To estimate the meaningful within-patient worsening threshold (MWPWT) of the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III in early Parkinson’s disease (ePD).

Progressor and time-to-progression endpoints can provide a useful means for assessing treatment efficacy. For the MDS-UPDRS Part III, Horváth et al. (2015) estimated an MWPWT (required for these endpoints) of 5 points. Convergence of evidence supporting an MWPWT from multiple sources provides greater confidence in the estimate. Thus, these anchor-based estimation analyses were replicated.

Correlations of 0.31–0.32, and separation of eCDF curves were identified, supporting the use of CGI-I as an anchor. Overall, 251 patients had a CGI-I rating of ‘Minimally worse’ at a post-baseline visit, for whom a mean (median) value of 4.98 (5.00) points on MDS-UPDRS Part III was identified. This supports a MWPWT of 5 points.

These findings indicate that a 5-point increase on MDS-UPDRS Part III can be used as a threshold for meaningful worsening of motor signs. This supports the use of time-to-5-point increase on MDS-UPDRS Part III as the primary endpoint for the Phase IIb PADOVA study, an ongoing randomised, double-blind, placebo-controlled study evaluating the efficacy of prasinezumab in ePD (NCT04777331).