Objective: To retrospectively review the clinical benefit of safinamide in patients with Multiple System Atrophy.

Background: Safinamide is a new monoamine oxidase-B inhibitor, with dopaminergic and glutamatergic mechanisms, that has recently been approved as an add-on to levodopa for the treatment of Parkinson’s disease (PD) with fluctuations. Improvement in motor cardinal signs, dyskinesia, humour and pain have been suggested at 2-years follow-up. Multiple system atrophy (MSA) is a rare progressive degenerative disorder characterized by autonomic failure, and a variable combination of parkinsonism (P) and cerebellar ataxia, that leads to early severe disability. A subset of MSA-P patients may experience some transitory benefit with levodopa and some develop motor (MF) and nonmotor fluctuations

Method: Four patients with probable or possible MSA-P (according to the second consensus criteria) and MF were treated with safinamide. The initial dose was 50 mg and it was increased according to clinical response: if insufficient (none or partial) clinical benefit, doses were increased to a maximum of 200 mg/day. Clinical charts were retrospectively reviewed.

Results: Patients were 65 ± 9 years-old women, 5.8 ± 2.5 years of disease duration, Hoehn & Yahr (HY) stage of 3 (three patients) and 4 (one patient), treated with levodopa equivalent dose of 1299 ± 584 mg. All had MF (four had motor wearing off, three had morning akinesia), four had OFF freezing of gait (FOG) and three had OFF pain. Median follow-up was 6 months. MF and FOG improved in all patients with 50-100 mg/day of safinamide. HY improved from 3 to 2 in three patients. In one patient wearing OFF pain only remitted with 200 mg/day. The patient on safinamide 50 mg/day developed non-troublesome orofacial dyskinesia. None developed symptomatic orthostatic hypotension nor hallucinations.

Conclusion: Although this is a small group of patients with no control intervention, it seems that, as in PD, safinamide might be helpful in MSA-P patients with MF, FOG and OFF pain. The benefit in OFF FOG and OFF pain might be explained by safinamide’s multimodal pharmacological profile other than dopaminergic. Clinical trials are needed to demonstrate this potential symptomatic benefit.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/is-safinamide-helpful-in-multiple-system-atrophy/