Presentation (CTI)

OBJECTIVES: Degenerative diseases cause irreversible impairment, with treatments aiming to slow progression. Patient reported outcomes (PROs) may not capture the benefit of these treatments. This study examines the relationship between clinical outcomes and PROs in degenerative diseases, focusing on patient perceptions of treatments that slow progression.
METHODS: The pivotal trials of recent Food and Drug Administration (FDA)-approved treatments for degenerative diseases were analyzed; these included nintedanib for idiopathic pulmonary fibrosis (IPF), tofersen for amyotrophic lateral sclerosis (ALS), ocrelizumab for primary-progressive multiple sclerosis (PPMS), and donanemab-azbt for Alzheimer’s disease (AD). For each condition, we evaluated the reported clinical outcomes and corresponding PROs, with a focus on whether PROs aligned with the observed clinical benefits in slowing disease progression.
RESULTS: All 4 drugs were approved based on statistically significant differences vs controls in primary clinical endpoints of disease progression in pivotal trials. Despite these statistical differences, treatment and control groups for all 4 drugs showed decline from baseline in disease progression. In these 4 pivotal trials, treatment benefit in PROs was observed only with tofersen for ALS using the EuroQol-5 Dimension (EQ-5D) scale; although treatment and control groups both experienced declines in EQ-5D scores compared to baseline. No statistically significant differences were observed for other generic and disease-specific PROs across the 4 trials. However, in AD, a treatment benefit was seen with donanemab-azbt using the observer-reported outcome, Alzheimer’s Disease Cooperative Study - instrumental activities of daily living (ADCS-iADL) measure.
CONCLUSIONS: PROs may not detect the benefit of treatment for degenerative diseases. A potential explanation is misalignment in patient expectations. Future research is needed to evaluate how treatment benefits can be appropriately captured by patient experience data.