J009 PROOF-HD: changes in q-motor and cuhdrs show an alignment of objective measures and clinical scales, and the capability of q-motor to predict long-term clinical outcomes

<h3>Background</h3> Q-Motor measures lack rater-bias and revealed higher sensitivity and consistency than clinical scales in several trials, but little is known about the relationship of treatment responses between Q-Motor and clinical scales. Observational studies and clinical trials show correlation between longitudinal worsening in the objective measures of Q-Motor and worsening in clinical progression as assessed by cUHDRS, TFC, and TMS. <h3>Objective</h3> To assess correlations between the benefit of pridopidine in Q-Motor and measures of clinical progression, and to determine the predictive value of early benefits in Q-Motor towards later improvements in measures of clinical progression and function. <h3>Methods</h3> In PROOF-HD, the primary Q-Motor tapping endpoint ‘Inter-Onset-Interval’ (IOI) was analyzed in the ‘finger-tapping’ (digitomotography) and ‘pronate/supinate-hand-tapping’ (dysdiadochomotography) tasks. Correlations between changes in IOI and changes in cUHDRS and TFC at weeks 26, 52, 65 and 78 were calculated. A causal inference model adjusting for natural disease progression and baseline characteristics was applied to assess the relationship of these changes with pridopidine treatment. In addition, we assessed whether early changes to 26 weeks correlate with changes to later visits up to week 78. <h3>Results</h3> Changes in IOI and the cUHDRS were correlated at all visits in finger-tapping [r=-0.26–-0.41, p&lt;0.0001] and pronate/supinate-tapping [r=-0.17–-0.30, p=0.0038–p&lt;0.0001]. Early Q-Motor improvements at 26 weeks were correlated to benefits in cUHDRS at later visits, up to week 78 in finger-tapping [r=-0.17–-0.23, p=0.0048–p=0.00018] and pronate-supinate-tapping [r=-0.12–-0.19, p=0.036–r=0.0057]. The causal-interference-model confirmed these findings with significant relationships detected for treatment induced changes at all visits for both tasks [all p&lt;0.0001]. The model suggests that every 10 msec benefit of pridopidine in finger-tapping is associated with an average of 0.1 less decline in cUHDRS (p&lt;0.0001). Similar observations were seen with the TFC. <h3>Conclusion</h3> The correlation of observed changes in Q-Motor measures and cUHDRS and TFC suggest an alignment of objective measures and clinical scales in the assessment of treatment effects in PROOF-HD up to week 78. Furthermore, Q-Motor effects at 26 weeks are highly predictive of changes in cUHDRS and TFC at later visits.