Evaluation of effects of continued corticosteroid treatment on cardiac and pulmonary function in non-ambulatory males with Duchenne muscular dystrophy from MD STARnet

Abstract

Introduction/aims: Corticosteroids have been shown to improve muscle strength and delay loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD) and are considered standard of care despite significant side-effects. The objective of this study is to evaluate whether corticosteroid treatment after LOA is beneficial for cardiac or pulmonary functions among boys with DMD.

Methods: We used the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to characterize associations between corticosteroid use and onset of abnormal left ventricular (LV) function or abnormal percent predicted forced vital capacity (ppFVC) among 398 non-ambulatory boys with DMD. Kaplan-Meier curve estimation was used to compare time to onset by corticosteroid use groups; Cox proportional hazards modeling was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals.

Results: We found no differences in time to onset of abnormal LV function by corticosteroid use groups. We observed a longer time from LOA to first abnormal ppFVC in boys that were treated with corticosteroid ≥1 y beyond LOA compared with those with no corticosteroid use or those who stopped corticosteroid use within 1 y of LOA.

Discussion: Our findings show no association of corticosteroid use beyond LOA with the onset of abnormal LV function, but a significant association with a delay in onset of abnormal ppFVC. Prospective studies of corticosteroid use in boys with DMD who have lost ambulation may identify benefits and can better elucidate risks, allowing for more effective counseling of patients on continuing treatment after LOA.

Keywords: Duchenne muscular dystrophy; cardiomyopathy; corticosteroid.

Figure 1.

Case selection to identify non-ambulatory boys with DMD, MD STARnet 1982-2012.

Figure 2.. Effect of corticosteroid use beyond LOA on onset of abnormal LV function in non-ambulatory boys with DMD, MD STARnet 1982-2012.

Comparison of corticosteroid exposure in males with DMD not treated with corticosteroid to those stopping corticosteroids within a year of LOA, and those treated for ≥1 year after LOA. A) Observed median age of abnormal LV function. T-tests for pairwise comparisons were not statistically significant. B) Kaplan-Meier curves comparing age at abnormal LV function in the three corticosteroid exposure groups (χ²=1.27, p=0.53). C) Observed median time from LOA to abnormal LV function in the three corticosteroid exposure groups. Observed mean time from LOA to onset of abnormal LV function for those never on corticosteroids and those who discontinued within 1 year of LOA were longer than for those who continued corticosteroids ≥1 year after LOA, t=2.0 (p=0.047) and t=2.09 (p=0.04) respectively. D) Kaplan-Meier curves comparing time from LOA to abnormal LV function in the three corticosteroid exposure groups (χ²= 2.48, p=0.29).

Figure 3.. Effect of corticosteroid use beyond LOA on onset of abnormal pulmonary function in non-ambulatory boys with DMD, MD STARnet 1982-2012.

Comparison of corticosteroid exposure in males with DMD not treated with corticosteroid to those stopping corticosteroids within a year of LOA, and those treated for ≥1 year after LOA. A) Median observed age of first abnormal ppFVC. Mean age at first abnormal ppFVC for those not treated with corticosteroids and those who discontinued within 1 year of LOA were younger than for those who continued corticosteroids ≥1 year after LOA, t= −2.1 (p=0.04) and t= −2.68 (p=0.01) respectively. B) Kaplan-Meier curves comparing age at abnormal ppFVC (χ²=4.03, p=0.13). C) Median time from LOA to abnormal ppFVC. T-tests for pairwise comparisons were not statistically significant. D) Kaplan-Meier curves comparing time from LOA to abnormal ppFVC (χ²= 3.61, p=0.16)