A Validated Prognostic Score for Time to Loss of Ambulation in Patients With Duchenne Muscular Dystrophy.

BACKGROUND AND

OBJECTIVES

Development of a prognostic score for time to loss of ambulation (LoA) may help guide treatment of patients with Duchenne muscular dystrophy (DMD). Information from clinical data sources was used to create a prognostic score for LoA for use in practice.

METHODS

Data used included 4 natural history databases and 3 clinical trial placebo arms. Inclusion criteria were as follows: (1) 6-minute walk distance ≥75 m; (2) a subsequent visit with an outcome assessment that identified LoA; (3) current corticosteroid use; and (4) available data on prognostic factors. Classification and regression tree models for time to LoA were used to classify patients into 5 risk groups (group 5 = highest risk), prioritizing the easily obtained rise from floor (RFF) and 10-m walk/run (10MWR) times as predictors. The prognostic score was validated in the Cooperative International Neuromuscular Research Group data.

RESULTS

Data from 608 boys were analyzed (mean age 9.1 years). Kaplan-Meier curves for time to LoA for each risk group were well separated, describing meaningful differences in time to LoA. Median time to LoA for risk group 1 was not reached during a median of 2.0 years of follow-up. Median times to LoA for risk groups 2-5 were 4.4 (95% CI 4.0-inf), 3.0 (2.1-4.1), 2.0 (1.6-2.1), and 0.9 (0.8-1.6) years, respectively. These risk groups showed concordant times to LoA among 226 patients in the validation data and provided finer separation of patients across different levels of LoA risk than thresholds based on individual functional tests.

DISCUSSION: Patients with DMD were classified into 5 risk groups for LoA using a simple, easy-to-use prognostic score based on RFF and 10MWR thresholds. The prognostic score replicated well in validation data and performed better than previously proposed classifications used in practice. Incorporating the prognostic score for time to LoA into a clinical visit may allow clinicians to counsel patients on trial eligibility, need for mobility devices, home adjustments, financial accommodations, and psychosocial needs. The prognostic score may also be used in trials to inform inclusion criteria and stratification. Study limitations included limited data for prediction of LoA risk beyond 4 years.