Standard Criteria for Loss of Ambulation Needed in DMD

Multiple definitions of ambulation are used by stakeholders in Duchenne muscular dystrophy (DMD) treatment, but standard criteria are needed to make sure patients eligible for certain treatments can access them, according to a study presented at the Academy of Managed Care Pharmacy 2024 annual meeting.

In DMD, loss of ambulation (LOA) is a critical motor function milestone, but there are several ways that LOA can be defined. Patients or caregivers may report continuous wheelchair use, and clinicians have a range of functional tests at their disposal, including the 10-meter walk/run (10MWR) and the 6-minute walk test (6MWT). While some measures of ambulatory function used in clinical research are useful for treatment efficacy evaluations, they may not be practical in clinical settings.

Person in wheelchair | Image credit: LIGHTFIELD STUDIOS - stock.adobe.com

“Therefore, different definitions of ambulation are used by stakeholders across a variety of settings,” the authors wrote. “Payers often restrict access to approved therapies based on ambulatory status, making it important to evaluate if discrepancies in defining ambulation impact patient access to treatment.”

Study objectives were to assess the agreement and accuracy between 10MWR and 6MWT thresholds and the Cooperative International Neuromuscular Research Group (CINRG) ambulatory definition, which is full-time wheelchair use. Researchers also evaluated 6MWT accuracy compared with the 10MWR test, as well as the time gap between patients’ first 10MWR and 6MWT results and initial report of LOA as defined by the CINRG.

The observational, cross-sectional study included a total of 121 patients aged 7 years of age or older who were enrolled in the CINRG registry from 2006 to 2016 were included in the cohort. The median patient age was 9.3 years, and all patients had 10MWR and 6MWT results available.

According to the CINRG definition, 90.1% of patients in the study were ambulant, with a mean LOA at age 10.3 years. The 10MWR with a threshold of 30 seconds demonstrated strong agreement with the CINRG definition (k = 0.80) and accurately identified 95% of the patients considered ambulant by the CINRG definition. However, the 6MWT with a threshold of 300 meters had weak agreement (k = 0.30) and lower sensitivity (68%) compared with the CINRG definition.

Compared with the 10MWR test, the 6MWT identified 71% of the same patients who retained ambulation, but this means that up to about one-third of ambulant patients may be incorrectly categorized as nonambulant with the 6MWT. However, in an exploratory analysis, the researchers found the 6MWT at thresholds of 180 meters, 200 meters, 250 meters, and 300 meters were able to classify more than half of patients as nonambulant at least 2 years before the CINRG criteria.

The findings suggest that the differences between ambulation definitions for patients with DMD can impact the identification of ambulant vs nonambulant individuals.

“This study provides real-world evidence on the impact of using various definitions and thresholds to identify ambulatory patients with DMD and highlights the need for standard criteria to ensure all patients who may benefit from therapy have access,” the authors concluded.

Reference

Macedo A, Logan J, Dai D, Ricchetti-Masterson K. Agreement and accuracy of ambulatory definitions in Duchenne muscular dystrophy (DMD): A cross-sectional analysis using the Cooperative International Neuromuscular Research Group (CINRG) registry. Abstract presented at: Academy of Managed Care Pharmacy 2024; April 15-18, 2024; New Orleans, LA. Abstract M14.