Functional and Clinical Outcomes Associated with Steroid Treatment among Non-ambulatory Patients with Duchenne Muscular Dystrophy

Abstract

Background: Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited. Objective: Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD. Methods: Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models. Results: This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p < 0.05). Both steroids were associated with significantly slower average declines in LVEF, improvement in CPF, and slower declines in total PUL score and EK total score vs. no steroids; deflazacort was associated with slower declines in total PUL score vs. prednisone (all p < 0.05). Both steroids also preserved functional abilities considered especially important to quality of life, including the abilities to perform hand-to-mouth function and to turn in bed at night unaided (all p < 0.05 vs. no steroids). Conclusions: Steroid use after loss of ambulation in DMD was associated with delayed progression of important pulmonary, cardiac, and upper extremity functional deficits, suggesting some benefits of deflazacort over prednisone.

Mathematical modeling of the progression of Duchenne Muscular Dystrophy in San Diego in an era of allele specific oligonucleotide therapy

“…The factor that contributed most to the model size was steroid therapy, which delayed FVC% decline, and had maximal effect when started at less than 10 years of age. As noted above, this was not surprising, albeit the relative magnitude of the bene t in young versus old boys was larger than previously reported 13,[19][20][21][22][23]28 .…”

“…Eteplirsen, de azacort, golodirsen, and casimersen, and delandistrogene moxeparvovec-rokl were approved by the FDA in 2016, 2017, 2019, 2021, and 2023, respectively. De azacort is a synthetic steroid that has greater bene t than prednisone in DMD patients [21][22][23] . Eteplirsen, golodirsen, and casimersen are phosphorodiamidate morpholino ASOs designed to cause skipping of exons 51, 53, and 45, respectively, in the dystrophin gene that lead to translation of a truncated but functional dystrophin protein 10 .…”

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids

“…Individuals on DFZ were associated with better performance in the EK scale domains assessing transfer, wheelchair balance and hand‐to‐mouth function, but without differences in the time to lose the last two late‐stage milestones compared to individuals on PDN. Similar to us, the PRO‐DMD‐01 study did not report differences in the rate of decline or in the time to late stage respiratory, cardiac and hand‐to‐mouth function milestones between PDN and DFZ; however, individuals on DFZ showed a lesser decline in the performance of the upper limb scale [36]. Given that both studies are observational and non‐randomized, it remains challenging to ascertain whether the positive impact of DFZ on the EK scale functional abilities and the performance of the upper limbs is influenced by the high prevalence of DFZ use amongst individuals or if it genuinely reflects a more favourable effect on late‐stage motor functions.…”

Comparison of pharmaceutical properties and biological activities of prednisolone, deflazacort, and vamorolone in DMD disease models

“…Evidence from randomized clinical trials indicated that corticosteroids improve muscle function in DMD, delaying the time to loss of ambulation relative to no treatment with corticosteroids [ 14 ]. In subsequent studies, corticosteroid use in non-ambulatory patients with DMD was associated with delayed progression of pulmonary, cardiac, and upper limb loss of function when compared with those who did not receive corticosteroids [ 15 ]. Deflazacort is administered as a prodrug that forms the active metabolite 21-des deflazacort in plasma.…”