Data di Pubblicazione:
2013
Abstract:
Background: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.
Methods: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
Results: Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.
Conclusions: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.)
Tipologia CRIS:
14.a.1 Articolo su rivista
Elenco autori:
Feagan, Bg; Rutgeerts, P; Sands, Be; Hanauer, S; Colombel, Jf; Sandborn, Wj; Van Assche, G; Axler, J; Kim, Hj; Danese, S; Fox, I; Milch, C; Sankoh, S; Wyant, T; Xu, J; Parikh, A; Bampton P, GEMINI 1 Study G. r. o. u. p.; Chung, A; Debinski, H; Florin, T; Hetzel, D; Kronborg, I; Lawrance, I; Leong, R; Macrae, F; Moore, G; Pavli, P; Radford Smith, G; Weltman, M; Haas, T; Reinisch, W; Stockenhuber, F; Vogel, W; De Maeyer, M; De Vos, M; D'Haens, G; Louis, E; Muls, V; Van Assche, G; Petrov, P; Aumais, G; Axler, J; Bitton, A; Bourdages, R; Bressler, B; Cohen, A; Fedorak, R; Greenberg, G; Jones, J; Kutcher, W; Macintosh, D; Ponich, T; Singh, R; Steinhart, H; Sy, R; Douda, L; Lukas, M; Samek, M; Vyhnalek, P; Woznica, V; Zadorova, Z; Andersen, V; Rannem, T; Staun, M; Maelt, A; Margus, B; Bonaz, B; Coffin, B; Desreumaux, P; Laharie, D; Reimund, Jm; Karaus, M; Pace, A; Ross, M; Schmidt, W; Witthoeft, T; Zeitz, M; Karamanolis, D; Mantzaris, G; Maris, T; Ng, C; Gall, J; Hunyady, B; Szepes, A; Toth, T; Vincze, A; Oddsson, E; Jósefsspktali, Kö; Ahuja, V; Amarapurkar, D; Goenka, M; Habeeb, Ma; Jalihal, U; Kalambe, B; Koshy, A; Kumar, R; Prasad, V; Reddy, N; Sekar, T; Shankar, R; Tantry, V; Ryan, B; Avni, Y; Ben Horin, S; Ardizzone, S; Armuzzi, A; Corazziari, E; Danese, S; Fries, Walter; Kohn, A; Lisova, D; George, Am; Hilmi, In; Bhaskaran, Sk; Soon, Sy; Engels, L; Ponsioen, C; Wallace, I; Wyeth, J; Florholmen, J; Jahnsen, J; Lygren, I; Röseth, A; Ciecko Michalska, I; Gonciarz, M; Huk, J; Jamrozik Kruk, Z; Kondusz Szklarz, M; Paradowski, L; Wiechowska Kozlowska, A; Han, Ds; Hong, Sp; Kim, Hj; Kim, Js; Kim, Ko; Kim, Yh; Yang, Sk; Alexeeva, O; Bunkova, E; Burnevich, E; Dolgikh, O; Kasherininova, I; Khovaeva, Y; Lakhin, A; Ling, Kl; Bester, F; Coetzer, T; Grundling Hde, K; Jackson, Ld; Spies, P; Wright, Jp; Ziady, C; Garcia Planella, E; Perez Gisbert, J; Rogler, G; Seibold, F; Kao, Aw; Wu, Dc; Atug, O; Kurdas, Oo; Hawthorne, Ab; Lindsay, J; Abreu, M; Aggarwal, A; Bala, N; Becker, S; Behm, B; Braun, R; Cohn, W; Cross, R; Dar, S; Dassopoulos, T; De Villiers, W; Desta, T; Dryden, G; Duvall, A; Farraye, F; Fein, S; Liu, Bf; Gatof, D; Geenen, D; Ginsburg, P; Glover, S; Gopal, V; Hanauer, S; Hanson, J; Hardi, R; Isaacs, K; Jain, R; Karyotakis, N; Korzenik, J; Koshy, G; Koval, G; Lawitz, E; Lee, S; Loftus, E; Luther, R; Mahadevan, U; Mannon, P; Matsuyama, R; Mcintosh, A; Melmed, G; Mirkin, K; Nichols, M; Oubre, B; Pandak, W; Quadri, A; Quallich, L; Randall, C; Rausher, D; Regueiro, M; Safdi, A; Sands, B; Scherl, E; Schneier, J; Schwartz, D; Sedghi, S; Shafran, I; Siegel, C; Stein, L; Tatum, H; Weinberg, D; Winston, B; Wolf, D; Younes, Z; Feagan, Bg; Colombel, Jf; Hanauer, S; Rutgeerts, P; Sandborn, Wj; Sands, Be; Jewell, D; Mahon, J; Rothstein, R; Snydman, D; Massaro, J; Clifford, D; Berger, J; Major, E; Provenzale, J; Lev M., Abstract
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