Objective: 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-stage Parkinson’s disease (PD).

Background: In clinical research, MDS-UPDRS Part III is typically used to compare populations via a mean change from baseline score comparison. Although such a metric is useful for overall population comparison, it does not provide sufficient information on the individual experience of motor progression where a threshold of change on MDS-UPDRS Part III is required. This threshold is useful for clinical monitoring of individual patients and understanding differences in the proportion of patients experiencing motor progression in a clinical trial; it is also necessary for defining the event in a time-to-motor progression endpoint.

Method: Data were used (N=316; OFF state for MDS-UPDRS Part III) from the Phase II PASADENA study (NCT03100149). The Clinical Global Impression-Improvement (CGI-I was selected as the anchor. Spearman correlations between change from baseline scores for MDS-UPDRS Part III and CGI-I were conducted at Weeks 24 and 52. Empirical cumulative distribution function (eCDF curves for change in MDS-UPDRS Part III scores were plotted for each of the CGI-I response categories at Weeks 24 and 52. To estimate the MWPWT, the mean and median MDS-UPDRS Part III scores were calculated using data from the first visit at which individuals were rated as “Minimally worse” on the CGI-I.

Results: 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.

Conclusion: 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 early-stage PD (NCT04777331).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/estimating-the-meaningful-within-patient-change-threshold-for-the-mds-updrs-part-iii/