(257) Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Literature Review

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 588

Presenting Author(s)

Anne Broe, MD, PhD
– Epidemiologist, IQVIA (UK), London, United Kingdom

Co-Author(s)

Katharina Buesch
– PTC Therapeuticsw, Steinhausen/Zug, Zug, Switzerland
Nermina Ferizovic
– PTC Therapeuticsw, Steinhausen/Zug, Zug, Switzerland
Erik Landfeldt
– ICON plc, Sweden

Background: Duchenne muscular dystrophy (DMD) is a rare, chronic, and fatal disease caused by a dystrophin mutation resulting in progressive muscle weakening. A critical milestone of DMD is loss of ambulation (LoA), which has been shown to be significantly associated with the risk and severity of subsequent disease complications, patient quality of life, caregiver burden, and costs.

Objectives: The objective of our study was to review the literature for evidence of predictors of LoA in patients with DMD.

Methods: We searched MEDLINE, Embase and the Cochrane Library for records of studies published from inception up until May 31, 2021, reporting evidence of predictors of LoA in patients with DMD. Levels of evidence were established with the grading system of the Centre for Evidence-Based Medicine (CEBM), ranging from level 1 (indicating high quality) to level 4 (indicating poor quality).

Results: The search resulted in the inclusion of 33 studies involving 13,233 patients with DMD. We identified two predictors associated with younger age at LoA: age at diagnosis (one study, distribution across CEBM evidence levels [level 1-level 5]: 0%, 0%, 0%, 0%, 100%); and age at onset of symptoms (one study: 0%, 100%, 0%, 0%, 0%). We identified four predictors associated with older age at LoA: height/weight (one study: 0%, 0%, 0%, 100%, 0%); eteplirsen treatment (one study: 0%, 100%, 0%, 0%, 0%); ataluren treatment (three studies: 0%, 33%, 66%, 0%, 0%); and glucocorticoid exposure (23 studies: 0%, 26%, 8.7%, 61%, 4.3%). Finally, we identified two predictors associated with younger/older age at LoA: DMD genetic modifiers (three studies: 0%, 66%, 0%, 33%, 0%); and DMD mutation types (seven studies: 0%, 14.3%, 0%, 85.7%, 0%).

Conclusions: Our study provides an up-to-date summary of predictors of LoA in DMD, which helps inform the design of future research and data collection initiatives in this patient population.