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Aktuelle Neurologie 2011; 38(05): 242-252
DOI: 10.1055/s-0031-1284393
Originalarbeit
George Thieme Verlag KG Stuttgart · New York

Indirekte Metaanalyse randomisierter plazebokontrollierter klinischer Studien zu Rasagilin und Selegilin in der symptomatischen Behandlung der Parkinson-Krankheit

Indirect Meta-Analysis of Randomised Placebo-Controlled Clinical Trials of Rasagiline and Selegiline in the Symptomatic Treatment of Parkinson′s Disease
W. H. Jost
1   Deutsche Klinik für Diagnostik, Wiesbaden
,
M. Friede
2   Lundbeck GmbH, Scientific Unit, Hamburg
,
J. Schnitker
3   Institut für Angewandte Statistik, Bielefeld
› Author Affiliations
Further Information

Publication History

Publication Date:
05 September 2011 (online)

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Zusammenfassung

Einführung:

Selegilin und Rasagilin sind in der Therapie der Parkinson-Krankheit bewährt. Da keine direkten randomisierten kontrollierten Studien durchgeführt wurden, erfolgte eine indirekte Metaanalyse.

Ziel:

Ziel war, die klinische Differenzierung zwischen Rasagilin und Selegilin basierend auf Wirksamkeit und Sicherheit bei idiopathischen Parkinsonsyndrom zu untersuchen.

Methoden:

Grundlage der Literaturrecherche waren Literatur-Datenbanken, Studienregister und Referenzen relevanter Publikationen. Studien wurden gemäß den Jadad- und Delphi-Kriterien ausgewählt. Die Analyse erfolgte anhand eines Modells mit fixen Effekten basierend auf standardisierten Mittelwertdifferenzen für Wirksamkeitskriterien und Risikodifferenzen der Sicherheitsoutcomes. Als Outcomes wurden UPDRS-Gesamtscore (primäres Outcome) und UPDRS-Motor-Score, Mental-Score und Aktivitäten des täglichen Lebens, die Schwab- und England-Skala, die Off Zeit sowie Sicherheit als sekundäre Outcomes verwendet.

Ergebnisse:

Rasagilin zeigte einen statistisch signifikanten Vorteil im primären Endpunkt des UPDRS-Gesamtscores (Monotherapie: p=0,048, Sensitivitätsanalyse: p=0,023; gepoolte Analysen: p=0,043, Sensitivitätsanalyse: p=0,014) und im sekundären UPDRS-Motor-Score (Monotherapie: p=0,049, Sensitivitätsanalyse: p=0,031; gepoolte Analysen: nicht signifikant; Sensitivitätsanalyse: p=0,046). Für die übrigen sekundären Outcome-Parameter wurde ein numerischer Vorteil für Rasagilin festgestellt. Abbruchraten aufgrund unerwünschter Ereignisse zeigten eine Tendenz zugunsten von Rasagilin. Das Risiko unerwünschter Ereignisse, wie Schwindelgefühl, Halluzinationen, Diarrhoe und Synkope, war unter Rasagilin geringer (je p<0,15).

Fazit:

Die indirekte Metaanalyse zeigte einen statistisch signifikanten und klinisch relevanten Vorteil für Rasagilin gegenüber Selegilin im primären Endpunkt. Die Überlegenheit von Rasagilin wurde auch mit numerischen Vorteilen bei Verträglichkeit und Sicherheit belegt.

Abstract

Introduction:

Selegiline and rasagiline are established in the treatment of Parkinson′s disease. As no direct randomised controlled trials on these drugs are available, an indirect meta-analysis was conducted.

Objective:

Goal of the meta-analysis was to examine the clinical differentiation between rasagiline and selegiline based on efficacy and safety in idiopathic Parkinson′s disease.

Methods:

Literature databases, study registries and references of relevant publications were the basis of our literature search. Studies were selected according to Jadad and Delphi criteria. The analysis used a fixed effects model based on standardised mean differences for efficacy criteria and risk differences of safety outcomes. As outcomes UPDRS (primary) and UPDRS motor functions, mental and ADL, the Schwab and England scale, the off-time as well as safety as secondary outcomes were used.

Results:

Rasagiline showed a statistically significant advantage in the primary endpoint UPDRS total scores (monotherapy: p=0.048, sensitivity analysis: p=0.023; pooled analyses: p=0.043, sensitivity analysis p=0.014) and the secondary endpoint UPDRS motor functions (monotherapy: p=0.049, sensitivity analysis p=0.031; pooled analyses: not significant, sensitivity analysis: p=0.046). For the other secondary outcome parameters, a numerical advantage for rasagiline was found. Discontinuation rates due to adverse effects showed a tendency in favour of rasagiline. Risk for adverse events such as dizziness, hallucinations, diarrhoea and syncope were lower with rasagiline than selegiline (each p<0.15).

Conclusion:

This meta-analysis showed a statistically significant and clinically relevant advantage for rasagiline over selegiline in the primary endpoint. The superiority of rasagiline was further substantiated with advantages in tolerability and safety.

Schlüsselwörter

Metaanalyse - Rasagilin - Selegilin - klinische Studie - Parkinson

Keywords

meta-analysis - rasagiline - selegiline - clinical trials - Parkinson′s disease
 

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