Ryan C Ungaro1, Clara Yzet2, Peter Bossuyt3, Filip J Baert4, Thomas Vanasek5, Geert R D'Haens6, Vincent Wilhelmus Joustra6, Remo Panaccione7, Gottfried Novacek8, Walter Reinisch8, Alessandro Armuzzi9, Oleksandr Golovchenko10, Olga Prymak10, Adrian Goldis11, Simon P Travis12, Xavier Hébuterne13, Marc Ferrante14, Gerhard Rogler15, Mathurin Fumery2, Silvio Danese16, Grazyna Rydzewska17, Benjamin Pariente18, Erik Hertervig19, Carol Stanciu20, Melanie Serrero21, Mircea Diculescu22, Laurent Peyrin-Biroulet23, David Laharie24, John P Wright25, Fernando Gomollón26, Irina Gubonina27, Stefan Schreiber28, Satoshi Motoya29, Per M Hellström30, Jonas Halfvarson31, James W Butler32, Joel Petersson32, Francesca Petralia33, Jean-Frederic Colombel34. 1. Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, New York, New York. 2. Amiens University Hospital, Department of Gastroenterology, Amiens, France. 3. Imelda Gastroenterology Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden, Belgium. 4. AZ Delta Roeselare, Roeselare, Belgium. 5. Second Department of Internal Medicine, University Hospital Hradec Králové, Hradec Králové, Czech Republic. 6. Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 7. Inflammatory Bowel Disease Unit, University of Calgary, Calgary, Canada. 8. Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 9. Inflammatory Bowel Disease Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy. 10. Medical Clinical Investigational Center of Medical Center Health Clinic LLC, Vinnytsia, Ukraine. 11. Universitatea de Medicina si Farmacie, Timisoara, Romania. 12. Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, Oxford, United Kingdom. 13. Gastroenterology and Clinical Nutrition Department, Centre Hospitalier Universitaire of Nice, University of Nice Sophia-Antipolis, Nice, France. 14. University Hospitals Leuven, Leuven, Belgium. 15. Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland. 16. Humanitas University, Istituto Clinico Humanitas, Milan, Italy. 17. Central Clinical Hospital of Ministry of Interior and Administration in Warsaw, Warsaw, Poland. 18. Claude Huriez Hospital, Lille University, Lille, France. 19. Skane University Hospital, Lund, Sweden. 20. Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania. 21. Hepato-Gastroenterology Department, North Hospital, University of Mediterranean, Marseille, France. 22. University of Medicine and Pharmacy "Carol Davila," Bucharest, Romania. 23. Hépato Gastro-Entérologie, Hôpital de Brabois, Nancy, France. 24. Service d'Hépato-gastroentérologie et Oncologie Digestive, Hôpital Haut-Lévêque, Bordeaux, France. 25. Kingsbury Hospital, Cape Town, South Africa. 26. Hospital Clínico de Zaragoza, IIS Aragón, Zaragoza, Spain. 27. Military Medical Academy named after S.M. Kirov, Saint Petersburg, Russian Federation. 28. Department of Internal Medicine I, Kiel University, Kiel, Germany. 29. Inflammatory Bowel Disease Center, Sapporo Kosei General Hospital, Sapporo, Japan. 30. Uppsala University Hospital, Uppsala, Sweden. 31. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. 32. AbbVie, Inc, North Chicago, Illinois. 33. Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York. 34. Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu.
Abstract
BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scoresbelow 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS:Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.
RCT Entities:
BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALMpatient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.
Authors: Johan Burisch; Gediminas Kiudelis; Limas Kupcinskas; Hendrika Adriana Linda Kievit; Karina Winther Andersen; Vibeke Andersen; Riina Salupere; Natalia Pedersen; Jens Kjeldsen; Renata D'Incà; Daniela Valpiani; Doron Schwartz; Selwyn Odes; Jóngerð Olsen; Kári Rubek Nielsen; Zsuzsanna Vegh; Peter Laszlo Lakatos; Alina Toca; Svetlana Turcan; Konstantinos H Katsanos; Dimitrios K Christodoulou; Mathurin Fumery; Corinne Gower-Rousseau; Stefania Chetcuti Zammit; Pierre Ellul; Carl Eriksson; Jonas Halfvarson; Fernando Jose Magro; Dana Duricova; Martin Bortlik; Alberto Fernandez; Vicent Hernández; Sally Myers; Shaji Sebastian; Pia Oksanen; Pekka Collin; Adrian Goldis; Ravi Misra; Naila Arebi; Ioannis P Kaimakliotis; Inna Nikuina; Elena Belousova; Marko Brinar; Silvija Cukovic-Cavka; Ebbe Langholz; Pia Munkholm Journal: Gut Date: 2018-01-23 Impact factor: 23.059
Authors: Jean-Frederic Colombel; Remo Panaccione; Peter Bossuyt; Milan Lukas; Filip Baert; Tomas Vaňásek; Ahmet Danalioglu; Gottfried Novacek; Alessandro Armuzzi; Xavier Hébuterne; Simon Travis; Silvio Danese; Walter Reinisch; William J Sandborn; Paul Rutgeerts; Daniel Hommes; Stefan Schreiber; Ezequiel Neimark; Bidan Huang; Qian Zhou; Paloma Mendez; Joel Petersson; Kori Wallace; Anne M Robinson; Roopal B Thakkar; Geert D'Haens Journal: Lancet Date: 2017-10-31 Impact factor: 79.321
Authors: Thomas D Walters; Mi-Ok Kim; Lee A Denson; Anne M Griffiths; Marla Dubinsky; James Markowitz; Robert Baldassano; Wallace Crandall; Joel Rosh; Marian Pfefferkorn; Anthony Otley; Melvin B Heyman; Neal LeLeiko; Susan Baker; Stephen L Guthery; Jonathan Evans; David Ziring; Richard Kellermayer; Michael Stephens; David Mack; Maria Oliva-Hemker; Ashish S Patel; Barbara Kirschner; Dedrick Moulton; Stanley Cohen; Sandra Kim; Chunyan Liu; Jonah Essers; Subra Kugathasan; Jeffrey S Hyams Journal: Gastroenterology Date: 2013-10-23 Impact factor: 22.682
Authors: Jacques Cosnes; Anne Bourrier; Isabelle Nion-Larmurier; Harry Sokol; Laurent Beaugerie; Philippe Seksik Journal: Gut Date: 2012-03-02 Impact factor: 23.059
Authors: Christopher Ma; Gordon W Moran; Eric I Benchimol; Laura E Targownik; Steven J Heitman; James N Hubbard; Cynthia H Seow; Kerri L Novak; Subrata Ghosh; Remo Panaccione; Gilaad G Kaplan Journal: Am J Gastroenterol Date: 2017-10-31 Impact factor: 10.864
Authors: Remo Panaccione; Robert Löfberg; Paul Rutgeerts; William J Sandborn; Stefan Schreiber; Sofie Berg; Jen-Fue Maa; Joel Petersson; Anne M Robinson; Jean-Frederic Colombel Journal: J Crohns Colitis Date: 2019-05-27 Impact factor: 9.071
Authors: Maximilian Kutschera; Thomas Waldhör; Gottfried Novacek; Wolfgang Miehsler; Hans Peter Gröchenig; Thomas Haas; Heimo Wenzl; Pius Steiner; Robert Koch; Thomas Feichtenschlager; Gerald Eckhardt; Andreas Mayer; Andreas Kirchgatterer; Othmar Ludwiczek; Reingard Platzer; Pavol Papay; Johanna Gartner; Harry Fuchssteiner; Paul-Gerhard Peters; Gerhard Reicht; Gabriele Moser; Clemens Dejaco; Harald Vogelsang; Christian Primas Journal: United European Gastroenterol J Date: 2021-02-18 Impact factor: 4.623