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Background A therapy that slows disease progression is the major unmet need in Parkinson's disease.
Methods In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72.
Results Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (±SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09±0.02 points per week in the early-start group vs. 0.14±0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82±0.53 points in the early-start group vs. 4.52±0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085±0.02 points per week in the early-start group vs. 0.085±0.02 points per week in the delayed-start group, P<0.001). All three end points were not met with rasagiline at a dose of 2 mg per day, since the change in the UPDRS score between baseline and week 72 was not significantly different in the two groups (3.47±0.50 points in the early-start group and 3.11±0.50 points in the delayed-start group, P=0.60).
Conclusions Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect, but early treatment with rasagiline at a dose of 2 mg per day did not. Because the two doses were associated with different outcomes, the study results must be interpreted with caution. (ClinicalTrials.gov number, NCT00256204
[ClinicalTrials.gov]
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Source Information
From the Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York (C.W.O.); INSERM CIC-9302 and UMR-825, Departments of Clinical Pharmacology and Neurosciences, Centre Hospitalier Universitaire and University of Toulouse, Faculty of Medicine, Toulouse, France (O.R.); the Department of Neurology, University of South Florida, Tampa (R.H.); the Department of Industrial Engineering and Management, Technion–Israel Institute of Technology, Haifa, Israel (P.D.F.); the Department of Neurology, Baylor College of Medicine, Houston (J.J.); the Division of Neurology, University of Toronto, Toronto (A.L.); California Parkinson Institute, Sunnyvale (W.L.); the Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tikva, and Sackler School of Medicine, Tel Aviv — both in Israel (E.M.); the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.); Institute of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome (F.S.); and the Department of Neurology, University of Barcelona, Barcelona, and Centro de Investigacíon Biomédica en Red Sobre Enfermedades Neurodegenerativas, Madrid (E.T.).
Drs. Olanow and Rascol contributed equally to this article.
Address reprint requests to Dr. Olanow at the Department of Neuroscience, Mount Sinai School of Medicine, 1 Gustave Levy Pl., Annenberg 14-94, New York, NY 10029, or at warren.olanow{at}mssm.edu.
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