Open access

Research Article

15 August 2019

Ataluren use in patients with nonsense mutation Duchenne muscular dystrophy: patient demographics and characteristics from the STRIDE Registry

Authors: Francesco Muntoni [email protected], Isabelle Desguerre, Michela Guglieri, Andrés Nascimento Osorio, Janbernd Kirschner, Már Tulinius, Filippo Buccella, … Show All … , Gary Elfring, Christian Werner, Traci Schilling, Panayiota Trifillis, Olivia Zhang, Abdallah Delage, Claudio L Santos, and Eugenio MercuriAuthor Info & Affiliations

Publication: Journal of Comparative Effectiveness Research

Volume 8, Number 14

https://doi.org/10.2217/cer-2019-0086

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Abstract

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (DMD) in clinical practice (NCT02369731). Here, we describe the initial demographic characteristics of the registry population. Patients & methods: Patients will be followed up from enrollment for ≥5 years or until study withdrawal. Results & conclusion: As of 9 July 2018, 213 DMD boys were enrolled from 11 countries. Mean (standard deviation) ages at first symptoms and at study treatment start were 2.7 (1.7) years and 9.8 (3.7) years, respectively. Corticosteroids were used by 190 patients (89.2%) before data cut-off. Mean (standard deviation) ataluren exposure was 639.0 (362.9) days. Six patients withdrew. STRIDE is the first drug registry for patients with DMD and represents the largest real-world registry of patients with nmDMD to date.

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References

Papers of special note have been highlighted as: • of interest; •• of considerable interest

1.

Ellis JA, Vroom E, Muntoni F. 195th ENMC International Workshop: newborn screening for Duchenne muscular dystrophy December 14–16, 2012, Naarden, The Netherlands. Neuromuscul. Disord. 23(8), 682–689 (2013).

2.

Bushby K, Finkel R, Birnkrant DJ et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9(1), 77–93 (2010).

3.

Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 17, 251–267 (2018).

• One article in a three-part overview of the 2018 standard of care guidelines for the management of patients with Duchenne muscular dystrophy (DMD).

4.

Pichavant C, Aartsma-Rus A, Clemens PR et al. Current status of pharmaceutical and genetic therapeutic approaches to treat DMD. Mol. Ther. 19(5), 830–840 (2011).

5.

Bladen CL, Salgado D, Monges S et al. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum. Mutat. 36(4), 395–402 (2015).

6.

Laing NG, Davis MR, Bayley K, Fletcher S, Wilton SD. Molecular diagnosis of duchenne muscular dystrophy: past, present and future in relation to implementing therapies. Clin. Biochem. Rev. 32(3), 129–134 (2011).

7.

Bello L, Pegoraro E. Genetic diagnosis as a tool for personalized treatment of Duchenne muscular dystrophy. Acta. Myol. 35(3), 122–127 (2016).

8.

European Medicines Agency. Translarna™ (ataluren) summary of product characteristics (2018). www.ema.europa.eu/documents/product-information/translarna-epar-product-information_en.pdf

9.

Peltz SW, Morsy M, Welch EM, Jacobson A. Ataluren as an agent for therapeutic nonsense suppression. Annu. Rev. Med. 64, 407–425 (2013).

10.

Roy B, Friesen WJ, Tomizawa Y et al. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression. Proc. Natl Acad. Sci. USA 113(44), 12508–12513 (2016).

11.

Bushby K, Finkel R, Wong B et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve 50(4), 477–487 (2014).

•• Describes the safety and efficacy results of ataluren in a Phase IIb randomized, double-blind, placebo-controlled trial.

12.

Mcdonald CM, Campbell C, Torricelli RE et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, Phase III trial. Lancet 390(10101), 1489–1498 (2017).

•• Describes the safety and efficacy results of ataluren in a Phase III randomized, double-blind, placebo-controlled trial.

13.

European Medicines Agency. Summary of the risk management plan (RMP) for Translarna (ataluren) (2014). www.ema.europa.eu/en/documents/rmp-summary/translarna-epar-risk-management-plan-summary_en.pdf

14.

Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 17, 347–361 (2018).

• One article in a three-part overview of the 2018 standard of care guidelines for the management of patients with DMD.

15.

Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol. 17, 445–455 (2018).

• One article in a three-part overview of the 2018 standard of care guidelines for the management of patients with DMD.

16.

Mazzone ES, Messina S, Vasco G et al. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscul. Disord. 19(7), 458–461 (2009).

17.

Mayhew A, Mazzone ES, Eagle M et al. Development of the Performance of the Upper Limb module for Duchenne muscular dystrophy. Dev. Med. Child Neurol. 55(11), 1038–1045 (2013).

18.

Vry J, Gramsch K, Rodger S et al. European cross-sectional survey of current care practices for Duchenne muscular dystrophy reveals regional and age-dependent differences. J. Neuromuscul. Dis. 3(4), 517–527 (2016).

•• Describes patient demographic results from the CARE-NMD project, which evaluated the care practices for 1062 patients with DMD in seven European countries using a cross-sectional survey of patients.

19.

D'Amico A, Catteruccia M, Baranello G et al. Diagnosis of Duchenne muscular dystrophy in Italy in the last decade: critical issues and areas for improvements. Neuromuscul. Disord. 27(5), 447–451 (2017).

•• Describes patient demographic results from a retrospective study investigating the age at diagnosis of DMD in Italy.

20.

Aartsma-Rus A, Ginjaar IB, Bushby K. The importance of genetic diagnosis for Duchenne muscular dystrophy. J. Med. Genet. 53(3), 145–151 (2016).

21.

Fernandez-Marmiesse A, Gouveia S, Couce ML. NGS technologies as a turning point in rare disease research, diagnosis and treatment. Curr. Med. Chem. 25(3), 404–432 (2018).

22.

Martins AM, Kyosen SO. The importance of patient registries for rare diseases. Expert Opin. Orphan Drugs 1(10), 769–772 (2013).

• Describes the heterogeneity of rare diseases and the importance of gathering information in registries about patients with rare diseases.

23.

Collaborative Trajectory Analysis Project. Enabling the right trial design, the first time (2016). http://ctap-duchenne.org/assets/files/cTAP-Overview_2016.pdf

24.

Mcdonald CM, Henricson EK, Abresch RT et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet 391(10119), 451–461 (2018).

25.

Mcdonald CM, Henricson EK, Abresch RT et al. 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).

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