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.
A double-blind, delayed-start trial of rasagiline in Parkinson's disease / Olanow, Cw; Rascol, O; Hauser, R; Feigin, Pd; Jankovic, J; Lang, A; Langston, W; Melamed, E; Poewe, W; Stocchi, F; Tolosa, E; ADAGIO STUDY, Investigators; Collaborators, ; Bueri, J; Garretto, N; Gershanik, O; Giannaula, R; Micheli, F; Wolf, E; Guttman, M; Hobson, D; Jog, M; King, D; Mendis, T; Miyasaki, J; Panisset, M; Pourcher, E; Rajput, A; Ranawaya, R; Tsui, J; Cesaro, P; Damier, P; Destee, A; Durif, F; Slaoui, T; Tison, F; Viallet, F; Deuschl, G; Gasser, T; Ludolph, A; Oehlwein, C; Przuntek, H; Reifschneider, G; Schnitzler, A; Trenkwalder, C; Bokor, M; Katona, A; Lajtos, J; Nikl, J; Takats, A; Valikovics, A; Badarny, S; Djaldetti, R; Giladi, N; Hassin, S; Rabey, Jm; Reches, A; Schwartz, M; Wirguin, I; Albanese, A; Bentivoglio, A; Bonuccelli, U; Calzetti, S; Comi, G; Curatola, L; Ferrarese, C; Lamberti, P; Marconi, R; Martignoni, E; Meco, Giuseppe; Ruggieri, Stefano; Stocchi, F; Bomhof, Ma; Hovestadt, A; Krul, Jm; Leenders, Kl; Cunha, L; Ferreira, J; Bajenaru, Oa; Carciumaru, N; Bulboaca, Ac; Pascu, I; Simu, M; Calopa, M; FERNÁNDEZ GARCÍA, Jm; Kulisevsky, J; Linazasoro, C; Miquel, F; Posada, Ij; Martí, Mj; Burn, D; Macmahon, D; Barker, R; Allen, N; Barbour, P; Bertoni, J; Bharucha, K; Bose, S; Drasby, E; Elble, R; Elmer, L; Evans, B; Factor, S; Fernandez, H; Friedman, J; Hull, K; Golbe, L; Goudreau, J; Guttuso, T; Hassan, M; Hauser, R; Hermanowicz, N; Houser, M; Hurtig, H; Isaacson, S; Jennings, D; Kompoliti, A; Morgan, J; Murphy, J; Nausieda, P; Pahwa, R; Parashos, S; O'Suilleabhain, P; Racette, B; Reich, S; Roberts, J; Rothstein, T; Sahay, A; SAINT HILAIRE, M; Schiess, M; Scott, B; Shahed, J; Simuni, T; Singer, C; Smith, R; Struck, L; Sutton, J; Swope, D; Tagliati, M; Tetrud, J; Togasaki, D; Watts, R.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 361:(2009), pp. 1268-1278. [10.1056/NEJMoa0809335]
A double-blind, delayed-start trial of rasagiline in Parkinson's disease.
MECO, Giuseppe;RUGGIERI, Stefano;
2009
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
