber et al. (2021) [US] [24] | Retrospective cohort study | MD STARnet (US, multi-centre) | 1982–2012 | 358 patients with DMD (mean age: NR, range: NR) | NRa | Glucocorticoids (DFZ or PDN) | 226 (63%) | NR | 3.10 (SD: 2.84) years |
| Houde et al. (2008) [CA] [25] | Retrospective cohort study | The multidisciplinary Neuromuscular Clinic of the Marie-Enfant Rehabilitation Centre (Montreal, CA) | NR | 79 patients with DMD (mean age: 11 years; range: NR) | Muscle biopsy and/or genetic testing | Glucocorticoids (DFZ) | 37 (47%) | Initial dose •0.9 mg/kg per day (adjusted according to evolution or side effects to a maximum of 1 mg/kg) At last visit •0.69 (SD: 0.20) mg/kg | 66 months |
| ACE inhibitors (agents NR) | 30 (38%) | NR | NR | ||||||
| Hufton et al. (2017) [UK] [26] | Retrospective cohort study | Neuromuscular clinic (name and location NR, UK) | 2005–2014 | 69 patients with DMD (mean age: 10 years; range: 5–18 years) | Genetic testing | Glucocorticoids (agents NA) | 57 (83%) | NR | NR |
| Humbertclaude et al. (2012) [FR] [27] | Retrospective cohort study | The French dystrophinopathy database (UMD–DMD France) (FR, multi-centre) | NR | 278 patients with DMD (mean age: 11 years; range: NR) | Genetic testing and loss of ambulation before 13 years of age | Glucocorticoids (agents NA) | 0 (0%) | NA | NA |
| Kim et al. (2015) [US] [28] | Retrospective cohort study | MD STARnet (US, multi-centre) | 1982–2011 | 477 patients with DMD (mean age: 7 years; range: NR) | NRa | Glucocorticoids (DFZ and/or PDN) | 220 (46%) | NR | 3.4 years |
| King et al. (2007) [US] [29] | Retrospective cohort study | The Ohio State University (Columbus, US) | 2000–2003 | 143 patients with DMD (mean age: 16 years; range: 1–40 years) | Clinical presentation and genetic testing | Glucocorticoids (DFZ and/or PDN) | 75 (52%) | •DFZ: 0.9 mg/kg/day •PDN: 0.75 mg/kg/day | 8.04 (5.2) (range: 0.5–18.5) years |
| Koeks et al. (2017) [*] [30] | Retrospective cohort study | The TREAT-NMD global DMD database (multi-national, multi-centre) | 2007–2013 | 5,345 patients with DMD (mean age: NR, range: NR) | Genetic testing | Glucocorticoids (DFZ, PDN, or PRED) | Current use •2,658 (50%) Past use •522 (10%) | NR | NR |
| Kosac et al. (2022) [RS] [31] | Retrospective cohort study | •Clinic for Neurology and Psychiatry for Children and Youth (Belgrade, RS) •Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic” (Belgrade, RS) | NR | 95 patients with DMD (mean age: 16 years, range: NR) | Genetic testing | Glucocorticoids (DFZ or PRED) | 73 (77%) | NR | >1 year |
| Mazzone et al. (2013) [IT] [32] | Retrospective cohort study | IT, multi-centre | 2008–2009 | 113 patients with DMD (mean age: 8 years, range: 4–17 years) | Genetic testing | Glucocorticoids (DFZ or PRED) | Intermittent glucocorticoids •40 (35%) Daily glucocorticoids •67 (59%) | Intermittent regimen •DFZ: 0.9 mg/kg/day •PDN: 0.75 mg/kg/day Daily regimen: •DFZ: 0.9 mg/kg/day •PDN: 0.75 mg/kg/day | NR |
| McDonald et al. (2018) [*] [33] | Prospective cohort study | CINRG DNHS (multi-country, multi-centre) | 2006–2009; 2012–2016 | 403 patients with DMD (mean: 11 years, range: 2–28 years) | Clinical and molecular diagnostic picture consistent with typical DMD (see article for details) | Glucocorticoids (DFZ, PDN, and/or PRED) | 330 (82%) | NR | Regimen-specific (see article for details) |
| McDonald et al. (2022) [*] [34] | Indirect treatment comparison study | •Study 019 (open-label study; multi-country, multi-centre [NCT01557400]) •CINRG DNHS (prospective cohort study; multi-country, multi-centre [NCT00468832]) | •Study 019: NR •CINRG DNHS: 2006–2016 | 120 patients with DMD (distribution of age NR) | •Study 019: NRa •CINRG DNHS: NRa | Ataluren | 60 (50%) | 40 mg/kg/day | NRa |
| Mendell et al. (2016) [US] [35] | Indirect treatment comparison study | •Study 201 (RCT; US; single-centre [NCT01396239]) •Study 202 (open label, multiple dose extension study; US, multi-centre) | NR | 25 patients with DMD (mean age: 9 years, range: 7–12 years) | Genetic testing | Eteplirsen | 12 (48%) | 30mg/kg or 50mg/kg | ≥3 years |
| Glucocorticoids (DFZ, PDN, or PRED) | 25 (100%) | NR | ≥24 weeks | ||||||
| Mendell et al. (2021) [US] [36] | Indirect treatment comparison study | •Study 201 (RCT; US; single-centre [NCT01396239]) •Study 202 (open label, multiple dose extension study; US, multi-centre [NCT01540409]) •The Italian Telethon and Leuven registries (multi-country, multi-centre) | NR | 23 patients with DMD (mean age: 9 years, range: 7–12 years) | NRa | Eteplirsen | 12 (52%) | •30mg/kg or 50mg/kg | ≥4 years |
| Glucocorticoids (DFZ and/or PDN) | 25 (100%) | •DFZ: 0.9 mg/kg/day •PDN: 0.75 mg/kg/day | NR | ||||||
| Mercuri et al. (2020) [*] [37] | Indirect treatment comparison study | •The STRIDE Registry (multi-country, multi-centre) •CINRG DNHS (multi-country, multi-centre) | •The STRIDE Registry: 2006–2018 •CINRG DNHS: NRa | 362 patients with DMD (mean age: 11 years, range: 2–27 years) | NRa | Ataluren | 181 (50%) | NRa | 632 (363) (range: 5–1,453) days |
| Glucocorticoids (agents NR) | NR | NR | •The STRIDE Registry: 995 (1,184) days •CINRG DNHS: 978 (1,166) days | ||||||
| Mitelman et al. (2022) [*] [38] | Indirect treatment comparison study | •Study 201 (RCT; US; single-centre [NCT01396239]) •Study 202 (open label, multiple dose extension study; US, multi-centre •Study 405 (retrospective cohort study; US, multi-centre) •CINRG DNHS (prospective cohort study; multi-country, multi-centre [NCT00468832]) | NR | 83 patients with DMD (mean age: 8 years, range 5–15 years) | •Study 201/202: NRa •Study 405: NRa •CINRG DNHS: NRa | Eteplirsen | 12 (14%) | 30 or 40 mg/kg/week | 5.72 (SD: 0.90) (range: 4.13–6.88) |
| Glucocorticoids (DFZ or PDN) | 27 (100%) | NR | NR | ||||||
| Naarding et al. (2020) [NL] [55] | Prospective cohort study | Leiden University Medical Center (LUMC) (Leiden, the Netherlands)b | 2013–2016 | LUMC: 22 patients with DMD (median age: 9 years, IQR: 7–12 years) | Genetic testing | Glucocorticoids (DFZ or PDN) | LUMC: 18 (82%) | NR | NR |
| Pane et al. (2014) [IT] [39] | Prospective cohort study | IT, multi-centre | 2008–2013 | 96 patients with DMD (mean age: 8 years, range: 5–13 years) | Genetic testing | Glucocorticoids (DFZ or PDN) | 91 (95%) | Regimen-specific (see article for details) | NR |
| Rooney et al. (2020) [US] [56] | Prospective cohort study | ImagingDMD (US, multi-centre) | 2011–2018 | 104 patients with DMD (median age: 9 years, range: 4–17 years) | NRa | Glucocorticoids (DFZ, PDN, or PRED) | 90 (87%) | NR | NR |
| Schara et al. (2001) [DE] [40] | Retrospective cohort study | NR | NR | 26 patients with DMD (mean age: NR, range: NR) | NR | Glucocorticoids (DFZ) | 13 (50%) | •0.9 mg/kg/day | NR |
| Servais et al. (2015) [FR] [41] | Case series | •Pre-U7 (multi-country, multi-centre [NCT01385917]) •ULENAP (FR, multi-centre [NCT00993161]) | NRa | 35 patients with DMD (mean age: 14 years, range: 9–19 years) | NRa | Glucocorticoids (agents NR) | 6 (17%) | •20 mg/day | NR |
| ACI inhibitors (agents NR) | 24 (69%) | NR | NR | ||||||
| Sherlock et al. (2022) [*] [57] | RCT | RCT (multi-country, multi-centre) (NCT02310763) | NRa | 120 patients with DMD (mean age: 9 years, range NR) | NRa | Glucocorticoids (agents NR) | 120 (100%) | NR | ≥6 months |
| Silversides et al. (2003) [CA] [42] | Retrospective cohort study | The Bloorview MacMillan Children’s Center (Toronto, CA) | 1998–2002 | 33 patients with DMD (mean age: 15 years, range: 10–18 years) | Age at onset of symptoms (<5 years of age), male sex, proximal muscle weakness, increased serum creatine kinase levels, and muscle biopsy and/or genetic testing | Glucocorticoids (DFZ) | 21 (64%) | Initial dose •0.9 mg/kg/day At 10 years of age •0.76 (0.19) mg/kg/day At 15 years of age •0.61 (0.20) mg/kg/day At 18 years of age •0.59 (0.15) mg/kg/day | 5.1 (SD: 2.4) years |
| ACE inhibitors (agents NR) | 6 (18%) | NR | NR | ||||||
| Cardiotonic agents (digoxin) | 3 (9%) | NR | NR | ||||||
| Spitali et al. (2020) [*] [43] | Retrospective cohort study | •Undisclosed cohort (multi-country, multi-centre) •The Bio-NMD cohort (multi-country, multi-centre) •CINRG DNHS (prospective cohort study; multi-country, multi-centre [NCT00468832]) | NR | 437 patients with DMD (mean: NR, range: NR) | NRa | Glucocorticoids (agents NR) | NR | NR | ≥1 year |
| Takeuchi et al. (2013) [JP] [44] | Retrospective cohort study | The Remudy database (JP, multi-centre) | 2009–2012 | 553 patients with DMD (mean age: 15 years, range: NR) | Genetic testing | Glucocorticoids (PRED) | 242 (44%) | NR | NR |
| van den Bergen et al. (2014) [NL] [46] | Retrospective cohort study | The Dutch Dystrophinopathy Database (DDD) (NL, multi-centre) | 1961–1974; 1980–2006 | 336 patients with DMD (mean age: 15 years, range: NR) | Male sex, genetic testing and/or muscle biopsy, and loss of ambulation before 13 years of age | Glucocorticoids (agents NR) | 165 (49%) | NR | NR |
| van den Bergen et al. (2014) [NL] [45] | Retrospective cohort study | The Dutch Dystrophinopathy Database (DDD) (NL, multi-centre) | NR | 114 patients with DMD (mean age: NR, range: NR) | Genetic testing | Glucocorticoids (agents NR) | 48 (42%) | NR | NR |
| van den Bergen et al. (2015) [†] [47] | Retrospective cohort study | Neuromuscular databases (multi-country, multi-centre) | NR | 336 patients with DMD (mean age: NR, range: NR) | Muscle biopsy and/or genetic testing | Glucocorticoids (agents NR) | 102 (30%) | NR | NR |
| Vry et al. (2016) [‡] [48] | Retrospective cohort study | The TREAT-NMD global DMD database (multi-national, multi-centre) | 2011–2012 | 1,062 patients with DMD (mean age: 13 years, range: 1–46 years) | Database-specific (see article for details) | Glucocorticoids (agents NR) | 792 (75%)c | NR | NR |
| Wang et al. (2014) [US] [50] | Retrospective cohort study | DuchenneConnect (now the Duchenne Registry) (US, multi-centre) | 2007–2011 | 1,057 patients with DMD (mean age: NR, range: NR) | NR | Glucocorticoids (DFZ and/or PDN) | 633 (60%) | NR | NR |
| Wang et al. (2018) [US] [49] | Retrospective cohort study | DuchenneConnect (now the Duchenne Registry) (US, multi-centre) | NR | 765 patients with DMD (mean age: NR, range: NR) | NR | Glucocorticoids (DFZ and/or PDN) | NR | NR | NR |
| Yılmaz et al. (2004) [TR] [51] | Retrospective cohort study | NR | NR | 88 patients with DMD (mean age: 7 years, range: 3–13 years) | NR | Glucocorticoids (PRED) | 66 (75%) | 0.75 mg/kg/day | 2.75 (1.1) (range: 1.5–5) years |
| Zhang et al. (2021) [CN] [13] | Retrospective cohort study | Neuromuscular centres (see article for details) (CN, multi-centre) part of TREAT-NMD | 2015–2019 | 967 patients with DMD (mean age: NR, range: NR) | Age at onset of symptoms (<5 years of age), elevated serum creatine kinase (CK) levels, and genetic testing | Glucocorticoids (DFZ, PDN, and/or PRED) | 530 (55%) | •DFZ: 0.9 mg/kg/day •PDN/PRED: 0.3–0.75 mg/kg/day | NR |
Note: Canada (CA). China (CN). Deflazacort (DFZ). Duchenne muscular dystrophy (DMD). France (FR). Germany (DE). Italy (IT). Japan (JP). Not applicable (NA). Not reported (NR). Prednisolone (PRED). Prednisone (PDN). Randomized controlled trial (RCT). Serbia (RS). The Netherlands (NL). Turkey (TR). United Kingdom (UK). United States of America (US). *Multi-national (see article for details). †The Netherlands, Italy, France, and the United Kingdom. ‡Bulgaria, the Czech Republic, Denmark, Germany, Hungary, Poland, and the United Kingdom. aDetails not reported but provided in referenced publications. bResults for the Cincinnati Children’s Hospital Medical Center (CCHMC) cohort were not significant. cPast and current use.