The Evidence for Disease Modification in Parkinson's Disease

Figures & data

FIGURE 1.  The hazard ratio for the comparison of subjects taking deprenyl (with placebo or tocopherol) with subjects not taking deprenyl (placebo only or tocopherol with placebo) with respect to the risk of reaching the end point per unit of time is 0.50 (p < 0.001; 95 percent confidence interval, 0.41 to 0.62). The period of analysis was the time from base line to the last evaluation during treatment. The number of subjects evaluated in each group is shown under each time point. (Reproduced with permission from Reference [7]).

FIGURE 2.  In both panels shown here, the active medication provides a benefit in comparison with placebo. (A) Symptomatic: the substitution of placebo with the active drug (delayed-start) provides a benefit that allows the group to “catch up” with the early-start group, showing a similar improvement in disability at the end of phase B—this outcome is in favor in a purely symptomatic effect. (B) “Disease-modifying”: the delayed introduction of the active drug after placebo does not provide a benefit euqal to that observed when patients start active treatment early, and the difference persists throughout phase B. This result shows that patients starting therapy early did better than those who started late, and cannot be explained by a simple symptomatic effect. It is in favor of a disease-modification effect, regardless of the fact that this could be due to “neuroprotection” or enhancement of early compensatory mechanisms. (Reproduced with permission from Reference [13]).

FIGURE 3.  Mean (± 1 SE) change in the Unified Parkinson's Disease Rating Scale (UPDRS) score for each group. A, Total unadjusted UPDRS score by visit for each treatment group for the 371 subjects included in the efficacy cohort. For the efficacy cohort, the last observation was carried forward for subjects with missing values for a given visit. (Reproduced with permission from Reference [15]).

FIGURE 4.  Mean percent change from TEMPO baseline in total UPDRS scores: early-start versus delayed-start with rasagiline (N = 404). Overall difference between early-start and delayed-start groups is 16% (RMA; p = 0.006). Numbers in parentheses () represent numbers of subjects remaining on rasagiline at each time point. The analysis of UPDRS scores was performed at each time point according to available patient visits, and not necessarily synchronized with TEMPO placebo-controlled and active-treatment phases shown in Figure 1. Bars indicate standard errors. Data from year 6.5 are combined with data from year 6. (Reproduced with permission from Reference [16]).

FIGURE 5.  The mean (±SE) change from baseline in the UPDRS score in the efficacy cohort for the second and third primary end points for patients receiving rasagiline at a dose of 1 mg per day (Panel A) and those receiving 2 mg per day (Panel B) are shown. The dashed lines indicate placebo, and the solid lines indicate rasagiline. (Reproduced with permission from Reference [17]).