Prognostic factors, disease course, and treatment efficacy in Duchenne muscular dystrophy: A systematic review and meta‐analysis

Abstract

Introduction/Aims Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on prognostic factors that may support treatment decisions. Methods We searched six databases for prospective studies that each included ≥50 DMD patients with a minimum follow‐up of 1 y. Primary outcomes were age at loss of ambulation (LoA), pulmonary function (forced vital capacity percent of predicted, FVC%p), and heart failure. Results Out of 5074 references, 59 studies were analyzed. Corticosteroid use was associated with a delayed LoA (pooled effect hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.23–0.75, I2 94%), better pulmonary function tests (higher peak FVC%, prolonged time with FVC%p > 50%, and reduced need for assisted ventilation) and delayed cardiomyopathy. Longer corticosteroid treatment was associated with later LoA (>1 y compared to <1 y; pooled HR: 0.50, 95% CI 0.27–0.90) and early treatment start (aged <5 y) may be associated with early cardiomyopathy and higher fracture risk. Genotype appeared to be an independent driver of LoA in some studies. Higher baseline physical function tests (e.g., 6‐minute walk test) were associated with delayed LoA. Left ventricular dysfunction and FVC <1 L increased and the use of angiotensin‐converting enzyme (ACE) inhibitors reduced the risk of heart failure and death. Fusion surgery in scoliosis may potentially preserve pulmonary function. Discussion Prognostic factors that may inform clinical decisions include age at corticosteroid treatment initiation and treatment duration, ACE‐inhibitor use, baseline physical function tests, pulmonary function, and cardiac dysfunction.

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 .…”

“…The multivariable, dynamical model of DMD progression described herein has implications both for individualized care of patients with DMD and for clinical trials of new treatments 13,29 . The data suggests that consideration should be given to earlier or more aggressive intervention in Hispanic patients and those with early onset of symptoms.…”

“…Prognostic factors in DMD both predict the disease course and have the potential to individualize patient care and optimize outcomes 13 . Forced vital capacity percent of predicted (FVC%) is a pulmonary function test that is a prognostic factor for DMD outcomes such as loss of ambulation, need for respiratory support, and mortality 13 . Serial FVC% measurements show intra-individual changes with age that are associated with other DMD outcomes 14 .…”

Characteristics of Patients Receiving Novel Muscular Dystrophy Drugs in Trials vs Routine Care

“…Various factors could contribute to nonpersistence, including lack of efficacy, financial challenges, safety concerns related to side effects, and the presence of other health issues . Although our study did not assess the specific reasons for discontinuation, the literature suggests the lack of data on any long-term benefits and cardiac function improvements may be a limitation of exon-skipping treatments, which could be the reason for discontinuation …”

“…8 Although our study did not assess the specific reasons for discontinuation, the literature suggests the lack of data on any long-term benefits and cardiac function improvements may be a limitation of exon-skipping treatments, which could be the reason for discontinuation. 22 , 23 …”