Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study

McDonald, Craig M.; Henricson, E.; Abresch, Richard T.; Duong, Tina; Joyce, Nanette C.; Hu, Fengming; Clemens, Paula R.; Hoffman, Eric P.; Cnaan, Avital; Gordish‐Dressman, Heather; Vishwanathan, Vijay; Chidambaranathan, S.; Biggar, W. Douglas; McAdam, Laura; Mah, Jean K.; Tulinius, M.; Morgenroth, Lauren P.; Leshner, Robert T.; Rocha, Carolina Tesi; Thangarajh, Mathula; Kornberg, Andrew J.; Ryan, Monique M.; Nevo, Yoram; Dubrovsky, Alberto; Abdel-Hamid, Hoda; Connolly, Anne M.; Pestronk, Alan; Teasley, Jean; Bertorin, Tulio E.; Webster, Richard; Kolski, Hanna; Kuntz, Nancy L.; Driscoll, Sherilyn W.; Bodensteiner, John B.; Carlo, Jose; Gorni, Ksenija; Lotze, Timothy; Day, John W.; Karachunski, Peter

doi:10.1016/s0140-6736(17)32160-8

Cited by 335 publications

(422 citation statements)

References 23 publications

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“…The finding for LoA in this post hoc analysis is consistent with data from the large (N = 340), observational, Cooperative International Neuromuscular Research Group‐Duchenne Natural History Study (CINRG‐DNHS), in which deflazacort further delayed LoA by nearly 3 years compared with prednisone/prednisolone (daily regimen) and those from a more recently published, long‐term, prospective, cohort study from CINRG (N = 440) that showed further delays of 2.7 years in LoA with deflazacort compared with prednisone/prednisolone …”

Section: Discussionsupporting

confidence: 84%

“…Loss of ambulation constitutes a substantial disability for DMD patients and it marks the beginning of a more severe stage of the disease. Delaying LoA has been correlated with delaying the time to loss of subsequent disease milestones such as decline in respiratory function …”

Section: Discussionmentioning

confidence: 99%

“…Duchenne muscular dystrophy, a rare, irreversible, X‐linked disorder, results in a progressive decline in muscle function and when left untreated, leads to loss of ambulation (LoA) by age 10–12 years and death from cardiac or respiratory failure by the late teens to approximately 25 years of age . The current standard of care for DMD includes corticosteroid therapy with prednisone, prednisolone, or deflazacort, with accumulating evidence suggesting that these agents can slow the decline in muscle strength and motor function, delay LoA, possibly decrease the development of scoliosis requiring operative management, and slow the loss of upper limb function and the rate of pulmonary function decline …”

mentioning

confidence: 99%

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Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial

Shieh¹,

McIntosh

Jin

et al. 2018

Muscle and Nerve

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial

Shieh¹,

McIntosh

Jin

et al. 2018

Muscle and Nerve

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“…D uchenne muscular dystrophy (DMD) is the most common muscular dystrophy in childhood, affecting 1.12 of 10,000 males aged 5–24 years in the United States . Glucocorticoids have been and remain the mainstay of therapy to slow the decline of cardiopulmonary function and muscle strength, thus delaying loss of ambulation and lengthening life expectancy …”

mentioning

confidence: 99%

Use of bone age for evaluating bone density in patients with Duchenne muscular dystrophy: A preliminary report

2019

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Introduction Patients with Duchenne muscular dystrophy (DMD) exhibit low bone mineral density and increased fracture risk. Because glucocorticoid therapy results in delayed puberty and short stature, it is important to account for delayed skeletal development when interpreting patients’ bone mineral density. Methods Twelve glucocorticoid‐treated patients with DMD were evaluated by dual x‐ray absorptiometry scans and wrist x‐rays to estimate bone density and bone age, respectively. Z‐scores were determined on the basis of chronological age. Each patient was assigned a “corrected” birth date that was calculated according to bone age, and a bone‐age‐corrected z‐score was determined. Results Z‐scores adjusted for chronological age were lower than those adjusted for bone age. Discussion We suggest the use of bone age as an alternative to chronological age for analysis of bone mineral density in glucocorticoid‐treated patients with DMD. Additional research is required to determine the optimal method to predict fracture risk in this patient group. Muscle Nerve 59:422–425, 2019

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“…Fortunately, natural history studies are facilitating a definition of predictive clinical end points and biomarker development. Studies of hundreds of patients in international collaborative studies aim to identify early sensitive and reliable outcome measures that are predictive of later quality of life changes — these are then strong PD end points …”

Section: Extrapolation Of Clinical Outcomes As Pd End Pointsmentioning

confidence: 99%

Developmental Pharmacodynamics and Modeling in Pediatric Drug Development

Conklin

Hoffman

Anker

2019

The Journal of Clinical Pharma

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Challenges in pediatric drug development include small patient numbers, limited outcomes research, ethical barriers, and sparse biosamples. Increasingly, pediatric drug development is focusing on extrapolation: leveraging knowledge about adult disease and drug responses to inform projections of drug and clinical trial performance in pediatric subpopulations. Pharmacokinetic‐pharmacodynamic (PK‐PD) modeling and extrapolation aim to reduce the numbers of patients and data points needed to establish efficacy. Planning for PK‐PD and biomarker studies should begin early in the adult drug development program. Extrapolation relies on the assumption that both the underlying disease and the mechanism of action of the drug used to treat that disease are similar in adults and pediatric subpopulations. Clearly, developmental changes in PK and PD need to be considered to enhance the quality of PK‐PD modeling and, therefore, increase the success of extrapolation. This article focuses on the influence of differences in PD between adults and pediatric subpopulations that are highly relevant for the use of extrapolation.

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Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study

Cited by 335 publications

References 23 publications

Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial

Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial

Use of bone age for evaluating bone density in patients with Duchenne muscular dystrophy: A preliminary report

Developmental Pharmacodynamics and Modeling in Pediatric Drug Development

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