. 2025 Jun;642(8067):458-466.

doi: 10.1038/s41586-025-08940-0. Epub 2025 Apr 30.

Global evolution of inflammatory bowel disease across epidemiologic stages

Lindsay Hracs^#¹, Joseph W Windsor^#¹, Julia Gorospe¹, Michael Cummings², Stephanie Coward¹, Michael J Buie¹, Joshua Quan¹, Quinn Goddard¹, Léa Caplan¹, Ante Markovinović¹, Tyler Williamson², Yvonne Abbey³, Murdani Abdullah⁴, Maria T Abreu^{5

6}, Vineet Ahuja^{6

7}, Raja Affendi Raja Ali⁸, Mansour Altuwaijri⁹, Domingo Balderramo¹⁰, Rupa Banerjee^{6

11}, Eric I Benchimol^{12

13

14

15}, Charles N Bernstein^{6

16}, Eduard Brunet-Mas^{17

18

19}, Johan Burisch^{6

20

21

22}, Vui Heng Chong²³, Iris Dotan^{6

24}, Usha Dutta²⁵, Sara El Ouali^{26

27}, Angela Forbes²⁸, Anders Forss²⁹, Richard Gearry^{6

28}, Viet Hang Dao³⁰, Juanda Leo Hartono^{31

32}, Ida Hilmi³³, Phoebe Hodges^{34

35}, Gareth-Rhys Jones³⁶, Fabián Juliao-Baños³⁷, Jamilya Kaibullayeva^{38

39}, Paul Kelly^{34

35}, Taku Kobayashi^{40

41}, Paulo Gustavo Kotze^{6

42}, Peter L Lakatos^{6

43

44}, Charlie W Lees^{45

46}, Julajak Limsrivilai⁴⁷, Bobby Lo^{20

21}, Edward V Loftus Jr^{6

48}, Jonas F Ludvigsson^{29

49}, Joyce W Y Mak⁵⁰, YingLei Miao^{51

52}, Ka Kei Ng⁵³, Shinji Okabayashi⁵⁴, Ola Olén⁵⁵, Remo Panaccione^{1

6}, Mukesh Sharma Paudel⁵⁶, Abel Botelho Quaresma^{57

58}, David T Rubin^{6

59}, Marcellus Simadibrata⁴, Yang Sun^{51

52}, Hidekazu Suzuki⁶⁰, Martin Toro⁶¹, Dan Turner^{6

62}, Beatriz Iade⁶³, Shu Chen Wei⁶⁴, Jesus K Yamamoto-Furusho⁶⁵, Suk-Kyun Yang⁶⁶, Siew C Ng^{67

68

69

70}, Gilaad G Kaplan^{71

72}; Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) Research Group

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Centre for Health Informatics and Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
³ Maidstone and Tunbridge Wells NHS Trust, Kent, UK.
⁴ Division of Gastroenterology, Department of Internal Medicine, HCRC IMERI, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
⁵ F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁶ International Organization for the study of Inflammatory Bowel Disease (IOIBD), Stockholm, Sweden.
⁷ Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
⁸ Sir Jeffrey Cheah Sunway Medical School, Faculty of Medical and Life Sciences, Sunway University, Selangor, Malaysia.
⁹ Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
¹⁰ IBD Unit, Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina.
¹¹ IBD Center, Asian Institute of Gastroenterology, Hyderabad, India.
¹² SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada.
¹³ Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹⁴ Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada.
¹⁵ ICES, Toronto, Ontario, Canada.
¹⁶ Department of Medicine, and the University of Manitoba IBD Clinical and Research Centre, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁷ Gastroenterology Department, Parc Taulí Hospital Universitari, Institut d'Investigació I Innovació Parc Taulí (I3PT-CERCA), Sabadell, Spain.
¹⁸ CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
¹⁹ Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
²⁰ Gastrounit, Medical Division, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²¹ Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²³ Division of Gastroenterology and Hepatology, Department of Medicine, Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan, Brunei Darussalam.
²⁴ Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Affiliated to the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁵ Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
²⁶ Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
²⁷ Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
²⁸ Department of Medicine, University of Otago, Christchurch, New Zealand.
²⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³⁰ Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam.
³¹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³² Division Gastroenterology & Hepatology, National University Hospital, Singapore, Singapore.
³³ Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
³⁴ Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.
³⁵ Tropical Gastroenterology & Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.
³⁶ University of Edinburgh, Institute for Regeneration and Repair, Edinburgh, UK.
³⁷ Department of Gastroenterology, Pablo Tobon Uribe Hospital, Medellín, Colombia.
³⁸ JSC Research Institute of Cardiology and Internal Diseases of the Ministry of Health of the Republic of Kazakhstan, Astana, Republic of Kazakhstan.
³⁹ Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
⁴⁰ Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
⁴¹ Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.
⁴² Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná, Curitiba, Brazil.
⁴³ Division of Gastroenterology, McGill University, Montreal, Quebec, Canada.
⁴⁴ Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.
⁴⁵ Centre for Genomics and Experimental Medicine (CGEM), Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, UK.
⁴⁶ Edinburgh IBD Unit, Western General Hospital, NHS Lothian, Edinburgh, UK.
⁴⁷ Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁴⁸ Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
⁴⁹ Department of Pediatrics, Örebro University Hospital, Stockholm, Sweden.
⁵⁰ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
⁵¹ Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
⁵² Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, China.
⁵³ Conde S. Januário Hospital, Macao SAR, China.
⁵⁴ Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵⁵ Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
⁵⁶ Department of Gastroenterology, National Academy of Medical Sciences, Kathmandu, Nepal.
⁵⁷ UNOESC Curso de Medicina: Universidade do Oeste de Santa Catarina, Joaçaba, Brazil.
⁵⁸ Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
⁵⁹ Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA.
⁶⁰ Division of Gastroenteroloy and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
⁶¹ Head of the Inflammatory Bowel Diseases Unit, HIGEA, Mendoza, Argentina.
⁶² The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, The Hebrew University of Jerusalem, Shaare Zedek Medical Center, Jerusalem, Israel.
⁶³ Cooperativa de Servicios Médicos (COSEM), Montevideo, Uruguay.
⁶⁴ Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁶⁵ Inflammatory Bowel Disease Clinic, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition and National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
⁶⁶ Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁶⁷ International Organization for the study of Inflammatory Bowel Disease (IOIBD), Stockholm, Sweden. siewchienng@cuhk.edu.hk.
⁶⁸ Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. siewchienng@cuhk.edu.hk.
⁶⁹ Microbiota I-Center (MagIC), Hong Kong, China. siewchienng@cuhk.edu.hk.
⁷⁰ New Cornerstone Science Laboratory, The Chinese University of Hong Kong, Hong Kong, China. siewchienng@cuhk.edu.hk.
⁷¹ Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. ggkaplan@ucalgary.ca.
⁷² International Organization for the study of Inflammatory Bowel Disease (IOIBD), Stockholm, Sweden. ggkaplan@ucalgary.ca.

^# Contributed equally.

PMID: 40307548
PMCID: PMC12158780
DOI: 10.1038/s41586-025-08940-0

Global evolution of inflammatory bowel disease across epidemiologic stages

Lindsay Hracs et al. Nature. 2025 Jun.

. 2025 Jun;642(8067):458-466.

doi: 10.1038/s41586-025-08940-0. Epub 2025 Apr 30.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Centre for Health Informatics and Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
³ Maidstone and Tunbridge Wells NHS Trust, Kent, UK.
⁴ Division of Gastroenterology, Department of Internal Medicine, HCRC IMERI, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
⁵ F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁶ International Organization for the study of Inflammatory Bowel Disease (IOIBD), Stockholm, Sweden.
⁷ Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
⁸ Sir Jeffrey Cheah Sunway Medical School, Faculty of Medical and Life Sciences, Sunway University, Selangor, Malaysia.
⁹ Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
¹⁰ IBD Unit, Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina.
¹¹ IBD Center, Asian Institute of Gastroenterology, Hyderabad, India.
¹² SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada.
¹³ Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹⁴ Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada.
¹⁵ ICES, Toronto, Ontario, Canada.
¹⁶ Department of Medicine, and the University of Manitoba IBD Clinical and Research Centre, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁷ Gastroenterology Department, Parc Taulí Hospital Universitari, Institut d'Investigació I Innovació Parc Taulí (I3PT-CERCA), Sabadell, Spain.
¹⁸ CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
¹⁹ Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
²⁰ Gastrounit, Medical Division, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²¹ Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²³ Division of Gastroenterology and Hepatology, Department of Medicine, Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan, Brunei Darussalam.
²⁴ Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Affiliated to the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁵ Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
²⁶ Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
²⁷ Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
²⁸ Department of Medicine, University of Otago, Christchurch, New Zealand.
²⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³⁰ Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam.
³¹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³² Division Gastroenterology & Hepatology, National University Hospital, Singapore, Singapore.
³³ Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
³⁴ Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.
³⁵ Tropical Gastroenterology & Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.
³⁶ University of Edinburgh, Institute for Regeneration and Repair, Edinburgh, UK.
³⁷ Department of Gastroenterology, Pablo Tobon Uribe Hospital, Medellín, Colombia.
³⁸ JSC Research Institute of Cardiology and Internal Diseases of the Ministry of Health of the Republic of Kazakhstan, Astana, Republic of Kazakhstan.
³⁹ Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
⁴⁰ Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
⁴¹ Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.
⁴² Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná, Curitiba, Brazil.
⁴³ Division of Gastroenterology, McGill University, Montreal, Quebec, Canada.
⁴⁴ Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.
⁴⁵ Centre for Genomics and Experimental Medicine (CGEM), Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, UK.
⁴⁶ Edinburgh IBD Unit, Western General Hospital, NHS Lothian, Edinburgh, UK.
⁴⁷ Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁴⁸ Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
⁴⁹ Department of Pediatrics, Örebro University Hospital, Stockholm, Sweden.
⁵⁰ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
⁵¹ Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
⁵² Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, China.
⁵³ Conde S. Januário Hospital, Macao SAR, China.
⁵⁴ Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵⁵ Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
⁵⁶ Department of Gastroenterology, National Academy of Medical Sciences, Kathmandu, Nepal.
⁵⁷ UNOESC Curso de Medicina: Universidade do Oeste de Santa Catarina, Joaçaba, Brazil.
⁵⁸ Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
⁵⁹ Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA.
⁶⁰ Division of Gastroenteroloy and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
⁶¹ Head of the Inflammatory Bowel Diseases Unit, HIGEA, Mendoza, Argentina.
⁶² The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, The Hebrew University of Jerusalem, Shaare Zedek Medical Center, Jerusalem, Israel.
⁶³ Cooperativa de Servicios Médicos (COSEM), Montevideo, Uruguay.
⁶⁴ Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁶⁵ Inflammatory Bowel Disease Clinic, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition and National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
⁶⁶ Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁶⁷ International Organization for the study of Inflammatory Bowel Disease (IOIBD), Stockholm, Sweden. siewchienng@cuhk.edu.hk.
⁶⁸ Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. siewchienng@cuhk.edu.hk.
⁶⁹ Microbiota I-Center (MagIC), Hong Kong, China. siewchienng@cuhk.edu.hk.
⁷⁰ New Cornerstone Science Laboratory, The Chinese University of Hong Kong, Hong Kong, China. siewchienng@cuhk.edu.hk.
⁷¹ Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. ggkaplan@ucalgary.ca.
⁷² International Organization for the study of Inflammatory Bowel Disease (IOIBD), Stockholm, Sweden. ggkaplan@ucalgary.ca.

^# Contributed equally.

PMID: 40307548
PMCID: PMC12158780
DOI: 10.1038/s41586-025-08940-0

Abstract

During the twentieth century, inflammatory bowel disease (IBD) was considered a disease of early industrialized regions in North America, Europe and Oceania¹. At the turn of the twenty-first century, IBD incidence increased in newly industrialized and emerging regions in Africa, Asia and Latin America, while the prevalence in early industrialized regions continued to grow steadily^2-4. Changes in the incidence and prevalence denote the evolution of IBD across four epidemiologic stages: stage 1 (emergence), characterized by low incidence and prevalence; stage 2 (acceleration in incidence), marked by rapidly rising incidence and low prevalence; and stage 3 (compounding prevalence), where the incidence decelerates, plateaus or declines while the prevalence steadily increases. A fourth stage (prevalence equilibrium) has been proposed in which the prevalence slope plateaus due to demographic shifts in an ageing IBD population, but it has not yet been evidenced. To date, these stages have remained theoretical, lacking specific numerical indicators to define transition points. Here, using real-world data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920-2024), we show spatiotemporal transitions across stages 1-3 and model stage 4 progression. Understanding the evolution of IBD across epidemiologic stages enables healthcare systems to better anticipate the future worldwide burden of IBD.

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Conflict of interest statement

Competing interests: M.T.A. has received research funding from the National Institute of Health, Department of Defense, The Leona M. and Harry B. Helmsley Charitable Trust (through the University of Miami), Crohn’s and Colitis Foundation and Kenneth Rainin Foundation; she is a consultant or served on advisory boards for AbbVie, Arena Pharmaceuticals (now Pfizer), Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceuticals, Janssen Global Services, Pfizer Pharmaceutical, Prometheus Biosciences, UCB Biopharma; she has received fees for lecturing from Alimentiv, Janssen Pharmaceuticals, Prime CME and WebMD Global LLC. D.B. has received speaking fees from AbbVie, Takeda and Janssen, and consulting fees from AbbVie, Takeda, Janssen and Amgen. R.B. has received grants/research support from the Asian Healthcare Foundation, Pfizer Global, Indian council of Medical Research (ICMR) and the Leona M and Harry B Helmsley Charitable Trust; and advisory board fees from Abbott, AstraZeneca, Cadila, Cipla, Celltrion, Dr Reddy Labs, Emcure, Ferring Pharmaceuticals, Hetero Drugs, Janssen, La Renon, MSN Labs, Mankind Pharma, Menarini, Micro Labs, Nestle, Pfizer, RPG Lifesciences, Sun Pharmaceuticals, Systopic, Takeda Pharmaceuticals, Torrent, Waterley and Zydus. E.I.B. has acted as a consultant for McKesson Canada and the Dairy Farmers of Ontario for matters unrelated to medications used to treat IBD; he has also acted as a consultant for the Canadian Agency for Drugs and Technology in Health (CADTH). C.N.B. is supported by the Bingham Chair in Gastroenterology; has served on advisory boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly Canada, JAMP Pharmaceuticals, Janssen Canada, Pendopharm Canada, Sandoz Canada, Takeda Canada and Pfizer Canada; Consultant for Takeda; Educational grants from AbbVie Canada, Bristol Myers Squibb Canada, Ferring Canada, Pfizer Canada, Takeda Canada, Janssen Canada, Organon Canada, Eli Lilly Canada and Amgen Canada; speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Sandoz Canada, Takeda Canada and Pfizer Canada. E.B.-M. has served as a speaker and consultant for Janssen, Chiesi, Takeda and Kern. J.B. reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring and personal fees from Galapagos; outside the submitted work. I.D. received consultation fees/served in advisory boards/speakers’ bureaus for AbbVie, Athos, Arena, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Food Industries Organization, Gilead, Galapagos, Iterative Scopes, Janssen, Neopharm, Pfizer, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda, Wildbio and Prometheus. Jill Roberts IBD Center, shareholder: Gutreat, Harp diagnostics. S.E.O. has received honoraria for speaking from AbbVie and Janssen. A. Forss has served as a speaker and advisory board member for Janssen and Tillotts Pharma. R.G. has received research funding from AbbVie, Janssen, Zespri, Comvita, Goodman Fielder and Takeda; he has served on advisory boards for AbbVie, Janssen, Zespri, Comvita and Takeda; and has received honoraria from AbbVie, Janssen, Zespri and Takeda. J.L.H. has received consultation and speaking fee from Janssen, Ferring, AbbVie and Takeda. I.H. has received consulting and speaking honoraria from AbbVie, Janssen, Ferring, LF Asia, Pfizer and Takeda. B.I. has been member of advisory boards for AbbVie, Janssen and Takeda. G.-R.J. is funded by a Wellcome Trust Clinical Research Career Development Fellowship and has received speaker fees from AbbVie, Ferring Pharmaceuticals, Janssen, Takeda, Fresenius Kabi and Pfizer. F.J.-B. has received consulting and speaking fees from AbbVie, Janssen, Pfizer, Celltrion and Takeda. J.K. has served on advisory boards for Janssen Kazakhstan and has been a consultant for Takeda and Ferring; has been on speaker panels for Janssen, Takeda, Ferring, Thermo Fisher Scientific; and has received research funding from Ferring Kazakhstan. G.G.K. has received honoraria for speaking or consultancy from AbbVie, Amgen, Janssen, Pfizer, Sandoz and Pendophram; received grants for research from Ferring and for educational activities from AbbVie, Bristol Myers Squibb, Ferring, Fresenius-Kabi, Janssen, Pfizer, Takeda; he shares ownership of a patent: Treatment of inflammatory disorders, autoimmune disease and PBC; UTI Limited Partnership, assignee; patent WO2019046959A1, PCT/CA2018/051098; 7 September 2018. T.K. has served as an advisory board member, consultant or speaker for AbbVie, Activaid, Ajinomoto Bio-Pharma, Alfresa Pharma, Alimentiv, Astellas Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, JMDC, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical, and has received research funding from AbbVie, Alfresa Pharma, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical. P.G.K. has received consulting and speaking honorarium from AbbVie, Janssen, Pfizer and Takeda. He also has received scientific grants from Pfizer and Takeda. P.L.L. has been a speaker and/or advisory board member for AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genetech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Sandoz, Takeda, Tillots and Viatris; and has received unrestricted research grants from AbbVie, Gilead, Takeda and Pfizer. C.W.L. is funded by a UK Research and Innovation Future Leaders Fellowship and has acted as a speaker and/or consultant to AbbVie, Janssen, Takeda, Pfizer, Galapagos, GSK, Gilead, Vifor Pharma, Ferring, Dr Falk, BMS, Boehringer Ingelheim, Novartis, Sandoz, Celltrion, Cellgene, Amgen, Samsung Bioepis, Fresenius Kabi, Tillotts, Trellus Health and Iterative Health. B.L. has received speaking fees from Tillotts Pharma and Janssen Cilag; consultancy fees from Tillotts Pharma and Bristol Myers Squib; and has received unrestricted research grants from Janssen Cilag, Tillotts Pharma; outside the submitted work. E.V.L. has consulted for AbbVie, Alvotech, Amgen, Arena, Astellas, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota Biosciences, Iterative Health, Janssen, Morphic, Ono, Protagonist, Sun, Surrozen, Takeda, TR1X and UCB; has received research support from AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Takeda, Theravance and UCB; and is a shareowner of Exact Sciences. S.C.N. has served as an advisory board member for Pfizer, Ferring, Janssen and AbbVie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie and Takeda; has received research grants through her affiliated institutions from Olympus, Ferring and AbbVie; is a founder member, non-executive director, non-executive scientific advisor and shareholder of GenieBiome Ltd; and receives patent royalties through her affiliated institutions. S.O. has received speaking fees from Mitsubishi Tanabe Pharma and consulting fees from EA Pharma. O.O. has been PI on projects at Karolinska Institutet partly financed by investigator-initiated grants from Janssen, Takeda, AbbVie, Pfizer, Bristoll Myers Squibb and Ferring, and also report grants from Pfizer, AbbVie, Janssen and Galapagos in the context of a national safety monitoring programs; none of these studies have any relation to the present study. The Karolinska Institutet has received fees for lectures and participation on advisory boards by O.O. from Janssen, Ferring, Takeda and Pfizer on topics not related to the present study. R.P. has received consulting fees from Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics and Takeda. A.B.Q. has received speaking honorarium from AbbVie, Apsen and Janssen. R.A.R.A. has received speaking and consulting honoraria from AbbVie, Astra Zeneca, Ferring, Pfizer, Janssen and Takeda. D.T.R. has received grant support from Takeda; and has served as a consultant for AbbVie, Altrubio, Abivax SA, Altrubio, Avalo Therapeutics, Bausch Health, Bristol-Myers Squibb, Buhlmann Diagnostics, ClostraBio, Connect BioPharma, Douglas Pharmaceuticals, Eli Lilly, Genentech, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Odyssey Therapeutics, Pfizer, Sanofi and Takeda Pharmaceuticals; he serves on the board of trustees for the Crohn’s & Colitis Foundation and is on the board of directors for Cornerstones Health. H.S. has received honoraria for speaking from Astellas, AbbVie, Biofermin, EA Pharma, Janssen, Kissei, Miyarisan, Otsuka, Tanabe-Mitsubishi, Takeda, Tsumura and Viatris; and received grants for research from Toh-so and Biofermin. M.T. has received consulting and speaking fees from AbbVie, Janssen and Takeda. D.T. received consultation fees, research grants, royalties or honoraria from Janssen, Pfizer, Shaare Zedek Medical Center, Hospital for Sick Children, Ferring, AbbVie, Takeda, Prometheus Biosciences, Lilly, Roche, Thermo Fisher Scientific, BMS and SorrisoPharma. S.C.W. has received consultancy fees from AbbVie, Bristol-Myers Squibb, Celltrion, Ferring Pharmaceuticals, Janssen, Pfizer, Takeda and Tanabe, and speaker fees from AbbVie, Bristol-Myers Squibb, Celltrion, Excelsior Biopharma, Ferring Pharmaceuticals, Pfizer, Janssen, Sanofi, Takeda and Tanabe. T.W. received funding for educational activities from AbbVie and Pfizer. J.K.Y.-F. is a speaker bureau member for AbbVie, Alfasigma, Asofarma, Bristol Myers Squibb, Carnot, Celltrion, Chinoin, Farmasa, Ferring, Janssen, Siegfried Rhein and Takeda; is a clinical research investigator Bristol Myers Squibb and Takeda; has been member of advisory boards for AbbVie, Celltrion, Ferring, Janssen and Takeda; has received research grants from Takeda; received payments for lectures from AbbVie, Alfasigma, Asofarma, Bristol Myers Squibb, Carnot, Celltrion, Chinoin, Farmasa, Ferring, Janssen, Siegfried Rhein and Takeda; and is an advisory board member of the AbbVie, Celltrion, Ferring, Janssen and Takeda. The other authors declare no competing interests.

Figures

**Fig. 1. The incidence (per 100,000 person-years) and prevalence (per 100,000) of IBD by decade and region.**
a, The incidence of CD by decade, with regions ranked from the highest (top) to lowest (bottom) most recent median incidence value available. b, The incidence of UC by decade, with regions ranked from the highest (top) to lowest (bottom) most recent median incidence value available. c, The prevalence of CD by decade, with regions ranked from the highest (top) to lowest (bottom) most recent median prevalence value available. d, The prevalence of UC by decade, with regions ranked from the highest (top) to lowest (bottom) most recent median prevalence value available. Colour saturation represents median incidence/prevalence, calculated from all studies within a given region for that decade. CR values (25th to 75th percentiles) of incidence/prevalence for the corresponding region–decade pairing are provided in Supplementary Fig. 2. All data are available at Figshare (10.6084/m9.figshare.24952557). An interactive map depicting year-over-year changes in incidence and prevalence is available online (https://kaplan-gi.shinyapps.io/GIVES21/). Regions are labelled with their International Organization for Standardization (ISO) 3166-1 alpha-3 codes: Algeria (DZA), Argentina (ARG), Australia (AUS), Austria (AUT), Bahrain (BHR), Barbados (BRB), Belgium (BEL), Bosnia and Herzegovina (BIH), Brazil (BRA), Brunei (BRN), Canada (CAN), China (CHN), Colombia (COL), Croatia (HRV), Cyprus (CYP), Czechia (CZE), Denmark (DNK), Estonia (EST), Faroe Islands (FRO), Finland (FIN), France (FRA), Germany (DEU), Greece (GRC), Greenland (GRL), Guadeloupe and Martinique (GLP and MTQ), Hong Kong (HKG), Hungary (HUN), Iceland (ISL), India (IND), Indonesia (IDN), Iran (IRN), Ireland (IRL), Israel (ISR), Italy (ITA), Japan (JPN), Kazakhstan (KAZ), Kuwait (KWT), Lebanon (LBN), Lithuania (LTU), Macao (MAC), Malaysia (MYS), Mexico (MEX), Moldova (MDA), Netherlands (NLD), New Zealand (NZL), Norway (NOR), Oman (OMN), Panama (PAN), Philippines (PHL), Poland (POL), Portugal (PRT), Puerto Rico (PRI), Romania (ROU), Russia (RUS), San Marino (SMR), Saudi Arabia (SAU), Serbia (SRB), Singapore (SGP), Slovakia (SVK), South Africa (ZAF), South Korea (KOR), Spain (ESP), Sri Lanka (LKA), Sweden (SWE), Switzerland (CHE), Taiwan (TWN), Tanzania (TZA), Thailand (THA), Türkiye (TUR), United Kingdom (GBR), United States of America (USA) and Uruguay (URY). Regions with ISO 3166-2 codes are as follows: Catalonia (ES-CT), England (GB-ENG), Northern Ireland (GB-NIR), Scotland (GB-SCT) and Wales (GB-WLS).

**Fig. 2. CRs of CD and UC across epidemiologic stages 1, 2 and 3.**
a, The CR-I of CD (left) and UC (right) across the three epidemiologic stages. Number of observations: n = 263 (CD stage 1), n = 1,011 (CD stage 2), n = 796 (CD stage 3), n = 277 (UC stage 1), n = 847 (UC stage 2), n = 760 (UC stage 3). b, The CR-P of CD (left) and UC (right) across the three epidemiologic stages. Number of observations: n = 86 (CD stage 1), n = 247 (CD stage 2), n = 443 (CD stage 3), n = 118 (UC stage 1), n = 238 (UC stage 2), n = 435 (UC stage 3). Data are categorized by type (incidence/prevalence), disease type (CD/UC) and epidemiologic stage (stage 1, stage 2, stage 3), as determined by the random-forest classifier. For the box plots, the centre line shows the median, the lower hinge shows the 25th percentile (that is, first quartile) and the upper hinge shows the 75th percentile (that is, third quartile). The 25th and 75th percentiles are labelled and correspond to the CRs. Statistical analysis was performed using negative binomial regression with post hoc comparisons of estimated marginal means with Tukey adjustment for multiple comparisons, showing significant differences between all stages for the incidence and prevalence of CD and UC (P < 0.001 for all comparisons).

**Fig. 3. Global maps depicting epidemiologic stages of IBD evolution from 1950 to 2024.**
a, Epidemiologic stages from 1950 to 1959. b, Epidemiologic stages from 1960 to 1969. c, Epidemiologic stages from 1970 to 1979. d, Epidemiologic stages from 1980 to 1989. e, Epidemiologic stages from 1990 to 1999. f, Epidemiologic stages from 2000 to 2009. g, Epidemiologic stages from 2010 to 2019. h, Epidemiologic stages from 2020 to 2024; because regions cannot regress in stage, regions without data in 2020–2024 but with a previous stage 3 classification are shaded in a lighter green than regions in stage 3 that do have data during this period. Each region is coloured according to its epidemiologic stage as predicted by the random-forest classifier. Interactive maps are available online (https://kaplan-gi.shinyapps.io/GIVES21/).

**Fig. 4. PDE-modelled time-dependent prevalence.**
a, Modelled time-dependent prevalence of IBD in Canada (observed data, 2007–2014), Denmark (observed data, 2010–2017) and Scotland (observed data, 2010–2017). b, Central difference approximations of the slopes of time-dependent IBD prevalence.

**Fig. 5. Calculations of IBD prevalence over time under scenarios of incidence rate change.**
a, The prevalence in Canada under a 2%, 1%, 0%, −1% and −2% change in incidence per year, with the base incidence rate set equal to the average incidence from 2007 to 2014. b, The prevalence in Denmark under a 2%, 1%, 0%, −1% and −2% change in incidence per year, with the base incidence rate set equal to the average incidence from 2010 to 2017. c, The prevalence in Scotland under a 2%, 1%, 0%, −1% and −2% change in incidence per year, with the base incidence rate set equal to the average incidence from 2010 to 2017. d, Central difference approximations of the slopes of the time-dependent prevalence in Canada for each of the five yearly incidence rate change scenarios. e, Central difference approximations of the slopes of the time-dependent prevalence in Denmark for each of the five yearly incidence rate change scenarios. f, Central difference approximations of the slopes of the time-dependent prevalence in Scotland for each of the five yearly incidence rate change scenarios.

**Extended Data Fig. 1. Density of all incidence data included in the systematic review for Crohn’s disease and ulcerative colitis across regions and time.**
All data are represented in violin plots with boxplot overlays where the middle line on the boxplot is the median, the lower hinge on the boxplot is the 25^th percentile (i.e., first quartile), the upper hinge on the boxplot is the 75^th percentile (i.e., third quartile); the violin is the data density at the associated value on the y-axis, and points are individual data points outside of the density distribution. Incidence rates of Crohn’s disease or ulcerative colitis that exceed the ceiling threshold of 40 per 100,000 are considered outlier data.

**Extended Data Fig. 2. Annual incidence and prevalence of Crohn’s disease and ulcerative across epidemiologic stages of IBD evolution.**
a, Annual incidence of Crohn’s disease categorized by three epidemiologic stages of IBD evolution as predicted by the random forest classifier. b, Annual incidence of ulcerative colitis categorized by three epidemiologic stages of IBD evolution as predicted by the random forest classifier. c, Annual prevalence of Crohn’s disease categorized by three epidemiologic stages of IBD evolution as predicted by the random forest classifier. d, Annual prevalence of ulcerative colitis categorized by three epidemiologic stages of IBD evolution as predicted by the random forest classifier. Each point corresponds to an annual aggregate mean of CD or UC incidence/prevalence for all regions with available data.

**Extended Data Fig. 3. Comparison of societal indicators across three epidemiologic stages.**
a, Augmented Human Development Index (AHDI) stratified by epidemiologic stage, as predicted by the random forest classifier (number of observations: stage 1 n = 470; stage 2 n = 1,090; stage 3 n = 540). b, Obesity rate stratified by epidemiologic stage, as predicted by the random forest classifier (number of observations: stage 1 n = 295; stage 2 n = 791; stage 3 n = 476). c, Universal Health Coverage (UHC) Service Index stratified by epidemiologic stage, as predicted by the random forest classifier (number of observations: stage 1 n = 160; stage 2 n = 400; stage 3 n = 380). d, Percent urbanization stratified by epidemiologic stage, as predicted by the random forest classifier (number of observations: stage 1 n = 460; stage 2 n = 1,180; stage 3 n = 610). e, Western Diet Index (WDI) stratified by epidemiologic stage, as predicted by the random forest classifier (number of observations: stage 1 n = 348; stage 2 n = 980; stage 3 n = 540). All data are represented in boxplots where the middle line is the median, the lower hinge is the 25^th percentile (i.e., first quartile), the upper hinge is the 75^th percentile (i.e., third quartile), the lower whisker extends to 1.5 × the interquartile range (IQR) from the first quartile, the upper whisker extends to 1.5 × IQR from the third quartile, and the data points beyond the end of the whiskers are individually plotted outliers. A Kruskal-Wallis non-parametric test with *post hoc* comparisons using Wilcoxon rank-sum adjusted for multiple comparisons showed significant differences between epidemiologic stages for AHDI, obesity rate, UHC Service Index, percent urbanization, and Western Diet Index (p < 0.001 for all comparisons).

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References

1. Kaplan, G. G. The global burden of IBD: from 2015 to 2025. Nat. Rev. Gastroenterol. Hepatol.12, 720–727 (2015). - PubMed
1. Kaplan, G. G. & Windsor, J. W. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol.18, 56–66 (2021). - PMC - PubMed
1. Molodecky, N. A. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology142, 46–54 (2012). - PubMed
1. Ng, S. C. et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet390, 2769–2778 (2017). - PubMed
1. Kaplan, G. G. & Ng, S. C. Globalisation of inflammatory bowel disease: perspectives from the evolution of inflammatory bowel disease in the UK and China. Lancet Gastroenterol. Hepatol.1, 307–316 (2016). - PubMed

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Global evolution of inflammatory bowel disease across epidemiologic stages

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Global evolution of inflammatory bowel disease across epidemiologic stages

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