Ardizzone, Sandro
Mayo Clinic
for the INSPIRE and COMMAND Study Group
Citations 2
Risankizumab for Ulcerative Colitis
Louis, Edouard, Panaccione, Remo, Biedermann, Luc , Colombel, Jean–Frédéric, D’Haens, Geert , Hisamatsu, Tadakazu , Siegmund, Britta , Boland, Brigid S. , Melmed, Gil , Armuzzi, Alessandro , Levine, Phillip, Kalabic, Jasmina , Cheng, Ling, Shu, Lei , Duan, W. Rachel, Pivorunas, Valerie , González, Yuri Sánchez , D’Cunha, Ronilda , Neimark, Ezequiel, Wallace, Kori, Ferrante, Marc , Group, INSPIRE and COMMAND Study, Balderramo, Domingo , Goncalves, Silvina A., Lasa, Juan, Novillo, Abel, Ruffinengo, Orlando, Heeren, Sonja, Reinisch, Walter , Baert, Filip , Colard, A, Ferrante, Marc, Franchimont, Denis , Rahier, Jean‐François , Francesconi, Carlos Fernando de Magalhães , Stanchev, Desislav , Atkinson, Kenneth, Beaton, Melanie, Greenbloom, Susan, Lachance, Jean-Rene, Lim, Allen, Samson, Jean-Michel, Shulman, Scott, Siffledeen, Jesse, Alfaro, Ignacio , Valenzuela, Carlos , Walsen, Gustavo, An, Ping , Cao, Qian , Chen, Yan , Gao, Xiang , Hou, Xiaohua , Hu, Naizhong, Liu, Mei , Lungen, LU, Ran, Zhihua, Tang, Tongyu , Yang, Shaoqi , Zhan, Qiang , Zhang, Guoxin , Zhang, Xiaolan , Zhong, Jie , Zou, Xiaoping, Álvarez, Eligio, Ricaurte, Juan, Borzan, Vladimir , Puljiz, Željko , Svoboda, Pavel , Ulbrych, Jan, Vaňásek, Tomáš , Ali, Ezzat, Salem, Osama , Sawah, Hisham, Altwegg, Romain , Flamant, Mathurin, Hébuterne, Xavier , Deppe, Herbert, Klaus, Jochen , Kucharzik, Torsten , Mertens, Jessica, Mroß, Michael, Reindl, Wolfgang , Schiefke, Ingolf, Schreiber, Stefan, Sturm, Andreas , Bamias, Georgios, Manolakopoulos, Spilios , Mantzaris, Gerassimos J. , Tzouvala, Maria , Viazis, N. , Avni‐Biron, Irit , Goldin, Eran , Katz, Lior H. , Lahat-Zok, Adi, Segal, Arik, Colecchia, Antonio , Cosintino, R. , Geccherle, Andrea, Monteleone, Giovanni , Privitera, Antonino Carlo , Vangeli, Marcello, Abe, Yasuhiko , Aoyama, Nobuo , Endo, Yutaka , Esaki, Motohiro, Fujii, Toshimitsu , Fukuda, Katsuyuki , Hirai, Fumihito , Hisanaga, Yasuhiro, Horiki, Noriyuki , Iguchi, Mikitaka , Ishiguro, Yoh , Ito, Hiroaki , Kamikozuru, Koji , Kato, Jun , Kawanishi, Teruki, Kobayashi, Taku , Kuge, Hiroyuki , Masuda, Tomoyuki, Matsuoka, Katsuyoshi , Matsushima, Kayoko , Matsushima, Masashi, Motoya, Satoshi , Nakai, Katsuhiko, Nakajima, Koichi, Nakamura, Masanao, Nishida, Atsushi , Nishikawa, Takahiro , Nishimata, Nobuaki, Ochiai, Toshiaki, Ohmiya, Naoki , Ohnishi, Yoshifumi , Oka, Shiro , Ozeki, Keiji , Saito, Daisuke, Saruta, Masayuki, Sasaki, Makoto, Shimizu, Masahito , Sujino, Tomohisa , Takatori, Hajime , Takatsu, Noritaka , Tokito, Satoki, Endo, Toshiyuki, Toyokawa, Tatsuya , Uenoyama, Yoshito , Yamamoto, Takatsugu, Yasuda, Hiroshi , Yokoyama, Kaoru , Jonaitis, Laimas, Kazėnaitė, Edita, Te, Lourdes Lol-be Pinzon, Lutgens, Maurice, Brooker, James, Griffiths, Ben, Inns, Stephen , Schultz, Michael, Eszyk, Jerzy, Kleczkowski, D, Kopoń, Adam, Petryka, Robert, Romańczyk, Tomasz , Rydzewska-Wyszkowska, Grażyna , Sikorski, Piotr, Talarek, Michał, Ministro, Paula , Tavares, Helena, Diculescu, Mihai-Mircea, Goldiș, Adrian , Agafina, Alina, Edin, Anton, Gerasimova, Evgenia, Gettueva, Maryana, Кашников, В. Н. , Pirmagomedov, Albert , Rafalskiy, Vladimir , Шарапова, К. М., Varganova, Daria L , Grgov, Saša, Svorcan, Petar , Tarabar, Dino, Ling, Khoon Lin , Baláž, Jozef, Ďurina, J, Greguš, Miloš, Laclav, Martin , Deetlefs, Eduan, Peter, Jonny , Rajabally, Muhammad, Rosa, Jennifer, Zyl, JI van, Wright, John , Jang, Byung Ik , Kang, Sang-Bum, Kim, Duk-Hwan , Kim, Tae Oh , Kim, Young-Ho , Song, Geun Am , Laria, Luisa Castro, Piudo, Ana Echarri, Ramirez, Vincent Hernandez, Martín‐Arranz, María Dolores , Trastoy, Pilar Varela, Mendoza, M Vera, Lördal, Mikael, Chang, Chung-Hsin, Kuo, Chia-Jung , Lin, Ching‐Pin , Tu, Chia–Hung, Erzın, Yusuf , Soykan, İrfan , Kravchenko, Tetiana , Tsarynna, Nataliia, Vyshyvanyuk, Vira , Cummings, Fraser , Kapur, Kapil , Kaser, Arthur , Kent, Alexandra , Parkes, Gareth, Patel, Kamal , Steel, Alan , Aberra, Faten , Aguilar, Humberto , Al‐Bawardy, Badr , Barnes, Matthew D., Beck, Kendall , Berkelhammer, Charles , Bullock, Jeff, Chiplunker, Adeeti , Dalal, Robin, Dalal, Sushila , Delgado, Belkis, DiGiovanna, Michael P., Duvall, George, Freedland, Curtis, Friedenberg, Keith, Gaidos, Jill , Ginsburg, Philip, Hassanein, Tarek , Higgins, Peter , Hou, Jason K. , Huilgol, Vivek, Inamdar, Nikhil, Kapur, Saurabh, Kerman, David H., Levine, Henry, Lodhia, Nilesh, Mayoral, Jaime L., McNeil, Donald, Mushahwar, Andria M., Ojeas, Harry, Patel, Bhaktasharan, Phillips, Raymond E. , Pouzar, Joe, Sarles, H, Schock, Joel, Sedghi, Shahriar , Shah, Nirav V. , Stokesberry, David, Su, Le‐Chu, Verma, Dharmendra, Weber, John T. , Younes, Ziad , Zisman, Timothy L. , Melmed, Gil Y , Kobayashi, Taku , Siegmund, Britta , Schreiber, Stefan , Bossuyt, Peter , Parkes, Gareth, Peyrin‐Biroulet, Laurent , Wu, Kaichun , Chen, Su , Atreya, Raja Narayana , Loftus, Edward V. , Group, INSPIRE and COMMAND Study, Reinisch, Walter , Dewit, Olivier , Franchimont, Denis , Kaiser, Roberto Luiz , Parra, Rogério Serafim , Sassaki, Lígia Yukie , Пенчев, Пламен , Bessissow, Talat , Lachance, Jean-René, Panaccione, Remo , Walsen, Gustavo, Chen, Youxiang , Li, Yan , Liu, Fei , Wang, Xin , Zhan, Qiang, Zhang, Hu , Zhang, Jie , Ricaurte, Juan, Krznarić, Željko , Bortlík, Martin , Svoboda, Pavel, Kjeldsen, Jens , Munck, Lars Kristian , Poulsen, Anja, Waked, Imam A. , Fumery, Mathurin , Laharie, David , Roblin, Xavier , Tréton, Xavier , Deppe, Herbert, Hasselblatt, Peter , Kandulski, Arne , Krause, Thomas , Naumann, Axel, Schreiber, Stefan , Schubert, Stefan, Κoutroubakis, Ioannis E. , Ardizzone, Sandro , Cicala, Michele , Gasbarrini, Antonio , Giannini, Edoardo Giovanni , Gionchetti, Paolo , Luzza, Francesco , Saibeni, Simone , Abe, Yasuhiko, Asonuma, Kunio , Hisanaga, Yasuhiro, Ishigami, Keisuke, Kakuta, Yoichi , Maemoto, Atsuo , Nakajima, Koichi, Nishida, Atsushi, Sasaki, Makoto, Sugimoto, Ken , Suzuki, Takayoshi , Takedatsu, Hidetoshi , Takeuchi, Ken, Tanaka, Hiroki , Tokito, Satoki, Yamamoto, Takayuki , Derovs, Aleksejs , Puķītis, Aldis , Jonaitis, Laimas Virginijus , Gearry, Richard B. , Griffiths, Ben, Kierkuś, Jarosław , Reguła, Jarosław , Cerqueira, Rute Maria , Goncalves, Tiago, Lopes, Susana , Portela, Francisco , Seicean, Andrada , Gerasimova, Evgenia, Sharapova, Ksenia, Smolyarchuk, Е. А. , Jovanović, Igor , Balaz, Jozef, Drobne, David , Wright, John, Cheon, Jae Hee , Kim, Jee Hyun , Lee, Jong Hun , Lee, Kang‐Moon , Park, Dong Il , Argüelles‐Arias, Federico , Piudo, Ana Echarri, García‐López, Santiago , Ramirez, V Hernández, Misselwitz, Benjamin , Chou, Jen‐Wei , Tu, Chia‐Hung , Alkım, Hüseyin , Kravchenko, Tetiana, Ahmad, Tariq, Parkes, Gareth, Speight, Richard, Ananthakrishnan, Ashwin N. , Barnes, Matthew, Bullock, Jeff, DiGiovanna, Michael, Hong, John D. , Huilgol, V.R., Phillips, Raymond, Siddiqui, Junaid, Swaminath, Arun C. , Weber, John, Matsuoka, K
JAMA | July 22, 2024 | Volume: 332 | Issue: 11 | Pages: 881
Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135
IDH1‐mutated Crohn's disease‐associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated‐type dysplasia
Guerini, Camilla, Ferrario, Giuseppina , Grillo, Federica , Arpa, Giovanni , Lenti, Marco Vincenzo , Riboni, Roberta , Solcia, Enrico, Fassan, Matteo , Moens, Annick , Ferrante, Marc , Sessa, Fausto , Grillo, Federica , Lenti, Marco V , Fassan, Matteo , Vanoli, Alessandro , Furlan, Daniela , Libera, Laura , Klersy, Catherine , Mastracci, Luca , Ardizzone, Sandro , Hertogh, Gert D. , Graham, Rondell P. , Paulli, Marco , Sabatino, Antonio Di
Histopathology | November 22, 2023 | Volume: 84 | Issue: 3 | Pages: 515-524
AimsPatients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD‐SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1‐mutated CrD‐SBAs.Methods and resultsAn international multicentre series of surgically resected CrD‐SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6‐methylguanine‐DNA methyltransferase (MGMT) and long interspersed nuclear element‐1 (LINE‐1) methylation were compared between IDH1‐mutated and IDH1 wild‐type CrD‐SBAs. Ten (20%) of the 49 CrD‐SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild‐type cases, IDH1‐mutated CrD‐SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1‐mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non‐conventional subtype (two serrated dysplastic lesions and one goblet cell‐deficient dysplasia). In particular, non‐conventional serrated dysplasia was significantly associated with IDH1‐mutated CrD‐SBAs (P = 0.029). No significant cancer‐specific survival difference between IDH1‐mutated CrD‐SBA patients and IDH1 wild‐type CrD‐SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16–1.89; P = 0.313).ConclusionsIDH1‐mutated CrD‐SBAs, which represent approximately one‐fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1‐mutated non‐conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD‐SBAs.