Long-term effects of rasagiline and the natural history of treated Parkinson's disease.

Background: The Attenuation of Disease progression with Azilect GIven Once-daily (ADAGIO) delayed-start study demonstrated a benefit of early-start treatment with rasagiline 1 mg/day versus delayed-start treatment in PD. This follow-up study aimed to assess whether these benefits persist and the clinical progression rate during long-term naturalistic treatment.

Methods: The ADAGIO Follow-Up study was initiated approximately 26 months after completion of the ADAGIO study. Patients were followed for 3 years and were treated in an open-label manner with rasagiline 1 mg/day and any other PD treatment that was deemed appropriate. Changes from follow-up baseline to study end in UPDRS scores, and the emergence of clinical milestones (including unsteady gait and/or balance impairment, falls, freezing of gait, and cognitive decline) were assessed.

Results: The study enrolled 683 patients (58% of the full ADAGIO cohort and 72% of ADAGIO completers). At baseline, mean time from diagnosis was 46.9 months and UPDRS total score was 25.6 units. There were no significant differences in UPDRS total or subscale scores or time to any milestone between patients who were in the original ADAGIO early-start group versus those in the delayed-start group. At study end, patients (total cohort) had worsened by a mean ± standard deviation of 6.0 ± 11.6 UPDRS total units, 3.3 ± 8.6 UPDRS motor units and 2.0 ± 4.0 UPDRS activities of daily living (ADL) units. Overall, 43.6% of patients had onset of unsteady gait/balance impairment, 35.7% had fallen, 26.2% had freezing of gait, and 33.1% had cognitive decline.

Conclusions: The ADAGIO Follow-Up study failed to demonstrate long-term benefits of early-start rasagiline treatment in the prior ADAGIO study. Clinically important milestones occurred in a substantial proportion of patients. © 2016 International Parkinson and Movement Disorder Society.