Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis.

Abstract

BackgroundDuchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan diseases, randomized controlled trials are uncommon in DMD, resulting in the need to indirectly compare treatment effects, for example by pooling individual patient-level data from multiple sources. However, to derive reliable estimates, it is necessary to ensure that the samples considered are comparable with respect to factors significantly affecting the clinical progression of the disease. To help inform such analyses, the objective of this study was to review and synthesise published evidence of prognostic indicators of disease progression in DMD. We searched MEDLINE (via Ovid), Embase (via Ovid) and the Cochrane Library (via Wiley) for records published from inception up until April 23 2021, reporting evidence of prognostic indicators of disease progression in DMD. Risk of bias was established with the grading system of the Centre for Evidence-Based Medicine (CEBM).ResultsOur search included 135 studies involving 25,610 patients from 18 countries across six continents (Africa, Asia, Australia, Europe, North America and South America). We identified a total of 23 prognostic indicators of disease progression in DMD, namely age at diagnosis, age at onset of symptoms, ataluren treatment, ATL1102, BMI, cardiac medication, DMD genetic modifiers, DMD mutation type, drisapersen, edasalonexent, eteplirsen, glucocorticoid exposure, height, idebenone, lower limb surgery, orthoses, oxandrolone, spinal surgery, TAS-205, vamorolone, vitlolarsen, ventilation support, and weight. Of these, cardiac medication, DMD genetic modifiers, DMD mutation type, and glucocorticoid exposure were designated core prognostic indicators, each supported by a high level of evidence and significantly affecting a wide range of clinical outcomes.ConclusionThis study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population.