Real world data of a German Parkinson’s disease population: effectiveness and safety of safinamide in routine clinical practice

Abstract

Background

Parkinson’s Disease (PD) is a common progressive neurodegenerative disorder that leads to an imbalance of various neurotransmitters and affects cognitive, motor and non-motor function. Safinamide inhibits monoamine oxidase B in a highly selective and reversible manner and beyond that has anti-glutamatergic properties, with positive effects on motor and non-motor symptoms. The aim of the study was to obtain data about the effectiveness and tolerability of safinamide under routine clinical practice conditions in unselected patients with Parkinson’s disease (PD).

Methods

A post-hoc analysis of the German cohort of the European SYNAPSES study (a non-interventional cohort study). Patients were treated with safinamide as an add-on to levodopa and followed-up for 12 months. Analyses were done in the total cohort and in clinically relevant subgroups (patients older than 75 years; with relevant comorbidities; with psychiatric conditions).

Results

181 PD patients were eligible for analysis. Motor symptoms included bradykinesia (76.8%), rigidity (77.3%), tremor (58.6%), and postural instability (27.1%). Non-motor symptoms were reported in 161 patients (89.0%), mainly psychiatric symptoms (43.1%), sleep disorders (35.9%), fatigue (30.9%), and pain (27.6%). 28.7% of patients were aged 75 years or older, 84.5% had relevant comorbidities, and 38.1% had psychiatric conditions. During treatment, the rate of motor complications decreased from 100.0% to 71.1%. UPDRS scores improved under safinamide, with a clinically important effect in 50% in the total score and 45% in the motor score. The positive effect on motor complications occurred already at the 4-month visit and was maintained over 12 months. At least one adverse event (AE)/adverse drug reaction (ADR) was reported by 62.4%/25.4% of patients, AEs were generally mild or moderate, and completely resolved. Only 5 (1.5%) AEs had a definite relationship to safinamide.

Conclusions

The benefit-risk profile of safinamide was favourable and consistent with the total cohort of the SYNAPSES study. In the subgroups, findings were congruent with the total population, which allows the clinical utilisation of safinamide also in more vulnerable patient groups.

Keywords:

• Parkinson’s disease
• safinamide
• MAO-B inhibitor
• anti-glutamatergic
• real-world evidence
• Germany
• effectiveness
• safety

Transparency

Declaration of funding

The SYNAPSES study was funded by Zambon S.p.A, the present analysis by Zambon GmbH, Berlin, Germany.

Declaration of financial/other relationships

Wolfgang H. Jost has received consultancy fees from Zambon. Ivonne Gluth, Jennifer C. Lück, Olga I. Fonseca da Cruz Lopes are employees of Zambon. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors contributed to writing and reviewing the manuscript and approved the final manuscript.

Acknowledgements

The authors thank the investigators and the patients involved in the trial. In Germany, the following investigators contributed to the study: Blersch WK, Delf M, Hellwig B, Herbst HP, Kupsch A, Jost WH, Lang M, Muhlack S, Nastos I, Oehlwein C, Schlegel E, Schwarz J, Warnecke T, Woitalla D.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation upon request.

Ethics statement

The study was designed, in agreement with the European Agency (EMA), to investigate how safinamide is prescribed and used in routine clinical practice and to collect safety and effectiveness data. Both protocol and patient materials were approved by Independent Ethics Committees and Health Authorities of the participating countries. All patients signed informed and privacy consent forms and the study was conducted according to the ethical standards of the institutional and/or national research committee and according to the Declaration of Helsinki. Personal data were collected, stored, and processed exclusively in pseudonymized form and in compliance with the regulatory requirements for the protection of confidentiality of patients. The patients/participants provided their written informed consent to participate in this study.

Trial registration

EUPAS-13745 https://www.encepp.eu/encepp/viewResource.htm?id=41165 Registered 9. June 2016.