Life Expectancy in Duchenne Muscular Dystrophy: A Systematic Review and Reconstructed Individual Patient Data Meta-Analysis

Background: Duchenne Muscular Dystrophy (DMD) is a rare progressive disease, which is often diagnosed in early childhood, and causes significantly reduced life expectancy. Due to its rarity, research literature and patient numbers are limited. To fully characterise the natural history, appropriate estimates of the life-expectancy of patients with DMD are crucial. Methods: A systematic review of the published literature on mortality in DMD up until July 2020 was undertaken, specifically focusing on publications in which Kaplan-Meier (KM) survival curves with age as a time-scale were presented. These were digitised and individual patient data (IPD) reconstructed. The pooled IPD were analysed using the Kaplan-Meier estimator and parametric survival analysis models. Estimates were also stratified by birth cohort. Findings: Of 1177 articles identified, 14 publications met the inclusion criteria and provided data on 2283 patients, of whom 1049 had died. Median age at death was 22.0 years (95% CI: 21.2, 22.4). Analyses stratifying by three time-periods in which patients were born showed markedly increased life expectancy in more recent patient populations; patients born after 1990 have a median survival of 28.1 years (95% CI 25.1, 30.3). Interpretation: In the absence of large-scale prospective cohort studies or trials reporting mortality data for patients with DMD, extraction of IPD from the literature provides a viable alternative to estimating life-expectancy for this patient population. Further research comparing these estimates to population-level data is warranted in order to assess both possible selection effects and the generalisability of results. Funding: Duchenne UK, NIHR Research Methodology Fellowship. Declaration of Interests: JB and MH received funding from Project HERCULES. MJC and KRA were partially supported by Project HERCULES. Project HERCULES is funded by Duchenne UK, Pfizer, PTC Therapeutics, Roche, Summit Therapeutics PLC, Sarepta Therapeutics Inc, Wave Life Sciences USA Inc, Solid Biosciences, Santhera Pharmaceuticals and Catabasis Pharmaceuticals. JB is supported by a National Institute for Health Research (NIHR) Doctoral Research Fellowship. MC has served as a paid consultant, providing methodological advice, to Roche. MG is (or has been over the past 5 years) the principle investigator for clinical trials sponsored by Pfizer, Italfarmaco, Roche, Summit, Santhera, ReveraGen. She is a member of advisory boards fro NS Pharma and Pfizer (consultancy fees to Newcastle University. She received funding from Sarepta for academic projects through TREAT NMD. KRA has served as a paid consultant to ABPI, AZ, Allergan, Astellas, Amaris, GSK, Janssen, Pfizer, Roche, NICE, Novartis, Congentia, Sanofi, Takeda, NovoNordisk, Abbvie, BMS. KRA is a partner/director of Visible Analytics. KRA has received grants from BHF, HDR UK, MRC and National Institute for Health Research during the course of the study. KRA is a member of the NICE Decision Support Unit (DSU) and the NICE Technical Support Unit (TSU) and has provided strategic and methodological advice to NICE. KRA is a standing member of the NICE Diagnostics Advisory Committee (DAC). KRA is a member of the Health Data Research (HDR) UK/UKRI/SAGE COVID-19 Task Force.