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Research Article
23 August 2023

Real-world evidence of eteplirsen treatment effects in patients with Duchenne muscular dystrophy in the USA

Authors: Joel Iff https://orcid.org/0000-0002-1102-0651, Yi Zhong https://orcid.org/0000-0001-6246-2292 [email protected], Edward Tuttle, Deepshekhar Gupta, Xander Paul, and Erik Henricson https://orcid.org/0000-0002-7511-6441Author Info & Affiliations
Volume 12, Number 9
https://doi.org/10.57264/cer-2023-0086
PDFFormats

Abstract

Aim: To evaluate treatment effects of eteplirsen among patients with Duchenne muscular dystrophy. Methods: Using real-world claims and electronic medical record data, this retrospective comparative analysis assessed eteplirsen-treated and control cohorts matched by age, disease progression state, and pre-index period healthcare resource utilization. Poisson regression was used to evaluate eteplirsen effects on healthcare resource utilization outcomes. Results: Eteplirsen was associated with statistically significant reductions in rates of hospital encounters (31%), emergency room visits (31%), need for pulmonary management (33%), cardiac management (21%), tracheostomy (86%), and assisted ventilation (39%) versus the control group. Other assessed outcomes favored eteplirsen numerically but did not all reach statistical significance. Conclusion: Eteplirsen-treated patients had reduced rates of multiple healthcare resource utilization measures versus matched controls.

Plain language summary

How eteplirsen treatment impacts the health of people living with Duchenne muscular dystrophy in the United States

What is this article about?

Duchenne muscular dystrophy (DMD) is a rare genetic disease. People with DMD do not make a protein called dystrophin. This leads to damage to all muscles, including the heart and the muscles used for breathing. Patients also lose the ability to walk and take care of themselves. Treatment for DMD is complex, and as the disease progresses, patients use more healthcare resources. Eteplirsen is a treatment for people with DMD, which is caused by mutations in a specific part of the gene, and helps produce shortened but functional dystrophin. Researchers looked at information from insurance claims and electronic medical records to compare healthcare resource use in people who received eteplirsen (n = 579) and those who received standard of care (n = 1296).

What were the results?

Patients receiving eteplirsen had significantly fewer hospital admissions (31%) and emergency room visits (31%). Patients also had a reduced need for special care of the lungs (pulmonary management) (33%), care for the heart (cardiac management) (21%), special surgery to access the windpipe (tracheostomies) (86%), and help with breathing (assisted ventilation) (39%) compared with patients who received standard of care.

What do the results mean?

These results suggest that people who received eteplirsen in routine clinical care settings used healthcare resources less often compared with patients who did not receive eteplirsen. Similar findings were seen in people receiving eteplirsen in clinical trials. These results suggest that eteplirsen treatment delays muscle damage in people with DMD.

Supplementary Material

File (supplemnetary data.docx)

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat. Rev. Dis. Primers 7(1), 13 (2021).
PubMed
Google Scholar
2.
Brooke MH, Fenichel GM, Griggs RC et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology 39(4), 475–481 (1989).
PubMed
Google Scholar
3.
McDonald CM, Abresch RT, Carter GT et al. Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am. J. Phys. Med. Rehabil. 74(Suppl. 5), S70–S92 (1995).
PubMed
Google Scholar
4.
Sheehan DW, Birnkrant DJ, Benditt JO et al. Respiratory management of the patient with Duchenne muscular dystrophy. Pediatrics 142(Suppl. 2), S62–S71 (2018).
PubMed
Google Scholar
5.
Bushby K, Finkel R, Birnkrant DJ et al. The D. M. D. Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 9(2), 177–189 (2010).
PubMed
Google Scholar
6.
Ouyang L, Grosse SD, Kenneson A. Health care utilization and expenditures for children and young adults with muscular dystrophy in a privately insured population. J. Child Neurol. 23(8), 883–888 (2008).
PubMed
Google Scholar
7.
Thayer S, Bell C, McDonald CM. The direct cost of managing a rare disease: assessing medical and pharmacy costs associated with Duchenne muscular dystrophy in the United States. J. Manag. Care Spec. Pharm. 23(6), 633–641 (2017).
PubMed
Google Scholar
8.
Broomfield J, Hill M, Guglieri M, Crowther M, Abrams K. Life expectancy in Duchenne muscular dystrophy: reproduced individual patient data meta-analysis. Neurology 97(23), e2304–e2314 (2021).
PubMed
Google Scholar
9.
Eagle M, Baudouin SV, Chandler C et al. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul. Disord. 12(10), 926–929 (2002).
PubMed
Google Scholar
10.
Landfeldt E, Edström J, Buccella F, Kirschner J, Lochmüller H. Duchenne muscular dystrophy and caregiver burden: a systematic review. Dev. Med. Child Neurol. 60(10), 987–996 (2018).
PubMed
Google Scholar
11.
Manzur AY, Kinali M, Muntoni F. Update on the management of Duchenne muscular dystrophy. Arch. Dis. Child. 93(11), 986–990 (2008).
PubMed
Google Scholar
12.
Centers for Disease Control and Prevention. Duchenne muscular dystrophy care considerations. https://www.cdc.gov/ncbddd/musculardystrophy/care-considerations.html (2022).
Google Scholar
13.
Ryder S, Leadley RM, Armstrong N et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J. Rare Dis. 12(1), 79 (2017).
PubMed
Google Scholar
14.
Grootenhuis MA, de Boone J, van der Kooi AJ. Living with muscular dystrophy: health related quality of life consequences for children and adults. Health Qual. Life Outcomes 5, 31 (2007).
PubMed
Google Scholar
15.
Szabo SM, Audhya IF, Malone DC, Feeny D, Gooch KL. Characterizing health state utilities associated with Duchenne muscular dystrophy: a systematic review. Qual. Life Res. 29(3), 593–605 (2020).
PubMed
Google Scholar
16.
McDonald CM, Henricson EK, Abresch RT et al. The CINRG Investigators. The cooperative international neuromuscular research group Duchenne natural history study--a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used. Muscle Nerve 48(1), 32–54 (2013).
PubMed
Google Scholar
17.
Guiraud S, Chen H, Burns DT, Davies KE. Advances in genetic therapeutic strategies for Duchenne muscular dystrophy. Exp. Physiol. 100(12), 1458–1467 (2015).
PubMed
Google Scholar
18.
Messina S, Vita GL. Clinical management of Duchenne muscular dystrophy: the state of the art. Neurol. Sci. 39(11), 1837–1845 (2018).
PubMed
Google Scholar
19.
Servais L, Mercuri E, Straub V et al; and the SKIP-NMD Study Group. Long-term safety and efficacy data of golodirsen in ambulatory patients with Duchenne muscular dystrophy amenable to exon 53 skipping: a first-in-human, multicenter, two-part, open-label, phase 1/2 trial. Nucleic Acid Ther. 32(1), 29–39 (2022).
PubMed
Google Scholar
20.
Khan N, Eliopoulos H, Han L et al; and the Eteplirsen Investigators and the CINRG DNHS Investigators. Eteplirsen treatment attenuates respiratory decline in ambulatory and non-ambulatory patients with Duchenne muscular dystrophy. J. Neuromuscul. Dis. 6(2), 213–225 (2019).
PubMed
Google Scholar
•• This study reports clinically meaningful attenuation of percent predicted forced vital capacity decline after eteplirsen compared with natural history data.
21.
Kinali M, Main M, Eliahoo J et al. Predictive factors for the development of scoliosis in Duchenne muscular dystrophy. Eur. J. Paediatr. Neurol. 11(3), 160–166 (2007).
PubMed
Google Scholar
22.
Mendell JR, Goemans N, Lowes LP et al; and the Eteplirsen Study Group and the Telethon Foundation D. M. D. Italian Network. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann. Neurol. 79(2), 257–271 (2016).
PubMed
Google Scholar
•• This study demonstrates a slower rate of decline in ambulation among patients treated with eteplirsen compared with natural history data.
23.
Mendell JR, Khan N, Sha N et al; and the Eteplirsen Study Group. Comparison of long-term ambulatory function in patients with Duchenne muscular dystrophy treated with eteplirsen and matched natural history controls. J. Neuromuscul. Dis. 8(4), 469–479 (2021).
PubMed
Google Scholar
•• This long-term study reports attenuation of ambulatory decline over 4 years among eteplirsen-treated patients compared with natural history data.
25.
Harris L, L'Italien G, Kumar A et al. Real-world assessment of the relationship between migraine-related disability and healthcare costs in the United States. Headache 62(4), 473–481 (2022).
PubMed
Google Scholar
26.
LaVallee C, Bansal I, Kamdar S, Kwong WJ, Boccia RV. Relationship between initial parenteral iron therapy dosing and treatment effectiveness: a real-world retrospective analysis. J. Blood Med. 13, 133–142 (2022).
PubMed
Google Scholar
27.
Wang SV, Pinheiro S, Hua W et al. STaRT-RWE: structured template for planning and reporting on the implementation of real world evidence studies. BMJ 372, (2021).
Crossref
Google Scholar
• This template serves as a guiding tool for designing and conducting reproducible real-world evidence studies.
28.
U.S. Department of Health and Human Services. Real-world data: assessing electronic health records and medical claims data to support regulatory decision making for drug and biological products, guidance for industry. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Oncology Center of Excellence (OCE), 1–39 (2021).
Google Scholar
• This FDA guidance provides a framework for the inclusion of electronic health records or medical claims data in clinical studies.
29.
Iff J, Zhong Y, Gupta D et al. The CINRG DNHS Investigators. Disease progression stages and burden in patients with Duchenne muscular dystrophy using administrative claims supplemented by electronic medical records. Adv. Ther. 39(6), 2906–2919 (2022).
PubMed
Google Scholar
•• This study provides an algorithm for stage classification of patients with DMD and suggests that large-scale claims data supplemented by EMR may inform the design of future real-world studies.
30.
Landfeldt E, Lindgren P, Bell CF et al. The burden of Duchenne muscular dystrophy: an international, cross-sectional study. Neurology. 83(6), 529–536 (2014).
PubMed
Google Scholar
31.
Wang RT, Barthelemy F, Martin AS et al. DMD genotype correlations from the Duchenne Registry: endogenous exon skipping is a factor in prolonged ambulation for individuals with a defined mutation subtype. Hum. Mutat. 39(9), 1193–1202 (2018).
PubMed
Google Scholar
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