Long-Term Data Shows Trade-off Between Daily, Intermittent Corticosteroids in Patients With Duchenne

Findings newly published in the Journal of Neurology, Neurosurgery & Psychiatry indicated that the long-standing clinical trade-off between daily and intermittent corticosteroid (CS) regimens in Duchenne muscular dystrophy (DMD) become more pronounced the longer patients were followed.¹

These findings potentially reinforce the need for individualized, longitudinal shared decision-making rather than a one-size-fits-all approach to steroid dosing. The study, led by pediatric neurologist Nadine A. Ikelaar, MD, who is also a PhD student at Leiden University Medical Center, compared outcomes in patients treated with daily deflazacort against those on a 10-days-on/10-days-off intermittent regimen using prednisone or deflazacort, with mean follow-up approaching a decade in both groups.

Study Overview

Investigators retrospectively analyzed data from 219 individuals with DMD treated at 3 neuromuscular referral centers in Belgium and the Netherlands between January 1995 and June 2022. Of these, 75 patients received daily deflazacort (primarily from the Belgian site) and 144 received intermittent CS, either prednisone or a switch from prednisone to deflazacort (primarily from the 2 Dutch sites).

Median age at CS initiation was similar between groups (5.6 vs 5.5 years), as was mean follow-up (10.7 vs 9.5 years). Outcomes spanned motor function, pulmonary and cardiac function, anthropometrics, and bone health, and were analyzed using linear mixed-effects models, beta regression, and Kaplan-Meier survival analysis.

Key Findings

Overall, patients on daily CS lost ambulation later than those on intermittent CS (median age 15.0 vs 11.0 years; P <.001) and showed significantly slower decline across all motor measures, including North Star Ambulatory Assessment, 10-meter run velocity, 6-minute walk test, and Performance of the Upper Limb 2.0 (P ≤.015 for all). By age 18, only 5.5% of patients on daily CS had lost hand-to-mouth function, compared with 37.5% on intermittent CS. Daily-treated patients also underwent spinal fusion surgery less often (16.0% vs 27.1%; P <.05), albeit at an older age.

READ MORE: FDA Extends Deramiocel Review for Duchenne Muscular Dystrophy After HOPE-3 Amendment

The advantages reversed for growth and skeletal outcomes. At age 18, patients on intermittent CS were markedly taller (170.2 cm vs 140.8 cm; P <.001) and had higher predicted bone mineral density (BMD) Z-scores (−2.9 vs −4.9; P <.001). Fractures occurred in 74.7% of patients on daily CS versus 36.8% on intermittent CS (P <.001), with vertebral fractures disproportionately driving this difference (48.0% vs 12.5%). Body mass index, annual cardiac fractional shortening decline, and age at forced vital capacity below 60% of predicted did not differ significantly between regimens.

Clinical Context and Interpretation

CS therapy is standard of care in DMD, initiated around age 4 to 5 years to slow muscle weakness progression, but its benefits must be balanced against well-documented adverse effects, including growth suppression, reduced BMD, weight gain, and behavioral changes.² Prior studies established that daily regimens outperform intermittent dosing for ambulatory motor outcomes, but most prior data were limited to the ambulatory phase and shorter follow-up windows.³ Randomized trials such as FOR-DMD have compared dosing schedules but with more constrained follow-up duration.⁴

The authors emphasized that differences between regimens widened over time, particularly for height and BMD, which had not plateaued by the end of follow-up. This suggests that risk-benefit assessments based on trial-length data may understate the eventual divergence between regimens. The persistence of motor benefit into the non-ambulatory phase, reflected in preserved upper-limb and hand-to-mouth function, extends the clinical case for daily CS beyond ambulation alone, while the markedly higher fracture burden argues for proactive bone health monitoring in daily-treated patients.

Limitations and Future Research

The retrospective design introduced site-level heterogeneity, including different vertebral fracture screening protocols (routine imaging at 2 sites vs indication-based imaging at the third), likely underestimating fracture incidence in some patients. No patients received daily prednisone, precluding a direct steroid-type comparison independent of regimen. Data on other recognized CS adverse effects, such as cataracts, delayed puberty, glucose intolerance, and behavioral change, were not consistently available in medical records.

The authors pointed to vamorolone (Agarmee; Santhera Pharmaceuticals), a dissociative steroid shown in trials to offer motor benefits comparable to daily CS with a potentially more favorable growth and bone safety profile, as a therapy that could reshape this risk-benefit calculus if long-term efficacy is confirmed.⁵ They also called for continued longitudinal data collection beyond the second decade of life, particularly for BMD trajectories, as patients with DMD live longer with chronic CS exposure.

REFERENCES
1. Ikelaar NA, Stoop MHP, van der Holst M, et al. Balancing Benefits and Risks: Long-term Use of Daily versus Intermittent Corticosteroids in Duchenne Muscular Dystrophy. J Neurol Neurosurg Psychiatry. Published online August 24, 2026. doi:10.1136/jnnp-2026-3390712.
2. Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016;2016(5):CD003725. Published 2016 May 5. doi:10.1002/14651858.CD003725.pub4
3. Ricotti V, Ridout DA, Scott E, et al. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry. 2013;84(6):698-705. doi:10.1136/jnnp-2012-303902
4. Guglieri M, Bushby K, McDermott MP, et al. Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA. 2022;327(15):1456-1468. doi:10.1001/jama.2022.4315
5. Clemens PR, Berglund A, Schiava M, et al. Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial. Neurology. 2026;107(1):e214756. doi:10.1212/WNL.0000000000214756