Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study

Abstract

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches.

Objectives: To estimate LED of safinamide 50 and 100 mg.

Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129).

Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED.

Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

Keywords: LED; Parkinson's disease; Rasagiline; levodopa equivalent dose; safinamide.

FIG. 1

Prevalence of motor fluctuations (panel A) and dyskinesias (panel B) in the study population at baseline (gray color) and follow‐up (white color). No iMAO indicates the control group of patients who never received iMAO‐B.

FIG. 2

Adjusted mean difference [95%CI] in total LED change between each active group versus the control group used to calculate LED of Safinamide 50 mg, Safinamide 100 mg, and Rasagiline 1 mg. Each column represents the mean change in total LED between baseline and follow‐up for each study group, adjusted for disease duration, age at assessment, duration of follow‐up and the baseline value. No iMAO indicates the control group of patients who never received iMAO‐B.