The Global Evolution of Inflammatory Bowel Disease across Four Epidemiologic Stages

The Global Evolution of Inflammatory Bowel Disease across Four Epidemiologic Stages | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article The Global Evolution of Inflammatory Bowel Disease across Four Epidemiologic Stages Gilaad Kaplan, Lindsay Hracs, Joseph Windsor, Julia Gorospe, Michael Cummings, and 61 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3846147/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract During the 20th century, inflammatory bowel disease (IBD) was considered a disease of early-industrialized regions in North America, Europe, and Oceania. At the turn of the 21st century, incidence of IBD increased in newly-industrialized and emerging regions in Africa, Asia, and Latin America, while prevalence in early-industrialized regions started to grow steadily. Changes in incidence and prevalence denote evolution of IBD across four epidemiologic stages: Stage 1 (Emergence), characterized by low incidence and prevalence; stage 2 (Acceleration in Incidence), characterized by rapidly rising incidence and low prevalence; and stage 3 (Compounding Prevalence), characterized by decelerating, plateauing, or declining incidence and steadily rising prevalence. A fourth stage (Prevalence Equilibrium) has been proposed where the slope of prevalence plateaus due to shifting demographics of an aging IBD population, but it has not yet been evidenced. To date, these stages have been theoretical without specific incidence/prevalence indicators defining transition points. Using real-world data from 490 population-based studies comprising 80 global regions and spanning over a century (1920–2023), we show spatiotemporal transitions across stages 1–3 and model transition towards stage 4. Understanding the evolution of IBD across epidemiologic stages allows healthcare systems to better prepare for the future worldwide burden of IBD. Health sciences/Diseases/Gastrointestinal diseases/Inflammatory bowel disease Health sciences/Medical research/Epidemiology Full Text Additional Declarations Yes there is potential Competing Interest. The authors declare the following competing interests: Dr. Abreu 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 Inc, Arena Pharmaceuticals Inc (now Pfizer), Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences Inc, Janssen Pharmaceuticals, Janssen Global Services, Pfizer Pharmaceutical, Prometheus Biosciences, UCB Biopharma SRL. She has received fees for lecturing from Alimentiv, Janssen Pharmaceuticals, Prime CME, and WebMD Global LLC. Dr. Balderramo has received speaking fees from AbbVie, Takeda and Janssen, and consulting fees from AbbVie, Takeda, Janssen and Amgen. Dr. Benchimol has acted as a consultant for McKesson Canada and the Dairy Farmers of Ontario for matters unrelated to medications used to treat inflammatory bowel disease. He has also acted as a consultant for the Canadian Agency for Drugs and Technology in Health (CADTH). Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. Dr. Bernstein 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. Dr. Brunet-Mas has served as a speaker and consultant for Janssen, Chiesi, Takeda and Kern. Dr. Burisch 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. Dr. Dotan 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. Dr. El Ouali has received honoraria for speaking from AbbVie and Janssen. Dr. Forss has served as a speaker and advisory board member for Janssen corporation and Tillotts Pharma. Dr. Gearry 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. Dr. Hartono has received consultation and speaking fee from Janssen, Ferring, AbbVie, and Takeda. Dr. Hilmi has received consulting and speaking honoraria from AbbVie, Janssen, Ferring, LF Asia, Pfizer, and Takeda. Dr. Jones 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. Dr. Juliao-Baños has received consulting and speaking fees from AbbVie, Janssen, Pfizer, Celltrion, and Takeda. Dr. Kaibullayeva 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. Dr. Kaplan has received honoraria for speaking or consultancy from AbbVie, Amgen, Janssen, Pfizer, Sandoz, and Pendophram. Dr. Kaplan 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 Sept. 2018. Dr. Kobayashi 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. Dr. Kotze has received consulting and speaking honorarium from AbbVie, Janssen, Pfizer and Takeda. He also has received scientific grants from Pfizer and Takeda. Dr. Lakatos has been a speaker and/or advisory board member: 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 grant: AbbVie, Gilead, Takeda, and Pfizer. Professor Lees 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. Dr. Lo has received speaking fees from Tillotts Pharma and Janssen Cilag; consultancy fee from Tillotts Pharma and Bristol Myers Squib; and received unrestricted research grants from Janssen Cilag, Tillotts Pharma; outside the submitted work. Professor Loftus 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. Dr. Siew Ng 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. She has received research grants through her affiliated institutions from Olympus, Ferring, and AbbVie. Siew Ng is a founder member, non-executive director, non-executive scientific advisor, and shareholder of GenieBiome Ltd. Siew Ng receives patent royalties through her affiliated institutions. Dr. Okabayashi has received speaking fees from Mitsubishi Tanabe Pharma and consulting fees from EA Pharma. Dr. Olén 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. Karolinska Institutet has received fees for lectures and participation on advisory boards by Dr. Olén from Janssen, Ferring, Takeda, and Pfizer on topics not related to the present study. Dr. Panaccione 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, Takeda. Dr. Quaresma has received speaking honorarium from AbbVie, Apsen and Janssen. Dr. Raja Ali has received speaking and consulting honoraria from AbbVie, Astra Zeneca, Ferring, Pfizer, Janssen and Takeda. Dr. Rubin has received grant support from Takeda; and has served as a consultant for AbbVie, Altrubio, Amgen, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health. Dr. Suzuki has received honoraria for speaking from Astellas, AbbVie, Biofermin, EA Pharma, Janssen, Kissei, Miyarisan, Otsuka, Tanabe-Mitsubishi, Takeda, Tsumura, and Viatris. Dr. Suzuki received grants for research from Toh-so and Biofermin. Dr. Toro has received consulting and speaking fees from AbbVie, Janssen, and Takeda. Dr. Turner 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, ThermoFisher, BMS, SorrisoPharma. Dr. Vergara has been member of advisory boards for AbbVie, Janssen, and Takeda. Dr. Wei has received consultancy fees from AbbVie, Bristol-Myers Squibb, Celltrion, Ferring Pharmaceuticals Inc., Janssen, Pfizer Inc, Takeda, and Tanabe, and speaker fees from AbbVie, Bristol-Myers Squibb, Celltrion, Excelsior Biopharma Inc., Ferring Pharmaceuticals Inc., Pfizer Inc, Janssen, Sanofi, Takeda and Tanabe. Dr. Yamamoto-Furusho is a speaker bureau member for AbbVie, Alfasigma, Asofarma, Bristol Myers Squibb, Carnot, Celltrion, Chinoin, Farmasa, Ferring, Janssen, Siegfried Rhein, Takeda; is a clinical research investigator Bristol Myers Squibb, Takeda has been member of advisory boards for AbbVie, Celltrion, Ferring, Janssen, Takeda; has received research grants from Takeda; payments for lectures from AbbVie, Alfasigma, Asofarma, Bristol Myers Squibb, Carnot, Celltrion, Chinoin, Farmasa, Ferring, Janssen, Siegfried Rhein, Takeda; and is an advisory board member of the AbbVie, Celltrion, Ferring, Janssen, Takeda. No competing interests: Dr. Yvonne Abbey, Dr. Murdani Abdullah, Dr. Vineet Ahuja, Dr. Mansour Altuwaijri, Dr. Rupa Banerjee, Michael Buie, Léa Caplan, Dr. Vui Heng Chong, Dr. Stephanie Coward, Dr. Michael Cummings, Dr. Viet Hang Dao, Dr. Usha Dutta, Angela Forbes, Quinn Goddard, Julia Gorospe, Dr. Phoebe Hodges, Dr. Lindsay Hracs, Dr. Paul Kelly, Dr. Julajak Limsrivilai, Dr. Jonas F. Ludvigsson, Dr. Joyce WY Mak, Ante Markovinović , Dr. YingLei Miao, Dr. Ka Kei Ng, Dr. Mukesh Sharma Paudel, Joshua Quan, Dr. Marcellus Simadibrata, Dr. Yang Sun, Dr. Tyler Williamson, Dr. Joseph W. Windsor, and Dr. Suk-Kyun Yang. Supplementary Files SupplementaryInformationJan42024SUBMIT.pdf Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3846147","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":266190809,"identity":"b2cfcc4d-e6ce-4a21-bf6f-02bbb62b11ba","order_by":0,"name":"Gilaad 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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 Inc, Arena Pharmaceuticals Inc (now Pfizer), Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences Inc, Janssen Pharmaceuticals, Janssen Global Services, Pfizer Pharmaceutical, Prometheus Biosciences, UCB Biopharma SRL. She has received fees for lecturing from Alimentiv, Janssen Pharmaceuticals, Prime CME, and WebMD Global LLC.\r\n\r\nDr. Balderramo has received speaking fees from AbbVie, Takeda and Janssen, and consulting fees from AbbVie, Takeda, Janssen and Amgen.\r\n\r\nDr. Benchimol has acted as a consultant for McKesson Canada and the Dairy Farmers of Ontario for matters unrelated to medications used to treat inflammatory bowel disease. He has also acted as a consultant for the Canadian Agency for Drugs and Technology in Health (CADTH).\r\n\r\nDr. Bernstein is supported by the Bingham Chair in Gastroenterology. Dr. Bernstein 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.\r\n\r\nDr. Brunet-Mas has served as a speaker and consultant for Janssen, Chiesi, Takeda and Kern.\r\n\r\nDr. Burisch 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.\r\n\r\nDr. Dotan 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.\r\n\r\nDr. El Ouali has received honoraria for speaking from AbbVie and Janssen.\r\n\r\nDr. Forss has served as a speaker and advisory board member for Janssen corporation and Tillotts Pharma.\r\n\r\nDr. Gearry 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.\r\n\r\nDr. Hartono has received consultation and speaking fee from Janssen, Ferring, AbbVie, and Takeda.\r\n\r\nDr. Hilmi has received consulting and speaking honoraria from AbbVie, Janssen, Ferring, LF Asia, Pfizer, and Takeda.\r\n\r\nDr. Jones 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. \r\n\r\nDr. Juliao-Baños has received consulting and speaking fees from AbbVie, Janssen, Pfizer, Celltrion, and Takeda.\r\n\r\nDr. Kaibullayeva 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.\r\n\r\nDr. Kaplan has received honoraria for speaking or consultancy from AbbVie, Amgen, Janssen, Pfizer, Sandoz, and Pendophram. Dr. Kaplan 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 Sept. 2018.\r\n\r\nDr. Kobayashi 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.\r\n\r\nDr. Kotze has received consulting and speaking honorarium from AbbVie, Janssen, Pfizer and Takeda. He also has received scientific grants from Pfizer and Takeda.\r\n\r\nDr. Lakatos has been a speaker and/or advisory board member: 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 grant: AbbVie, Gilead, Takeda, and Pfizer.\r\n\r\nProfessor Lees 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.\r\n\r\nDr. Lo has received speaking fees from Tillotts Pharma and Janssen Cilag; consultancy fee from Tillotts Pharma and Bristol Myers Squib; and received unrestricted research grants from Janssen Cilag, Tillotts Pharma; outside the submitted work.\r\n\r\nProfessor Loftus 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.\r\n\r\nDr. Siew Ng 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. She has received research grants through her affiliated institutions from Olympus, Ferring, and AbbVie. Siew Ng is a founder member, non-executive director, non-executive scientific advisor, and shareholder of GenieBiome Ltd. Siew Ng receives patent royalties through her affiliated institutions. \r\n\r\nDr. Okabayashi has received speaking fees from Mitsubishi Tanabe Pharma and consulting fees from EA Pharma.\r\n\r\nDr. Olén 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. Karolinska Institutet has received fees for lectures and participation on advisory boards by Dr. Olén from Janssen, Ferring, Takeda, and Pfizer on topics not related to the present study.\r\n\r\nDr. Panaccione 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, Takeda.\r\n\r\nDr. Quaresma has received speaking honorarium from AbbVie, Apsen and Janssen.\r\n\r\nDr. Raja Ali has received speaking and consulting honoraria from AbbVie, Astra Zeneca, Ferring, Pfizer, Janssen and Takeda.\r\n\r\nDr. Rubin has received grant support from Takeda; and has served as a consultant for AbbVie, Altrubio, Amgen, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health. \r\n\r\nDr. Suzuki has received honoraria for speaking from Astellas, AbbVie, Biofermin, EA Pharma, Janssen, Kissei, Miyarisan, Otsuka, Tanabe-Mitsubishi, Takeda, Tsumura, and Viatris. Dr. Suzuki received grants for research from Toh-so and Biofermin.\r\n\r\nDr. Toro has received consulting and speaking fees from AbbVie, Janssen, and Takeda.\r\n\r\nDr. Turner 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, ThermoFisher, BMS, SorrisoPharma.\r\n\r\nDr. Vergara has been member of advisory boards for AbbVie, Janssen, and Takeda.\r\n\r\nDr. Wei has received consultancy fees from AbbVie, Bristol-Myers Squibb, Celltrion, Ferring Pharmaceuticals Inc., Janssen, Pfizer Inc, Takeda, and Tanabe, and speaker fees from AbbVie, Bristol-Myers Squibb, Celltrion, Excelsior Biopharma Inc., Ferring Pharmaceuticals Inc., Pfizer Inc, Janssen, Sanofi, Takeda and Tanabe.\r\n\r\nDr. Yamamoto-Furusho is a speaker bureau member for AbbVie, Alfasigma, Asofarma, Bristol Myers Squibb, Carnot, Celltrion, Chinoin, Farmasa, Ferring, Janssen, Siegfried Rhein, Takeda; is a clinical research investigator Bristol Myers Squibb, Takeda has been member of advisory boards for AbbVie, Celltrion, Ferring, Janssen, Takeda; has received research grants from Takeda; payments for lectures from AbbVie, Alfasigma, Asofarma, Bristol Myers Squibb, Carnot, Celltrion, Chinoin, Farmasa, Ferring, Janssen, Siegfried Rhein, Takeda; and is an advisory board member of the AbbVie, Celltrion, Ferring, Janssen, Takeda.\r\n\r\nNo competing interests: Dr. Yvonne Abbey, Dr. Murdani Abdullah, Dr. Vineet Ahuja, Dr. Mansour Altuwaijri, Dr. Rupa Banerjee, Michael Buie, Léa Caplan, Dr. Vui Heng Chong, Dr. Stephanie Coward, Dr. Michael Cummings, Dr. Viet Hang Dao, Dr. Usha Dutta, Angela Forbes, Quinn Goddard, Julia Gorospe, Dr. Phoebe Hodges, Dr. Lindsay Hracs, Dr. Paul Kelly, Dr. Julajak Limsrivilai, Dr. Jonas F. Ludvigsson, Dr. Joyce WY Mak, Ante Markovinović , Dr. YingLei Miao, Dr. Ka Kei Ng, Dr. Mukesh Sharma Paudel, Joshua Quan, Dr. Marcellus Simadibrata, Dr. Yang Sun, Dr. Tyler Williamson, Dr. Joseph W. Windsor, and Dr. Suk-Kyun Yang.","formattedTitle":"The Global Evolution of Inflammatory Bowel Disease across Four Epidemiologic Stages","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3846147/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3846147/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"During the 20th century, inflammatory bowel disease (IBD) was considered a disease of early-industrialized regions in North America, Europe, and Oceania. At the turn of the 21st century, incidence of IBD increased in newly-industrialized and emerging regions in Africa, Asia, and Latin America, while prevalence in early-industrialized regions started to grow steadily. Changes in incidence and prevalence denote evolution of IBD across four epidemiologic stages: Stage 1 (Emergence), characterized by low incidence and prevalence; stage 2 (Acceleration in Incidence), characterized by rapidly rising incidence and low prevalence; and stage 3 (Compounding Prevalence), characterized by decelerating, plateauing, or declining incidence and steadily rising prevalence. A fourth stage (Prevalence Equilibrium) has been proposed where the slope of prevalence plateaus due to shifting demographics of an aging IBD population, but it has not yet been evidenced. To date, these stages have been theoretical without specific incidence/prevalence indicators defining transition points. Using real-world data from 490 population-based studies comprising 80 global regions and spanning over a century (1920–2023), we show spatiotemporal transitions across stages 1–3 and model transition towards stage 4. Understanding the evolution of IBD across epidemiologic stages allows healthcare systems to better prepare for the future worldwide burden of IBD.","manuscriptTitle":"The Global Evolution of Inflammatory Bowel Disease across Four Epidemiologic Stages","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-23 10:26:18","doi":"10.21203/rs.3.rs-3846147/v1","editorialEvents":[],"status":"published","journal":{"display":false,"email":"[email protected]","identity":"nature","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"nature","sideBox":"Learn more about [Nature](http://www.nature.com/nature/)","snPcode":"","submissionUrl":"","title":"Nature","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4654cdd4-4ead-491c-9175-c4f1af7c3f24","owner":[],"postedDate":"January 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":28048395,"name":"Health sciences/Diseases/Gastrointestinal diseases/Inflammatory bowel disease"},{"id":28048396,"name":"Health sciences/Medical research/Epidemiology"}],"tags":[],"updatedAt":"2025-03-26T15:13:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-23 10:26:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3846147","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3846147","identity":"rs-3846147","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}