Objective: To compare  efficacy and safety of safinamide and rasagiline as adjunctive treatment to levodopa in Chinese patients with Parkinson’s disease (PD) by matching-adjusted indirect comparison (MAIC).

Background: Adjuncts to levodopa are required for PD motor fluctuations, including safinamide and rasagiline^[1,2]. However, head-to-head studies comparing safinamide and rasagiline are not available.

Method: Anchored MAIC was conducted using individual patient data from XINDI study^[3] (safinamide from 50 to 100 mg/day after 14 days, 16 weeks, n=350) and aggregated data from Zhang’s study^[4] (rasagiline 1 mg/day, 16 weeks, n=310). Baseline age, sex, BMI and off-time were adjusted for matching. Primary efficacy outcome was the mean change in total daily off-time from baseline to endpoint. Secondary efficacy outcomes were the mean changes in the UPDRS III during on phase and PDQ-39. Least-squares mean of primary efficacy outcome was recalculated by a weighted covariance model, with the study centers and treatment as fixed factors and baseline off-time as a covariate. A similar statistical method was applied to secondary outcomes. Safety outcomes included rates of adverse events (AEs), serious adverse events (SAEs), and discontinuations due to AEs. Bucher method ^[5] was used for mean difference (MD) of efficacy and odds ratio (OR) of safety outcomes, each with 95% confidence interval (CI).

Results: Effective sample size was 271 after matching [Table1]. Combination therapy of safinamide 100mg/day and levodopa significantly reduced off-time by 0.7 hours (-0.7, -1.40 to -0.02) compared to rasagiline 1mg/day. Safinamide more effectively reduced UPDRS III (-2.9, -5.28 to -0.52). Changes in PDQ-39 summary index (-2.2, -5.26 to 0.84), activities of daily living (-0.6, -5.44 to 4.24), emotional well-being (-3.2, -8.36 to 1.90), mobility (-3.5, -7.84 to 0.84) and stigma (-3.9, -9.27 to 1.57) indicated a trend toward greater improvement in safinamide. There was no significant difference in AEs (1.6, 0.83 to 3.19), SAEs (1.1, 0.21 to 6.14), and discontinuations due to AEs (0.7, 0.14 to 3.28) [Table2].

Conclusion: Compared to rasagiline 1 mg/day, safinamide 100 mg/day as adjunctive treatment to levodopa can significantly reduce motor fluctuations and improve motor symptoms in Chinese PD patients, maintaining a comparable quality of life and safety.

[Table 1]

[Table 2]

References: [1] Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020;323(6):548-560. doi:10.1001/jama.2019.22360
[2] Yan R, Cai H, Cui Y, et al. Comparative efficacy and safety of monoamine oxidase type B inhibitors plus channel blockers and monoamine oxidase type B inhibitors as adjuvant therapy to levodopa in the treatment of Parkinson’s disease: a network meta-analysis of randomized controlled trials. Eur J Neurol. 2023;30(4):1118-1134. doi:10.1111/ene.15651
[3] Wei Q, Tan Y, Xu P, et al. The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson’s Disease with Motor Fluctuations. CNS Drugs. 2022;36(11):1217-1227. doi:10.1007/s40263-022-00958-6
[4] Zhang Z, Shao M, Chen S, et al. Adjunct rasagiline to treat Parkinson’s disease with motor fluctuations: a randomized, double-blind study in China. Transl Neurodegener. 2018;7:14. doi:10.1186/s40035-018-0119-7
[5] Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997;50(6):683-691. doi:10.1016/s0895-4356(97)00049-8

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-matching-adjusted-indirect-comparison-of-efficacy-and-safety-for-safinamide-versus-rasagiline-as-adjunctive-treatment-to-levodopa-in-chinese-patients-with-parkinsons-disease/