Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study

• Published in: Journal of the neurological sciences 2024-06, Vol.461, p.123051, Article 123051
• Main Authors: Nishikawa, Noriko, Hatano, Taku, Nishioka, Kenya, Ueno, Shin-Ichi, Saiki, Shinji, Nakamura, Ryota, Yoritaka, Asako, Ogawa, Takashi, Shimo, Yasushi, Sako, Wataru, Shimura, Hideki, Furukawa, Yoshiaki, Kamei, Takanori, Ishida, Takayuki, Hattori, Nobutaka
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alanine - analogs & derivatives; Alanine - therapeutic use; Antiparkinson Agents - adverse effects; Antiparkinson Agents - therapeutic use; Benzylamines - adverse effects; Benzylamines - therapeutic use; Drug Therapy, Combination; East Asian People; Female; Humans; Japan; Levodopa - adverse effects; Levodopa - therapeutic use; Male; MAO-B inhibitor; Middle Aged; Pain; Parkinson Disease - drug therapy; Parkinson's disease; Quality of life; Safinamide; Severity of Illness Index; Treatment Outcome; Wearing-off
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2024.123051

Safinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. This multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. In total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change −7.0 [p = 0.012], −2.4 [p = 0.007] and − 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. Safinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. University Hospital Medical Information Network in Japan; study ID: UMIN000044341. •Safinamide can benefit patients with PD in the early stages of wearing-off in clinical practice.•Safinamide improved motor fluctuation, motor/non-motor symptoms and quality of life.•Safinamide reduced OFF-period pain and nocturnal pain.