Vedolizumab as induction and maintenance therapy for ulcerative colitis
Brian G Feagan, Paul Rutgeerts, Bruce E Sands, Stephen Hanauer, Jean-Frédéric Colombel, William J Sandborn, Gert Van Assche, Jeffrey Axler, Hyo-Jong Kim, Silvio Danese, Irving Fox, Catherine Milch, Serap Sankoh, Tim Wyant, Jing Xu, Asit Parikh, GEMINI 1 Study Group, Peter Bampton, Alvin Chung, Henry Debinski, Timothy Florin, David Hetzel, Ian Kronborg, Ian Lawrance, Rupert Leong, Finlay Macrae, Greg Moore, Paul Pavli, Graham Radford-Smith, Martin Weltman, Thomas Haas, Walter Reinisch, Felix Stockenhuber, Wolfgang Vogel, Marc De Maeyer, Martine De Vos, Geert D'Haens, Edouard Louis, Vinciane Muls, Gert Van Assche, Plamen Petrov, Guy Aumais, Jeffrey Axler, Alain Bitton, Raymond Bourdages, Brian Bressler, Albert Cohen, Richard Fedorak, Gordon Greenberg, Jennifer Jones, Walter Kutcher, Donald MacIntosh, Terry Ponich, Ranjit Singh, Hillary Steinhart, Richmond Sy, Ladislav Douda, Milan Lukas, Miloslav Samek, Petr Vyhnalek, Vlastimil Woznica, Zdenka Zadorova, Vibeke Andersen, Terje Rannem, Michael Staun, Anu Maelt, Benno Margus, Bruno Bonaz, Benoit Coffin, Pierre Desreumaux, David Laharie, Jean-Marie Reimund, Michael Karaus, Andrea Pace, Matthias Ross, Wolfgang Schmidt, Thomas Witthoeft, Martin Zeitz, Dimitrios Karamanolis, Gerasimos Mantzaris, Theofanis Maris, Carmen Ng, Janos Gall, Bela Hunyady, Attila Szepes, Tamas Toth, Aron Vincze, Einar Oddsson, Kjartan Örvar Jósefsspktali, Vineet Ahuja, Deepak Amarapurkar, Mahesh Goenka, Mohammed Aejaz Habeeb, Umesh Jalihal, Bharat Kalambe, Abraham Koshy, Ramesh Kumar, V G Mohan Prasad, Nageshwar Reddy, T V Sekar, Ravi Shankar, Vishwanath Tantry, Barbara Ryan, Yona Avni, Shomron Ben Horin, Sandro Ardizzone, Alessandro Armuzzi, Enrico Corazziari, Silvio Danese, Walter Fries, Anna Kohn, Diana Lisova, Abraham Mathew George, Ida Normiha Hilmi, Shashi Kumar Menon Bhaskaran, Su Yang Soon, L G J B Engels, C Y Ponsioen, Ian Wallace, John Wyeth, Jon Florholmen, Jörgen Jahnsen, Idar Lygren, Arne Röseth, Irena Ciecko-Michalska, Maciej Gonciarz, Jacek Huk, Zofia Jamrozik-Kruk, Malgorzata Kondusz-Szklarz, Leszek Paradowski, Anna Wiechowska-Kozlowska, Dong Soo Han, Sung Pil Hong, Hyo-Jong Kim, Joo Sung Kim, Kyeong Ok Kim, Young-Ho Kim, Suk-Kyun Yang, Olga Alexeeva, Elena Bunkova, Eduard Burnevich, Oleg Dolgikh, Irina Kasherininova, Yaroslava Khovaeva, Alexander Lakhin, Khoon Lin Ling, Frederik Bester, Thomas Coetzer, H de K Grundling, Leslie David Jackson, Pieter Spies, John Philip Wright, C Ziady, Esther Garcia Planella, Javier Perez Gisbert, Gerhard Rogler, Frank Seibold, Ai-Wen Kao, Deng-Chyang Wu, Ozlen Atug, Oya Ovunc Kurdas, A B Hawthorne, James Lindsay, Maria Abreu, Avanish Aggarwal, Natarajan Bala, Scott Becker, Brian Behm, Robert Braun, William Cohn, Raymond Cross, Seema Dar, Themistocles Dassopoulos, Willem De Villiers, Taddese Desta, Gerald Dryden, Aaron Duvall, Francis Farraye, Steven Fein, Blanche Fung Liu, David Gatof, Daniel Geenen, Philip Ginsburg, Sarah Glover, Vikram Gopal, Stephen Hanauer, John Hanson, Robert Hardi, Kim Isaacs, Rajesh Jain, Nicholas Karyotakis, Joshua Korzenik, Gita Koshy, George Koval, Eric Lawitz, Scott Lee, Edward Loftus, Ramesh Luther, Uma Mahadevan, Peter Mannon, Roy Matsuyama, Abraham McIntosh, Gil Melmed, Kenneth Mirkin, Matthew Nichols, Benton Oubre, William Pandak, Abdulhadi Quadri, Leonard Quallich, Charles Randall, David Rausher, Miguel Regueiro, Alan Safdi, Bruce Sands, Ellen Scherl, Jason Schneier, David Schwartz, Shahriar Sedghi, Ira Shafran, Corey Siegel, Lawrence Stein, Harvey Tatum, David Weinberg, Barry Winston, Douglas Wolf, Ziad Younes, Brian G Feagan, Jean-Frédéric Colombel, Stephen Hanauer, Paul Rutgeerts, William J Sandborn, Bruce E Sands, Derek Jewell, Jeffrey Mahon, Richard Rothstein, David Snydman, Joseph Massaro, David Clifford, Joseph Berger, Eugene Major, James Provenzale, Michael Lev, Brian G Feagan, Paul Rutgeerts, Bruce E Sands, Stephen Hanauer, Jean-Frédéric Colombel, William J Sandborn, Gert Van Assche, Jeffrey Axler, Hyo-Jong Kim, Silvio Danese, Irving Fox, Catherine Milch, Serap Sankoh, Tim Wyant, Jing Xu, Asit Parikh, GEMINI 1 Study Group, Peter Bampton, Alvin Chung, Henry Debinski, Timothy Florin, David Hetzel, Ian Kronborg, Ian Lawrance, Rupert Leong, Finlay Macrae, Greg Moore, Paul Pavli, Graham Radford-Smith, Martin Weltman, Thomas Haas, Walter Reinisch, Felix Stockenhuber, Wolfgang Vogel, Marc De Maeyer, Martine De Vos, Geert D'Haens, Edouard Louis, Vinciane Muls, Gert Van Assche, Plamen Petrov, Guy Aumais, Jeffrey Axler, Alain Bitton, Raymond Bourdages, Brian Bressler, Albert Cohen, Richard Fedorak, Gordon Greenberg, Jennifer Jones, Walter Kutcher, Donald MacIntosh, Terry Ponich, Ranjit Singh, Hillary Steinhart, Richmond Sy, Ladislav Douda, Milan Lukas, Miloslav Samek, Petr Vyhnalek, Vlastimil Woznica, Zdenka Zadorova, Vibeke Andersen, Terje Rannem, Michael Staun, Anu Maelt, Benno Margus, Bruno Bonaz, Benoit Coffin, Pierre Desreumaux, David Laharie, Jean-Marie Reimund, Michael Karaus, Andrea Pace, Matthias Ross, Wolfgang Schmidt, Thomas Witthoeft, Martin Zeitz, Dimitrios Karamanolis, Gerasimos Mantzaris, Theofanis Maris, Carmen Ng, Janos Gall, Bela Hunyady, Attila Szepes, Tamas Toth, Aron Vincze, Einar Oddsson, Kjartan Örvar Jósefsspktali, Vineet Ahuja, Deepak Amarapurkar, Mahesh Goenka, Mohammed Aejaz Habeeb, Umesh Jalihal, Bharat Kalambe, Abraham Koshy, Ramesh Kumar, V G Mohan Prasad, Nageshwar Reddy, T V Sekar, Ravi Shankar, Vishwanath Tantry, Barbara Ryan, Yona Avni, Shomron Ben Horin, Sandro Ardizzone, Alessandro Armuzzi, Enrico Corazziari, Silvio Danese, Walter Fries, Anna Kohn, Diana Lisova, Abraham Mathew George, Ida Normiha Hilmi, Shashi Kumar Menon Bhaskaran, Su Yang Soon, L G J B Engels, C Y Ponsioen, Ian Wallace, John Wyeth, Jon Florholmen, Jörgen Jahnsen, Idar Lygren, Arne Röseth, Irena Ciecko-Michalska, Maciej Gonciarz, Jacek Huk, Zofia Jamrozik-Kruk, Malgorzata Kondusz-Szklarz, Leszek Paradowski, Anna Wiechowska-Kozlowska, Dong Soo Han, Sung Pil Hong, Hyo-Jong Kim, Joo Sung Kim, Kyeong Ok Kim, Young-Ho Kim, Suk-Kyun Yang, Olga Alexeeva, Elena Bunkova, Eduard Burnevich, Oleg Dolgikh, Irina Kasherininova, Yaroslava Khovaeva, Alexander Lakhin, Khoon Lin Ling, Frederik Bester, Thomas Coetzer, H de K Grundling, Leslie David Jackson, Pieter Spies, John Philip Wright, C Ziady, Esther Garcia Planella, Javier Perez Gisbert, Gerhard Rogler, Frank Seibold, Ai-Wen Kao, Deng-Chyang Wu, Ozlen Atug, Oya Ovunc Kurdas, A B Hawthorne, James Lindsay, Maria Abreu, Avanish Aggarwal, Natarajan Bala, Scott Becker, Brian Behm, Robert Braun, William Cohn, Raymond Cross, Seema Dar, Themistocles Dassopoulos, Willem De Villiers, Taddese Desta, Gerald Dryden, Aaron Duvall, Francis Farraye, Steven Fein, Blanche Fung Liu, David Gatof, Daniel Geenen, Philip Ginsburg, Sarah Glover, Vikram Gopal, Stephen Hanauer, John Hanson, Robert Hardi, Kim Isaacs, Rajesh Jain, Nicholas Karyotakis, Joshua Korzenik, Gita Koshy, George Koval, Eric Lawitz, Scott Lee, Edward Loftus, Ramesh Luther, Uma Mahadevan, Peter Mannon, Roy Matsuyama, Abraham McIntosh, Gil Melmed, Kenneth Mirkin, Matthew Nichols, Benton Oubre, William Pandak, Abdulhadi Quadri, Leonard Quallich, Charles Randall, David Rausher, Miguel Regueiro, Alan Safdi, Bruce Sands, Ellen Scherl, Jason Schneier, David Schwartz, Shahriar Sedghi, Ira Shafran, Corey Siegel, Lawrence Stein, Harvey Tatum, David Weinberg, Barry Winston, Douglas Wolf, Ziad Younes, Brian G Feagan, Jean-Frédéric Colombel, Stephen Hanauer, Paul Rutgeerts, William J Sandborn, Bruce E Sands, Derek Jewell, Jeffrey Mahon, Richard Rothstein, David Snydman, Joseph Massaro, David Clifford, Joseph Berger, Eugene Major, James Provenzale, Michael Lev
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.).
Source: PubMed