Global burden of inflammatory bowel disease

The inflammatory bowel diseases ulcerative colitis and Crohn's disease are chronic, relapsing disorders of the gastrointestinal tract. Collectively, these conditions can result in debilitating physical and psychosocial symptoms for patients and affect society through loss of schooling, absenteeism, and health-care costs. More than 2 million Europeans and 1·5 million North Americans have inflammatory bowel disease (IBD), with the majority of health-care costs driven by medication. The cause of IBD is unknown, but it is considered to be the result of an inappropriate immune response against environmental factors, including luminal and microbial antigens, in genetically susceptible hosts.1de Souza HS Fiocchi C Immunopathogenesis of IBD: current state of the art.Nat Rev Gastroenterol Hepatol. 2016; 13: 13-27Crossref PubMed Scopus (820) Google Scholar Over the past decade, large-scale genome-wide association studies have identified more than 200 genetic loci associated with IBD, some of which are shared with other chronic autoimmune diseases. The majority of loci are shared across diverse ancestral groups, apart from major European risk variants such as NOD2 (the first identified mutation that mediates immune response to gut bacteria) and IL23R, which are not present in east Asians.2Jostins L Ripke S Weersma RK et al.Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.Nature. 2012; 491: 119-124Crossref PubMed Scopus (3227) Google Scholar However, this large investment in genetics has not yet resulted in direct benefit on patient outcomes, either through identification of risk-stratification tools for disease progression or for predicting response to therapy, resulting in renewed interest in understanding the effects of environmental exposures. Epidemiological studies of migrant populations have shown that the offspring of individuals immigrating from regions with low IBD prevalence in Asia to the developed world have similarly high incidence of IBD compared with children of non-immigrants, indicating that risk might be triggered by earlier life exposure to environmental antigens.3Benchimol EI Mack DR Guttmann A et al.Inflammatory bowel disease in immigrants to Canada and their children: a population-based cohort study.Am J Gastroenterol. 2015; 110: 553-563Crossref PubMed Scopus (149) Google Scholar The rising incidence observed in newly industrialised nations is associated with striking dietary changes, including increased exposure to processed food, refined sugars, dairy, and less plant-based fibres.4Windsor JW Kaplan GG Evolving epidemiology of IBD.Curr Gastroenterol Rep. 2019; 21: 40Crossref PubMed Scopus (116) Google Scholar In China, since the first reported case of IBD in 1956, more than 260 000 people are now living with IBD—a rise paralleled with westernisation of diet and culture.5Kaplan GG Ng SC Globalisation of inflammatory bowel disease: perspectives from the evolution of inflammatory bowel disease in the UK and China.Lancet Gastroenterol Hepatol. 2016; 1: 307-316Summary Full Text Full Text PDF PubMed Scopus (115) Google Scholar Other environmental exposures linked to an increased risk for development of IBD include smoking in Crohn's disease, childhood antibiotic exposure, non-steroidal drugs, stress, and the hygiene hypothesis;6Ananthakrishnan AN Epidemiology and risk factors for IBD.Nat Rev Gastroenterol Hepatol. 2015; 12: 205-217Crossref PubMed Scopus (882) Google Scholar protective factors include smoking in ulcerative colitis, appendectomy, and breastfeeding. In The Lancet Gastroenterology & Hepatology, the GBD 2017 Inflammatory Bowel Disease Collaborators report global prevalence, mortality, and overall burden of IBD from 195 countries and territories between 1990 and 2017, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017.7GBD 2017 Inflammatory Bowel Disease CollaboratorsThe global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2019; (published online Oct 21)https://doi.org/10.1016/S2468-1253(19)30333-4Google Scholar Similar to observations reported in a systematic review of cohort studies in The Lancet in 2018,8Ng SC Shi HY Hamidi N et al.Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.Lancet. 2018; 390: 2769-2778Summary Full Text Full Text PDF PubMed Scopus (2432) Google Scholar incidence has stabilised in the west, but prevalence increased because of improved survival. Conversely, the authors report rapidly rising incidence rates in newly industrialised countries in South America, eastern Europe, Asia, and Africa, which are likely yet to peak, but lower prevalence. Furthermore, the rise in earlier onset IBD means longer disease duration and potentially more complex disease into adulthood and old age, bringing associated challenges of managing IBD in an ageing population, with concurrent comorbidity and risk of treatment-related adverse events. Reassuringly, reductions in mortality were observed (eg, the age-standardised death rate decreased from 0·61 [95% uncertainty interval 0·55–0·69] per 100 000 population in 1990 to 0·51 [0·42–0·54] in 2017), with improved survival attributed by the authors to timelier introduction of biological agents, colon cancer surveillance, and better surgical techniques. Collectively, more than 6·8 million people are estimated to be living with IBD worldwide. This burden to patients and society will require investment into research to better understand the interplay of genes, the microbiome, and the environment, to address traditional paradigms of chronic disease prevention. Enhanced understanding of the very early stages of IBD from preclinical samples might eventually offer possibilities for disease prevention in high-risk individuals (eg, first-degree relatives) through manipulation of the microbiome or dietary therapies.9Torres J Burisch J Riddle M Dubinsky M Colombel JF Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities.Gut. 2016; 65: 1061-1069Crossref PubMed Scopus (51) Google Scholar The Crohn's and Colitis Canada Genetic, Environmental, Microbial (GEM) Project, which is prospectively enrolling first-degree relatives of Crohn's disease probands with biomarker collection and environmental history exposure, might provide novel insights into such preclinical disease pathways. Ultimately, the goal is to either interrupt these diseases preclinically in high-risk individuals—an approach that has recently shown promise in type 1 diabetes10Herold KC Bundy BN Long SA et al.An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes.N Engl J Med. 2019; 381: 603-613Crossref PubMed Scopus (330) Google Scholar—or to develop primary prevention strategies based on dietary interventions. The study by the GBD 2017 Inflammatory Bowel Disease Collaborators shows that data from large-scale population epidemiology studies are essential for providing insights into the cause of IBD that will ultimately result in a cure. VJ has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, and Celltrion; and speaker's fees from Takeda, Janssen, Shire, Ferring, AbbVie, and Pfizer. BGF has received consulting fees from Abbott/AbbVie, AdMIRx, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport, Aptevo Therapeutics, Asta Pharma, AstraZeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, Galen/Atlantica, GiCare Pharma, Gilead, Gossamer Pharma, GlaxoSmithKline, Inception IBD, Intact Therapeutics, JnJ/Janssen, Kyowa Kakko Kirin, Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestlé, Nextbiotix, Novonordisk, ParImmune, Parvus Therapeutics, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Qu Biologics, Rebiotix, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma, Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared, and Zyngenia; speaker's fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, UCB Pharma; grant/research support from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltech, Genentech/Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Janssen Research & Development, Pfizer, Receptos/Celgene International, Sanofi, Santarus, Takeda Development Center Americas, Tillotts Pharma, and UCB; is a member of the scientific advisory board for Abbott/AbbVie, Allergan, Amgen, AstraZeneca, Atlantic Pharma, Avaxia Biologics, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestlé, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma, and UCB Pharma; and is a member of the board of directors for Robarts Clinical Trials. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Full-Text PDF Open Access