Overall Efficacy and Safety of Safinamide in Parkinson’s Disease: A Systematic Review and a Meta-analysis

Abstract

Background and Objective Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes. Methods PubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson’s Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson’s Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel–Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed. Results Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa ( l -dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = − 1.06 h; 95% CI from − 1.60 to − 0.51), and improved UPDRS-III (MD = − 2.77; 95% CI from − 4.27 to − 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = − 1.84; 95% CI from − 3.19 to − 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence. Conclusion Overall, safinamide is effective in PDwMF patients t...

Effectiveness of Safinamide over Mood in Parkinson’s Disease Patients: Secondary Analysis of the Open-label Study SAFINONMOTOR

“…Compared to the score at V1, the change in the score at V2 and V3 for the BDI-II, NMSS mood/ apathy domain, and the PDQ-39 emotional well-being domain was significant too, but differences were not observed between the score from V2 and V3 to V4 for any of the scales (Table 2 and Figs. 1,2,3). With regard to the MDS-IV and Judd criteria, at the baseline visit, 2% (N = 1) of patients presented nonD, 12% (N = 6) subD, 34% (N = 17) mD, and 52% (N = 26) suffered MD.…”

“…The analysis of changes in mood was a secondary objective defined in the study protocol. Patients were enrolled according to the following inclusion criteria: (1) diagnosis of PD according to the UK Parkinson's Disease Society Brain Bank criteria [8]; (2) to have the indication of receiving safinamide according to the neurologist criteria in their clinical practice; (3) to have a Non-Motor Symptoms Scale (NMSS) total score at baseline of at least 40; (4) no dementia criteria with a Mini-Mental State Examination at baseline of at least 26) [9]; (5) to be older than 30 years old; (6) to wish to voluntarily participate and to sign a consent form. Exclusion criteria were (1) to be under MAOB-I (rasagiline or selegiline; a washout period of at least 2 week was allowed); (2) any other contraindication to be treated with safinamide according to product data; (3) incapacity to complete the questionnaires adequately; (4) other disabling concomitant neurological disease (stroke, severe head trauma, neurodegenerative disease, etc.…”

“…This combined mechanism has been suggested to improve NMS by dopaminergic and non-dopaminergic effects. Safinamide is effective in the treatment of motor fluctuations [ 3 ] and NMS [ 4 ]. With regard to mood, very recently, Peña et al [ 5 ] observed in a retrospective study conducted in 82 patients with PD a significant improvement in the Hamilton Depression Rating Scale 3 months after starting with safinamide and suggested that safinamide could be useful for treating depression in PD.…”

Safinamide in the treatment pathway of Parkinson’s Disease: a European Delphi Consensus

“…Safinamide is marketed in Europe and in North America under the brand name of Xadago® (Zambon Pharma) and Onstryv® (Valeo Pharma); it was approved in 2015 as adjunctive therapy to levodopa in mid- to late-stage fluctuating patients and became commercially available in the spring of 2016. While its efficacy in controlling motor symptoms and improving motor fluctuations is well established 9 – 11 , uncertainty remains on its potential ability to control dyskinesias in the long term or to address the many non-motor symptoms that are typical of the advanced stages of the disease. The aim of this study was to obtain a European Consensus on the use of safinamide, considering the efficacy of this compound on motor symptoms and motor complications, its effect on non-motor symptoms (NMS), quality of life in patient with PD and how its clinical effect is perceived by clinicians.…”

Safinamide protects against amyloid β (Aβ)-induced oxidative stress and cellular senescence in M17 neuronal cells

“…Safinamide ( Figure 1(a )) is a reversible inhibitor of MAO-B that has both dopaminergic and glutamatergic functions [ 13 ]. Current evidence suggests that safinamide may be useful for the treatment of multiple neurological disorders including neuromuscular disorders, Parkinson’s disease (PD), stroke, and multiple sclerosis [ 14 , 15 ]. Evidence from multiple preclinical studies has shown that safinamide possesses antioxidant capacity [ 16 ].…”