Wirksamkeit und Sicherheit von Safinamid als Zusatztherapie zu Levodopa bei Parkinson-Patienten: eine nicht-interventionelle Beobachtungsstudie

Zusammenfassung

Ziel Safinamid (Xadago^®) ist ein neu zugelassener selektiver MAO-B-Hemmer zur Behandlung der Parkinson-Erkrankung. Die X-TRA Studie untersuchte die Wirksamkeit und Verträglichkeit der Substanz unter Praxisbedingungen.

Methoden Prospektive Beobachtungsstudie bei unselektierten Patienten unter Beachtung der Produktspezifikationen mit deskriptiver Auswertung.

Ergebnisse Von den eingeschlossenen 299 Patienten (65,9 % Männer, Alter 72,7 ± 9,0 Jahre, Krankheitsdauer 7,8 ± 5,9 Jahre) erhielten zu Dokumentationsbeginn 229 Patienten L-Dopa, 108 ein L-Dopa enthaltendes Kombinationsmedikament, 172 einen Dopaminagonisten und 23 einen COMT-Hemmer. 203 Patienten wurden über 6 Monate nachbeobachtet. Der MDS-UPDRS Part III Score für motorische Symptome verringerte sich von einem Ausgangswert von 48,2 ± 22,1 Punkten zum Studienende um 6,8 ± 14,5 Punkte, der Non-Motor Symptoms Scale Score für das Vorhandensein bzw. die Schwere von nicht-motorischen Symptomen von 57,6 ± 42,1 Punkten um 9,3 ± 2,1 Punkte, und der Abnormal Involuntary Movement Score von 4,6 ± 5,8 Punkten um 0,9 ± 2,7 Punkte. Der Parkinson’s Disease Score (PDQ-8) zur Beurteilung der Lebensqualität nahm als Ausdruck einer Verbesserung von 39,4 ± 18,2 Punkten bei Beobachtungsbeginn um 4,3 ± 13,7 Punkte ab. Insgesamt wurden 300 unerwünschte Ereignisse (UAW) bei 132 Patienten, davon 53 SAEs bei 15 Patienten, als mit Safinamid in Zusammenhang stehend klassifiziert. Wegen UAW beendeten 74 Patienten die Safinamid-Therapie vorzeitig.

Schlussfolgerungen Unter Safinamid-Therapie verbesserten sich die motorischen und nicht-motorischen Symptome sowie die Lebensqualität. Die meisten Patienten vertrugen die Therapie gut; es traten nur Nebenwirkungen auf, die bereits in der Patienteninformation gelistet waren.

Abstract

Aim Safinamide (Xadago^®) is a newly approved selective MAO-B inhibitor for the treatment of Parkinson's Disease (PD). The X-TRA study investigated the efficacy and tolerability of the substance under clinical practice conditions.

Methods Prospective, observational study in unselected patients in line with safinamide product specifications.

Results Of the 299 patients included (65.9 % males, age 72.7 ± 9.0 years, duration of disease 7.8 ± 5.9 years), at the beginning of the documentation 229 patients (81.2 %) received L-dopa, 108 (39.3 %) combination drugs containing L-dopa, 172 (59.3 %) a dopamine agonist and 23 (8.3 %) a COMT inhibitor. Of these, 203 patients were followed-up over a period of 6 months. The MDS-UPDRS Part III score for motor symptoms decreased from a baseline value of 48.2 ± 22.1 points by 6.8 ± 14.5 points at the end of the study. The Non-Motor Symptoms Scale score indicating the presence or absence of motor symptoms decreased from a baseline value of 57.6 ± 42.1 by 9.3 ± 2.1 points, the Abnormal Involuntary Movement Score from 4.6 ± 5.8 points by 0.9 ± 2.7 points.

The Parkinson's Disease Score (PDQ-8) for assessing quality of life decreased from a baseline value of 39.4 ± 18.2 points by 4.3 ± 13.7 points, reflecting an improvement. In total, 300 adverse events were classified as related to safinamide in 132 patients (44.1 %). Fifty-three events were serious (in 15 patients; 5 %). Seventy-four patients (24.7 %) discontinued safinamide therapy because of adverse drug reactions.

Conclusions Safinamide therapy improved the motor and non-motor symptoms as well as the quality of life in PD. Most patients tolerated the therapy well. The only side effects that occurred are those described in the patient information leaflet.

Schlüsselwörter

Morbus Parkinson - nicht-interventionell - Fragebögen - Behandlungsmuster - Wirksamkeit - motorische Symptome - Verträglichkeit

Keywords

Parkinson's disease - non-interventional study - safinamide - effectiveness - compatibility

• Literatur

• 1 Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J. et al. Parkinson disease. Nature Reviews Disease Primers 2017; 3: 17 013 .
• 2 Jost WH. Urological problems in Parkinson’s disease: clinical aspects. J Neural Transm (Vienna) 2013; 120 (04) : 587-91 .
• 3 Jost WH. An update on the recognition and treatment of autonomic symptoms in Parkinson’s disease. Expert Rev Neurother 2017; 17 (08) : 791-99 .
• 4 Riedel O, Bitters D, Amann U, Garbe E, Langner I. Estimating the prevalence of Parkinson’s disease (PD) and proportions of patients with associated dementia and depression among the older adults based on secondary claims data. Int J Geriatr Psychiatry 2016 (online first).
• 5 Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K. , et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 2007; 68 (05) : 384-6 .
• 6 Dorsey ER, Bloem BR. The Parkinson Pandemic-A Call to Action. JAMA Neurol 2018; 75 (01) : 9-10 .
• 7 Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA 2014; 311 (16) : 1670-83 .
• 8 Jimenez-Shahed J. A review of current and novel levodopa formulations for the treatment of Parkinson’s disease. Ther Deliv 2016; 7 (03) : 179-91 .
• 9 Ceravolo R, Rossi C, Del Prete E, Bonuccelli U. A review of adverse events linked to dopamine agonists in the treatment of Parkinson’s disease. Expert Opin Drug Saf 2016; 15 (02) : 181-98 .
• 10 Marsala SZ, Gioulis M, Ceravolo R, Tinazzi M. A systematic review of catechol-0-methyltransferase inhibitors: efficacy and safety in clinical practice. Clin Neuropharmacol 2012; 35 (04) : 185-90 .
• 11 Rascol O, Perez-Lloret S, Ferreira JJ. New treatments for levodopa-induced motor complications. Mov Disord 2015; 30 (11) : 1451-60 .
• 12 Perez-Lloret S, Rascol O. The safety and efficacy of safinamide mesylate for the treatment of Parkinson’s disease. Expert Rev Neurother 2016 : 1-14 .
• 13 Fabbri M, Rosa MM, Abreu D, Ferreira JJ. Clinical pharmacology review of safinamide for the treatment of Parkinson’s disease. Neurodegener Dis Manag 2015; 5 (06) : 481-96 .
• 14 Faulkner MA. Safety overview of FDA-approved medications for the treatment of the motor symptoms of Parkinson’s disease. Expert Opin Drug Saf 2014; 13 (08) : 1055-69 .
• 15 Caccia C, Maj R, Calabresi M, Maestroni S, Faravelli L, Curatolo L. et al. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology 2006; 67 (7 Suppl 2): S18-23 .
• 16 Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D. et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord 2014; 29 (02) : 229-37 .
• 17 Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt MH, Chirilineau D. et al. Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease. Mov Disord 2014; 29 (10) : 1273-80 .
• 18 Schapira AH, Fox SH, Hauser RA, Jankovic J, Jost WH, Kenney C. et al. Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol 2017; 74 (02) : 216-24 .
• 19 Uebelacker LA, Epstein-Lubow G, Lewis T, Broughton MK, Friedman JH. A survey of Parkinson’s disease patients: most bothersome symptoms and coping preferences. J Parkinsons Dis 2014; 4 (04) : 717-23 .
• 20 Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT. et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Mov Disord 2007; 22 (01) : 41-7 .
• 21 Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P. et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: Results from an international pilot study. Mov Disord 2007; 22 (13) : 1901-11 .
• 22 Jost W, Fuchs G, Reifschneider G, Odin P, Storch A, Ebersbach G. Validation of a German version of the NMSS (Non-Motor Symptom assessment Scale). Klin Neurophysiol 2010 ;41 – ID5.
• 23 Guy W. ECDEU Assessment Manual for Psychopharmacology – Revised (DHEW Publ No ADM 76-338), US Department of Health, Education and Welfare; 1976 .
• 24 Buhmann C, Rizos A, Emmans D, Jost WH. [Intercultural adaptation of the AIMS in German language: A scale for abnormal involuntary movements]. Nervenarzt 2016; 87 (04) : 411-7 .
• 25 Jenkinson C, Fitzpatrick R, Peto V, Greenhall RHyman N. The PDQ-8: Development and validation of a short-form parkinson’s disease questionnaire. Psychology & Health 1997; 12 (06) : 805-14 .
• 26 Deutschen Gesellschaft für Neurologie (DGN). Parkinson-Syndrome – Diagnostik und Therapie. Leitlinie Stand: 30. 09.2012(in Überarbeitung), gültig bis 31. 12.2015;AWMF Registernummer 030 / 010. Internet: http://www.awmf.org/leitlinien/detail/ll/030-010.html . Zugriff am 1.7.2016.
• 27 Horvath K, Aschermann Z, Acs P, Deli G, Janszky J, Komoly S. et al. Minimal clinically important difference on the Motor Examination part of MDS-UPDRS. Parkinsonism Relat Disord 2015; 21 (12) : 1421-6 .
• 28 Cattaneo C, Barone P, Bonizzoni E, Sardina M. Effects of Safinamide on Pain in Fluctuating Parkinson’s Disease Patients: A Post-Hoc Analysis. J Parkinsons Dis 2017; 7 (01) : 95-101 .
• 29 European Medicines Agency. Xadago (EMEA / H/C / 002396 -N / 0018) Summary of Product Information (Stand 13 Juni 2017). Internet: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002396/WC500184965.pdf Zugriff am 19 Januar 2018 .