Association of Time of Loss of Ambulation with Severity of Respiratory Symptoms in Patients with Nonsense Mutation Duchenne Muscular Dystrophy (NMDMD)
Author(s)
Tulinius M1, Zhang R2, Lee B3, Madin-Warburton M3, Werner C4, Tomazos I5
1Gothenburg University, Gothenburg, Sweden, 2PTC Therapeutics Sweden AB, Stockholm, AB, Sweden, 3Lumanity, London, UK, 4PTC Therapeutics, Frankfurt/Main, Germany, 5PTC Therapeutics Inc, South Plainfield, NJ, USA
Presentation Documents
OBJECTIVES: Age at loss of ambulation (AALoA) and respiratory symptoms for nmDMD have been compared between patients receiving ataluren from the STRIDE registry and standard of care (SoC) from the CINRG study. A 4-year delay in loss of ambulation (LoA) was demonstrated for ataluren-treated patients. However, estimating treatment effects on respiratory function is challenging due to data limitations. This study aimed to assess the association between LoA and respiratory function - defined by predicted forced vital capacity (pFVC).
METHODS: To determine how pFVC is related to AALoA over time, random-effect regression analysis was performed with AALoA as a covariate on pFVC using LoA data from CINRG. To explore how the decline in pFVC following LoA changes by treatment, time-to-event analysis was performed for patients with LoA to compare time from LoA to pFVC<50% in STRIDE and with a subset of CINRG patients using propensity score matching.
RESULTS: In CINRG, regression analysis demonstrated both a faster rate of decline in pFVC at earlier LoA and a clear dependence between AALoA and pFVC. The expected pFVC is higher for later AALoA, in particular the age when pFVC is 50% is estimated as 9.4 (95%CrI 8.6-10.3) to 19.5 (95%CrI 17.1-21.5) years for AALoA of 5 and 20 respectively. Time to pFVC<50% after LoA was not significantly different between CINRG and STRIDE (HR 1.01 [95%CI, 0.55-1.85]), however the analysis was not sufficiently powered to estimate any additional clinically important improvements.
CONCLUSIONS: The results support that delay in LoA is associated with delayed respiratory decline at any age. Though the time from LoA to pFVC<50% is similar between ataluren and SoC, the time at which patients reach LoA is significantly delayed by ataluren. Together these results infer that delay in LoA due to ataluren will lead to comparable delay in decline of respiratory outcomes.
Conference/Value in Health Info
Value in Health, Volume 26, Issue 6, S2 (June 2023)
Code
RWD59
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Clinical Outcomes Assessment, Prospective Observational Studies, Registries, Relating Intermediate to Long-term Outcomes
Disease
Drugs