Most research and drug development for individuals with Duchenne muscular dystrophy (DMD) overlooks nonambulatory individuals, according to a new study published in Therapeutic Innovation & Regulatory Science.

Patient-focused drug development (PFDD) is an approach to assessing endpoints that prioritize the quality of life improvements for nonambulatory patients with DMD. The researchers conducted a mixed-methods study to understand the unmet needs of these patients and to evaluate the efficacy of the Performance of the Upper Limb Patient-Reported Outcome Measure (PUL-PROM) as an outcome measure.

The investigators enrolled 275 nonambulatory patients from 8 countries with DMD between October 2018 and May 2020, 67% of whom were in the early stages of no ambulation. The patients (n=101) or their caregivers (n=174) answered surveys to provide information on significant symptoms and anticipated benefits of new treatments. They also completed the PUL-PROM to evaluate upper limb functioning, the EuroQol-5 Dimension instrument to assess the quality of life, and a mobility measure to categorize the stage of disease progression relating to ambulatory capabilities.


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Although 4 categories were possible, this study focused solely on the “early nonambulatory” and “late nonambulatory” categories, indicating full-time wheelchair use by all study participants. Three primary thematic areas came to the forefront during data analysis:

  • Muscle functioning, especially upper extremity functioning
  • Body system functioning, especially respiratory, cardiac, and digestive functioning
  • Quality of life, especially the focus on independence, energy levels, and medication side effects

Upper limb functioning correlated significantly with quality of life (r =.42, P ≤.001). Patients in the early stages of no ambulation achieved higher PUL-PROM scores. The mean PUL-PROM score totaled 22 out of 64 points with higher scores reflecting better functioning. Late-stage nonambulatory patients desired medications that improved body system functioning, while early-stage nonambulatory patients prioritized drugs that improved muscle functioning.

“It provides new insights into the burden of Duchenne in non-ambulatory patients overall and by non-ambulatory disease stage,” the authors said. “It also provides insights into ways in which new treatments could alleviate that burden.”

Reference

Schuster ALR, Crossnohere NL, Fischer R, Furlong P, Bridges JFP. Unmet therapeutic needs of non-ambulatory patients with Duchenne muscular dystrophy: a mixed-method analysis. Ther Innov Regul Sci. Published online March 24, 2022. doi:10.1007/s43441-022-00389-x