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Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: a Systematic Review
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Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: a Systematic Review Q11
Paulo Gustavo Kotze,*,a Fox E. Underwood,‡ Aderson Omar Mourão Cintra Damião,§ Jose Geraldo P. Ferraz,k Rogerio Saad-Hossne,¶ Martin Toro,# Beatriz Iade,** Francisco Bosques-Padilla,‡‡ Fábio Vieira Teixeira,§§ Fabian Juliao-Banos,kk Daniela Simian,¶¶ Subrata Ghosh,## Remo Panaccione,k Siew C. Ng,*** and Gilaad G. Kaplan‡,a *IBD Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil; ‡Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; §Department of Gastroenterology, University of São Paulo (USP), São Paulo, Brazil; kDivision of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; ¶São Paulo State University (UNESP), Botucatu, Brazil; #Hospital Universitario de la Universidad Nacional de Cuyo, Mendoza, Argentina; **Hospital Maciel, Montevideo, Uruguay; ‡‡Autonomous University of Nuevo Leon, San Nicolas de los Garza, Mexico; §§Clinica Gastrosaúde, Marília, São Paulo, Brazil; kkHospital Pablo Tobon Uribe, Medellin, Colombia; ¶¶Clinica Las Condes, Santiago, Chile; ##Institute of Translational Medicine, NIHR Biomedical Research Centre, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom; and ***Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong, SAR, China BACKGROUND & AIMS:
The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean.
METHODS:
We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn’s disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis.
RESULTS:
The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991–1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990–2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012–2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001– 2003 and 6.2% in 2004–2014.
CONCLUSIONS:
In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status.
Keywords: Anti-TNF; Ethnicity; Race; Risk Factor; Incidence; Prevalence; Inflammatory Bowel Disease.
a
Authors share co-first authorship.
Abbreviations used in this paper: CD, Crohn’s disease; IBD, inflammatory bowel diseases; TNF, tumor necrosis factor; UC, ulcerative colitis.
© 2019 by the AGA Institute. Published by Elsevier, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/). 1542-3565 https://doi.org/10.1016/j.cgh.2019.06.030
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n the 21st century, the incidence of Crohn’s disease (CD) and ulcerative colitis (UC) stabilized in the Western world.1,2 The prevalence of the inflammatory bowel diseases (IBD) exceeded 0.3% of the population in North America, Europe, and Oceania.2 In contrast, the prevalence of IBD in Asia, Africa, and South America was a fraction of the Western world. However, as newly industrialized countries experienced Westernization, a wave of steadily rising incidence has followed.2–5 Population-based studies in Latin America and the Caribbean, regions including countries and territories in North America (ie, Mexico), Central America, and South America, have demonstrated rising incidence of IBD.6–11 However, data from the Southwest Hemisphere have been scarcer and less well-organized because of less developed healthcare infrastructure available to capture clinical outcomes in registries and administrative healthcare databases.2,6 We conducted a systematic literature review of all CD and UC studies in Latin America and the Caribbean that reported phenotypic characteristics, hospitalization, surgery, drug penetration, incidence, or prevalence of IBD patients of any age or sex.
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Methods Literature Search Cohort and cross-sectional studies from all Latin American and Caribbean countries and territories that reported incidence, prevalence, hospitalization, surgery, medication, or phenotypic characteristics of IBD patients were identified by searching MEDLINE and EMBASE to September 12, 2018. SciELO, an Open Access database focused predominantly on research in Latin America,12 was also searched to uncover articles that were not indexed in MEDLINE or EMBASE. Studies were limited to regional or national samples as well as population-based studies in the following regions: Latin America, Central America, the Caribbean, and South America. Appendix 1 provides a list of countries and territories that were searched in each database. The systematic review was performed in accordance with the quality of reporting guidelines according to MOOSE13 and PRISMA.14 The search was not limited by language. The search was performed by an author with postgraduate training in systematic review (F.E.U.).
Study Selection Search results were reviewed by 2 independent reviewers (P.G.K., F.E.U.), first as abstracts and then as fulltexts. Abstracts were excluded if they did not report on IBD populations in Latin America or the Caribbean. Review articles were set aside for hand searching of their reference lists for any studies not found in the database search. Additional articles were found from expert
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What You Need to Know Background We performed a systematic review to identify clinical and epidemiologic features of inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, in Latin America (including Mexico, Central America, and South America) and the Caribbean. Findings The incidence and prevalence of IBD are increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status. Implications for patient care Physicians in Latin America and the Caribbean should be aware that more patients will be presenting with IBD.
knowledge of the IBD literature in Latin America. Articles in Portuguese or Spanish were reviewed and translated by P.G.K. Disagreements were resolved through discussion with a third reviewer (G.G.K.). Abstracts were accepted if no follow-up, full-text study had yet been published.
Data Extraction Data were extracted independently by P.G.K. and F.E.U. Data extracted included first author, country or territory (including states within Brazil), local region, study period, age groups, incidence, prevalence, hospitalization (crude values), in addition to numbers and percentages of patients, medications prescribed, proportion of surgical treatment in the cohorts, and phenotypic characteristics (ie, Montreal classification). When multiple studies used the same data source, we extracted relevant data from the most recent study population. Disagreements were resolved through discussion with a third reviewer (G.G.K.). If necessary, authors were contacted to provide details of the data presented in their studies. Quality of the studies was assessed independently by using a modified version of the Cochrane Collaboration–endorsed Newcastle-Ottawa Quality Assessment Scale.15
Data Summarization Tables and figures were created to describe different aspects of IBD populations in Latin America and the Caribbean in our review as follows: incidence per 100,000 person-years, prevalence per 100,000 persons, ratio of patients diagnosed with UC versus CD at time of
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Latin IBD Characteristics
study entry, proportion of age at study entry point, proportion of the patients’ disease location and behavior at study entry, proportion prescribed IBD medications (ie, steroids, mesalamine, immunomodulators, anti–tumor necrosis factor (TNF) agents), and proportion of the IBD population with an intestinal resection. The UC:CD ratio represents the average of UC (combined with unclassified inflammatory bowel disease if reported separately) to CD ratios, per country or per Brazilian state, limited to one ratio per study (the longest period of data per study). The UC:CD ratio was illustrated as 6 map classes using Jenks Natural Breaks.16 The 6 selected classes were 0.48–0.68, 0.68–1.20, 1.20–1.94, 1.94–3.38, 3.38–4.87, and 4.87–5.84 (a value greater than 1 denotes an area where UC is more common than CD). The static maps were created by using QGIS 2.18 (Open Source Geospatial Foundation, Chicago, IL). An interactive Web-linked map was created to provide a narrative description of the key clinical and epidemiologic findings for each region. The interactive map (http://people.ucalgary.ca/wggkaplan/ibd-latinct. html) was created with ArcGIS Pro 2.3.0 and ArcGIS Online (Environmental Systems Research Institute, Redlands, CA).
Results Studies Selected We identified 1434 articles that fulfilled our selection criteria: 255 from MEDLINE, 722 from EMBASE, and 457
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from SciELO. Eighty-three articles were selected for fulltext review from MEDLINE and EMBASE, and 43 articles were selected from SciELO. After full-text review, 41 articles were selected from MEDLINE and EMBASE, 25 articles were selected from SciELO, and 4 articles were discovered outside of the database searches. In total, 61 articles were used for data extraction (Appendix 2). An article matrix (Appendix 3) denotes the IBD information provided in each study in the systematic review, with some studies providing information on more than 1 health measure: incidence (9), prevalence (8), UC:CD ratio (35), phenotype (46), medication (27), hospitalization (8), and surgery (38). Appendix 4 reports the quality assessment of the studies, Appendix 5 lists the MOOSE13 checklist, and Appendix 6 lists the PRISMA14 checklist.
Incidence The incidence of both CD and UC steadily increased during the last decades (Figure 1, Table 1). For example, the incidence of IBD in Brazil was reported as 0.08 per 100,000 person-years in 1988,17 yet the incidence of CD rose sharply from 0.68 in 1991–199511 to 3.50 in 2001–2005,11 reaching a peak incidence of CD of 5.48 in 2015,18 whereas from 1991–1995 to 2001–2005 UC incidence rose from 3.8611 to 5.3,19 with a peak of 8.00 in 2015.18 In Puerto Rico, incidence for CD and UC more than doubled from 1996 to 2000 (3.07 to 7.74).20 Argentina, Uruguay, Guadeloupe and Martinique, and Panama all reported incidence values between 0.39 and 4.39.7,21,22
Figure 1. Incidence. CD, Crohn’s disease; UC, ulcerative colitis.
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Table 1. Incidence per 100,000 Person-Years First author and publication year de la Cal 199921 Edwards 20088 Edwards 20088 Edwards 20088 Edwards 20088 Edwards 20088 Victoria 200911 Parente 201517 Victoria 200911 Parente 201517 Victoria 200911 Victoria 200911 Parente 201517 Parente 201517 Gasparini 201818 Gasparini 201818 Lima-Martins 201819 Gasparini 201818 Gasparini 201818 Edouard 20057 de la Cal 199921 Appleyard 200420 Appleyard 200420 Appleyard 200420 Appleyard 200420 Appleyard 200420 Buenavida 201122
Country
Study period
Argentina Barbados Barbados Barbados Barbados Barbados Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Guadeloupe and Martinique Panama Puerto Rico Puerto Rico Puerto Rico Puerto Rico Puerto Rico Uruguay
1987–1993 1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 1986–1990 1988 1991–1995 1998 1996–2000 2001–2005 2008 2012 2012 2013 2014 2014 2015 1997–1999 1987–1993 1996 1997 1998 1999 2000 2007–2008
IBD incidence
CD incidence
1.58 2.56 3.60 3.05 2.19 0.98 0.08 4.54 0.34 8.24 7.98 1.39 1.26 13.57 13.55 7.7 12.65 13.49 4.39
0.28 0.64 1.30 0.71 0.61 0.24 0.08 0.68 0.20 1.48 3.50 0.54 0.61 6.83 6.62 2.4 5.66 5.48 1.95
3.07 4.1 5.0 4.7 7.74 2.63
0.49 1.2 0.9 1.2 1.96 0.39
UC incidence 2.17 1.30 1.92 2.30 2.34 1.58 0.74 0.00 3.86 0.14 6.76 4.48 0.85 0.65 6.73 6.92 5.3 6.99 8.00 2.44 1.20 2.57 2.8 4.0 3.4 5.78 2.25
CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.
Prevalence
Phenotypes (Montreal Classification)
Prevalence of IBD steadily rose in Latin America and the Caribbean (Figure 2, Table 2). For example, the prevalence of CD in Brazil rose from 0.24 per 100,000 persons (1986–1990)11 to 24.1 (2014),19 whereas the prevalence of UC rose from 0.9911 to 14.119 in the same period (Table 2). Prevalence of IBD was also high in Argentina (97.2),23 Barbados (61),8 Colombia (57.62 in 201225), and Puerto Rico (38.22 in 2005).26
Ulcerative Colitis:Crohn’s Disease Ratio The ratio of UC to CD patients at study entry was greater than 1 in all regions with the exception of 3 Brazilian states (Figure 3). Within Brazil, which had an overall country UC:CD ratio of 1.081 and a range of 0.481–1.936, the Brazilian states of Alagoas, Rio de Janeiro, and Mato Grosso do Sul had UC:CD ratios of 0.481, 0.679, and 0.596, respectively. France’s regions, Guadeloupe and Martinique, had a UC:CD ratio of 1.200. UC was more common than CD in Argentina (4.308), Cuba (4.867), Chile (2.914), Colombia (5.837), Mexico (4.798), Peru (3.375), Uruguay (4.160), and Venezuela (4.668) (Figure 3). The UC:CD ratios of the remaining countries were 2.429, 2.574, and 2.572 for Trinidad and Tobago, Barbados, and the U.S. territory Puerto Rico, respectively.
Phenotypic characteristics of CD and UC varied across Latin America and the Caribbean (Appendix 7). The most common phenotypic characteristics for CD were age of diagnosis between 17 and 40 years (Montreal classification A2), ileocolonic disease extent (L3), and inflammatory disease behavior (B1). Perianal CD varied from 12% in a Brazilian study27 up to 53% in a study from Peru.28 Disease extent of UC varied; distal proctitis (Montreal classification E1) spanned from 0% in a Brazilian study29 to 55.35% in a study from Puerto Rico,30 left-sided colitis (Montreal classification E2) varied from 11.1%31 to 62.9%32 in different studies from Peru, and extensive colitis (Montreal classification E3) was 12% in a Brazilian study33 and up to 77% in Argentina34 (Appendix 7).
Medications The mesalamine compounds were commonly used for CD, varying from 21.2% in Brazil35 to 100% in Cuba.36 High percentages of mesalamine use were noted in UC patients, from 56.36%19 to 100%.37 Use of mesalamine for CD patients in Brazil had fallen from 81.6% in 1970–199838 to 31.46% in 2013–2014,19 whereas use for UC patients fell from 93.2% in 1980–199910 to 56.36% in 2013–201419 (Appendix 8). Steroids were still widely used in the region, with percentages varying in CD and UC
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Figure 2. Prevalence. CD, Crohn’s disease; UC, ulcerative colitis.
from 13.3%39 to 87.5%.40 Immunomodulator use for CD patients in Brazil rose from 8.3% in 1970–199838 to 71.7% in 2013–2014,19 whereas use for UC patients rose from 5.4% in 1980–199910 to 19.4% in 2013–201419 (Appendix 8). Since approval of anti-TNF use in 2000, the proportion of patients with CD prescribed infliximab or adalimumab has risen steadily (Figure 4A, Appendix 8). For example, in Brazil, 29.6% of CD patients received anti-TNF from 2005 to 2012,41 rising to 43.4% in 2013–201419 (Figure 4A, Appendix 8). In contrast, the proportion of UC patients prescribed anti-TNF after 2006 remained consistently low. For example, only 4.5% of UC patients were prescribed anti-TNF in Brazil in 2013–201419 and 7% and 1.4% in Uruguay in 2016–201742 (Figure 4B, Appendix 8).
Hospitalization and Surgery Hospitalizations were highest in Colombia40 (CD, 75.0%; UC, 42.9%) and Peru43 (CD, 75.0%; UC, 51.8%) and lowest in Brazil, where CD hospitalization had fallen from 83.3% in 1980–199910 to 29.2% in 2006,44 and UC hospitalization had fallen from 63.0% in 1980–199910 to 43.8% in 2011–201245 (Appendix 9). Surgery for CD and UC steadily declined over time in several regions of Latin America: in Brazil from 1980–199910 (CD, 57.8%; UC, 21.9%) to 2016–201746 (CD, 31.7%; UC, 5.8%) and in Peru from 70.5% (CD) in 1990–201028 to 50.0% (CD) in 2004–201443 (Figure 4, Appendix 10). In contrast, the proportion of colectomy for UC remained stable in many regions: in Peru from 6.9% in 2001–200332 to 6.2% in 2004–201443 and in
Table 2. Prevalence per 100,000 Persons First author and publication year Sobrero 200923 Edwards 20088 Victoria 200911 Victoria 200911 Victoria 200911 Victoria 200911 Parente 201517 Lima-Martins 201819 Yepes-Barreto 201024 Juliao 201825 Vendrell 201326 Vendrell 201326 Vendrell 201326 Vendrell 201326
Country
Study period
IBD prevalence
CD prevalence
UC prevalence
Argentina Barbados Brazil Brazil Brazil Brazil Brazil Brazil Colombia Colombia Puerto Rico Puerto Rico Puerto Rico Puerto Rico
2007 2004 1988 1993 1998 2003 2012 2014 2006 2012 2002 2003 2004 2005
97.2 61.0 1.23 5.67 13.52 20.46 12.8 38.2 29 57.62 33.23 32.42 37.26 38.22
15.0 16.7 0.24 0.90 2.32 5.65
82.2 44.3 0.99 4.77 11.2 14.81
24.1 7 5.85 11.43 11.96 12.93 14.9
14.1 22 51.77 21.72 20.46 24.33 23.32
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Figure 3. UC:CD ratio. CD, Crohn’s disease; UC, ulcerative colitis.
Uruguay from 1951–200347 (UC, 8.3%) to 1985–201542 (UC, 10.5%) (Figure 4, Appendix 10).
Discussion Our systematic review identified significant gaps in high quality population-based studies of IBD in Latin America and the Caribbean. Nonetheless, the available data indicate notable heterogeneity between the countries that may be driven by factors such as historical colonization, culture, socioeconomic status, genetic background, lifestyle, and diet. Future studies should focus on developing large population-based registries that describe the epidemiology, natural history, and outcomes of IBD. Despite important variation in the incidence of both UC and CD in Latin America and the Caribbean, our review suggests that incidence has steadily increased during the past decades. In a descriptive review of the incidence and prevalence of IBD in Latin America, Farrukh and Mayberry9 speculated that epidemiologic patterns have mirrored the evolution of IBD in Spain during the 20th century. Historically, UC was diagnosed more commonly than CD in the Western world. During the 20th century, numerous studies confirmed a transition in the UC:CD ratio such that CD approximated the diagnosis of UC and in many Western countries became more common. Similar to the Western world, regions within Latin America that are associated with higher economic development, industrialization, and Westernization of environmental exposures (eg, diet) reported higher proportions of CD. Improved healthcare access and delivery may also influence the diagnosis of CD.
After decades of rising incidence, the prevalence of IBD has been expanding. Consequently, the prevalence of IBD in Latin America is equivalent to many countries in Asia and is approximating countries in Southern and Eastern Europe. As more individuals live with IBD, caring for these patients will exact a tremendous stress on the healthcare systems within Latin America and the Caribbean. Expansion of national registries of IBD is necessary for surveillance of the burden of IBD across these countries. Important variation in the prescription of medications was observed throughout the continent. The use of corticosteroids was high for both diseases. Moreover, the use of mesalamine compounds for CD is common, probably because of difficult access to biologics in some areas. The proportion of patients treated with anti-TNF therapy was also variable between the countries. Some studies demonstrated approximately 40% of biologic penetration for CD in more developed areas. Case series from other countries did not have such a high penetration, possibly because of difficulties in patient care, access to these agents, and the lack of specific local IBD study groups or associations that could increase the level of patient care. With the rising prevalence of IBD, countries in Latin America and the Caribbean can expect higher rates of hospitalization and surgeries and, in turn, greater utilization of expensive biologics to treat flares and prevent complications of IBD. Our review demonstrated an increase in the use of anti-TNF therapy in the management of CD, mostly after the approval of infliximab around the year 2000. In juxtaposition, surgery for CD decreased in the same period. Increased use of anti-TNF therapy for
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Figure 4. Proportion of patients with Crohn’s disease (A) and ulcerative colitis (B) prescribed anti-TNF therapy and undergoing an intestinal resection. CD, Crohn’s disease; TNF, tumor necrosis factor; UC, ulcerative colitis.
CD was likely related to greater disease awareness, better diagnostic techniques, and management strategies. In contrast, surgery rates for UC in the 21st century were relatively stable throughout Latin America. Similarly, the use of anti-TNF therapy for UC did not increase significantly in Latin American and Caribbean countries after 2006 when the ACT randomized controlled studies demonstrated the efficacy of infliximab in UC.48 These findings may be explained by difficulties in accessing anti-TNF therapies for UC, mostly on the basis of limited reimbursement from both public and private payors in many countries. As access to biologics expands and
increased awareness of therapeutic strategies for managing IBD (eg, less reliance on mesalamine for treatment of CD) rises, we can anticipate that rates of hospitalization and surgery will continue to fluctuate in this region of the globe. The major strength of our review was the inclusion of a local database (SciELO) in addition to MEDLINE and EMBASE. By including articles written in local languages, more data could be captured, and we believe this could be used as an example in methodology for future reviews in different parts of the world. This systematic review has some limitations that may influence the
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interpretation of our results. The information collected varied between studies, and data were based predominantly on cross-sectional studies. Most of the data were derived from tertiary centers from larger cities. Variables such as frequency of medication use, hospitalization, and surgery are described in crude values, with no defined follow-up. As the healthcare infrastructure in Latin American and Caribbean regions advances to include greater use of electronic administrative databases, a more complete picture of the health services and outcomes of IBD will become available. Furthermore, temporal trend analyses on incidence and prevalence of IBD were derived from a few population-based studies with sufficient longitudinal data, and thus extrapolation of the rising incidence and prevalence of IBD throughout Latin America and the Caribbean is an assumption that needs to be confirmed in future population-based studies. Finally, the quality assessment demonstrated that the majority of included studies were of low quality. For example, only 16 of the 61 studies were populationbased. Outcomes such as medication usage and surgery need to be interpreted cautiously and in the context of the limitation of including lower quality studies. Moreover, the paucity of high quality studies highlights an important gap in the literature and serves as a clarion call to invest in the infrastructure, resources, and personnel necessary to conduct non-biased observational research in Latin America and the Caribbean. In summary, this systematic review on the clinical and epidemiologic characteristics of IBD in Latin America and the Caribbean demonstrated that the incidence and prevalence of IBD may be increasing and that the UC:CD ratios are evolving throughout the continent. The phenotypes of IBD observed varied slightly between the countries but are consistent to what is seen in other parts of the world. The increase in the use of anti-TNF agents for CD may be correlated to a decrease in surgery; the same pattern was not observed in UC. This comprehensive systematic review outlines the important burden of IBD in Latin America and the Caribbean and emphasizes the need for better registries and populationbased studies in this region of the world.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at https://doi.org/10.1016/j.cgh.2019.06.030.
2. Ng SC, Shi HY, Hamidi N, et al. The worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017; 390:2769–2778.
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871 872 873 Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat 874 Rev Gastroenterol Hepatol 2015;12:720–727. 875 Kaplan GG, Ng SC. Globalisation of inflammatory bowel disease: 876 perspectives from the evolution of inflammatory bowel disease in 877 the UK and China. Lancet Gastroenterol Hepatol 2016;1:307–316. 878 Calderon M, Minckas N, Nunez S, et al. Inflammatory bowel 879 disease in Latin America: a systematic review. Value Health Reg 880 Issues 2018;17:126–134. 881 Edouard A, Paillaud M, Merle S, et al. Incidence of inflammatory 882 bowel disease in the French West Indies (1997-1999). Gastro883 enterol Clin Biol 2005;29:779–783. 884 Edwards CN, Griffith SG, Hennis AJ, et al. Inflammatory bowel 885 disease: incidence, prevalence, and disease characteristics in Barbados, West Indies. Inflamm Bowel Dis 2008;14:1419–1424. 886 Farrukh A, Mayberry JF. Inflammatory bowel disease in Hispanic 887 communities: a concerted South American approach could 888 identify the aetiology of Crohn’s disease and ulcerative colitis. 889 Arq Gastroenterol 2014;51:271–275. 890 Souza MH, Troncon LE, Rodrigues CM, et al. [Trends in the 891 occurrence (1980-1999) and clinical features of Crohn’s disease 892 and ulcerative colitis in a university hospital in southeastern 893 Brazil]. Arq Gastroenterol 2002;39:98–105. 894 Victoria CR, Sassak LY, Nunes HR. Incidence and prevalence 895 rates of inflammatory bowel diseases, in midwestern of Sao 896 Paulo State, Brazil. Arq Gastroenterol 2009;46:20–25. 897 Scientific Electronic Library Online. 2018. Available at: http://www. 898 scielo.org/php/index.php?lang¼en/. Accessed September 12, 899 2018. 900 Stroup DF, Berlin JA, Morton SC. Meta-analysis of observational 901 studies in epidemiology: a proposal for reporting. JAMA 2000; 283:2008–2012. 902 Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement 903 for reporting systematic reviews and meta-analyses of studies 904 that evaluate health care interventions: explanation and elabo905 ration. PLoS Medicine 2009;6:1–28. 906 Wells GA, Shea B, O’Connel, et al. The Newcastle-Ottawa Scale 907 (NOS) for assessing the quality of nonrandomised studies in 908 meta-analyses. 2014. Available at: http://ohri.ca/programs/ 909 Q7 clinical_epidemiology/oxford.asp. Accessed. 910 Jenks GF. The data model concept in statistical mapping. Int 911 Yearb Carto 1967;7:186–190. 912 Parente JM, Coy CS, Campelo V, et al. Inflammatory bowel 913 disease in an underdeveloped region of Northeastern Brazil. 914 World J Gastroenterol 2015;21:1197–1206. 915 Gasparini RG, Sassaki LY, Saad-Hossne R. Inflammatory bowel 916 disease epidemiology in São Paulo State, Brazil. Clin Exp Q8 917 Gastroenterol (in press). 918 Lima-Martins A, Volpato RA, Zago-Gomes MdP. The prevalence 919 and phenotype in Brazilian patients with inflammatory bowel disease. BMC Gastroenterology 2018;18:87. 920 921 Appleyard CB, Hernandez G, Rios-Bedoya CF. Basic epidemiology of inflammatory bowel disease in Puerto Rico. Inflamm 922 Bowel Dis 2004;10:106–111. 923 de la Cal JAL, Canton C, Hermida C, et al. Estimated incidence 924 of inflammatory bowel disease in Argentina and Panama (1987925 1993). Rev Esp Enferm Dig 1999;91:277–286. 926 Buenavida G, Casañas A, Vasquez C, et al. Incidence of in927 flammatory bowel disease in five geographical areas of Uruguay 928
3. Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology 2017; 152:313–321. 4. 5.
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in the biennial 2007-2008. Acta Gastroenterologica Latinoamericana 2011;41:281–287. 23. Sobrero MJ, Varela E, Gonzalez ML, et al. Prevalence of inflammatory bowel disease in a university hospital health maintenance organization. Gastroenterology 2009;1:A361–A362. 24. Yepes-Barreto IdJ, Carmona R, Díaz F, et al. Prevalencia y características demográficas de la enfermedad inflamatoria intestinal en Cartagena, Colombia. Revi Colomb Gastroenterol 2010;25:107–111. 25. Juliao F, Calixto O. Prevalence of crohn’s disease and ulcerative colitis in colombia: analysis of the integral information system of social protection (sispro). Am J Gastroenterol 2018;113(Suppl 1):S9. 26. Vendrell R, Venegas HL, Perez CM, et al. Differences in prevalence of inflammatory bowel disease in Puerto Rico between commercial and government-sponsored managed health care insured individuals. Boletin de la Asociacion Medica de Puerto Rico 2013;105:15–19. 27. Souza MMd, Belasco AGS, Aguilar-Nascimento JEd. Perfil epidemiológico dos pacientes portadores de doença inflamatória intestinal do estado de Mato Grosso. Rev Brasi Coloproctol 2008;28:324–328. 28. Bendano T, Frisancho O. [Clinical and evolutive profile of Crohn’s disease in Hospital Rebagliati (Lima-Peru)]. Rev Gastroenterol Peru 2010;30:17–24. 29. Barros PACd, Silva AMRd, Lins-Neto MÁdF. The epidemiological profile of inflammatory bowel disease patients on biologic therapy at a public hospital in Alagoas. J Coloproctol (Rio J) 2014;34:131–135. 30. Moreno JM, Rubio CE, Torres EA. [Inflammatory disease of the gastrointestinal tract at the University Hospital, Medical Center, Puerto Rico. 1980-87]. Bol Asoc Med P R 1989; 81:214–218. 31. Illescas L, Garcia L, Faggioni F, et al. [Ulcerative colitis: a 52 years retrospective study]. Rev Gastroenterol Peru 1999;19:116–123. 32. Calderon AV, Velarde OF, Yoshidaira MY, et al. [Clinical and epidemiological profile of ulcerative colitis in a hospital in Lima]. Rev Gastroenterol Peru 2004;24:135–142. 33. Delmondes LM, Nunes MO, Azevedo AR, et al. Clinical and sociodemographic aspects of inflammatory bowel disease patients. Gastroenterology 2015;8:207–215. 34. Ruiz JA, Orsi M, Aliboni V, et al. Pediatric inflammatory bowel disease in a Latin-American population from Buenos Aires: multicenter study. Gastroenterology 2009;1:A356. 35. Kleinubing-Júnior H, Pinho MdSL, Ferreira LC, et al. Perfil dos pacientes ambulatoriais com doenças inflamatórias intestinais. ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) 2011;24:200–203. 36. García OMH, Gomes SA, Jiménez OMV, et al. Caracterización de pacientes con enfermedad de Crohn atendidos en el Instituto de Gastroenterología de Cuba. Rev Cubana Investig Bioméd 2014;33:253–267. 37. de la Cruz-Guillen AA, Cortes-Espinosa T, Sanchez-Chavez X, et al. Clinical behavior of chronic nonspecific ulcerative colitis in patients of CMN 20 de Noviembre, ISSSTE, and comparison with American bibliography. Medicina Interna de Mexico 2011; 27:224–230. 38. Gaburri PD, Chebli JM, de Castro LE, et al. [Epidemiology, clinical features and clinical course of Crohn’s disease: a study of 60 cases]. Arq Gastroenterol 1998;35:240–246. 39. Lima CA, Lyra AC, Mendes CMC, et al. Bone mineral density and inflammatory bowel disease severity. Braz J Med Biol Res 2017;50.
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40. Juliao-Baños F, Ruiz-Vélez MH, Flórez-Arango JF, et al. Fenotipo e historia natural de la enfermedad inflamatoria intestinal en un centro de referencia en Medellín-Colombia. Revi Colomb Gastroenterol 2010;25:240–251. 41. de Barros KSC, Flores C, Harlacher L, et al. Evolution of clinical behavior in Crohn’s disease: factors associated with complicated disease and surgery. Dig Dis Sci 2017;62:2481–2488. 42. Luciano MJ, Noria A, Iade B. Demographic, clinical, and therapeutic characteristics of a cohort of 238 patients with ulcerative colitis from two medical centres from Uruguay. J Crohns Colitis 2018;12(Suppl 1):S458–S459. 43. Paredes-Méndez J, Moreno GO, Rivas-Plata ALM, et al. [Epidemiological and clinical characteristics of inflammatory bowel disease in a tertiary referral hospital in Lima-Peru]. Rev Gastroenterol Peru 2016;36:209–218. 44. Santana GO, Lyra LG, Santana TC, et al. Crohn’s disease in one mixed-race population in Brazil. World J Gastroenterol 2007; 13:4489–4492. 45. da Silva BC, Lyra AC, Mendes CM, et al. The demographic and clinical characteristics of ulcerative colitis in a northeast Brazilian population. Biomed Res Int 2015;2015:359130. 46. Vivan TK, Santos BM, Santos CHMd. Quality of life of patients with inflammatory bowel disease. J Coloproctol (Rio J) 2017;37:279–284. 47. Iade B, Bianchi C, Espíndola F. Características clínicas de presentación y seguimiento de una cohorte de 121 pacientes con colitis ulcerosa crónica en Uruguay. Rev Méd Urug 2005; 21:298–302. 48. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462–2476. Reprint requests Address requests for reprints to: Paulo G. Kotze, MD, MsC, PhD, Colorectal Surgery Unit, IBD Outpatients Clinic, Cajuru University Hospital, Catholic University of Paraná (PUCPR), Rua Bruno Filgueira, 369 cj.1205, Curitiba, PR, Brazil CEP 80440-220. e-mail: [email protected]; fax: þ55-41-3022-5500 and Gilaad Kaplan, MD, MPH, FRCPC, 3D03-18, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6 Canada. e-mail: [email protected]; fax: (403) 270-7307.
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Acknowledgments G.G.K. is a CIHR Embedded Clinician Research Chair.
Q2
Conflicts of interest These authors disclose the following: Paulo Kotze has received consulting and speaker fees from AbbVie, Janssen, Pfizer, Takeda, and UCB. Aderson Damião has received consulting and speaker fees from AbbVie, Janssen, Pfizer, and Takeda. Rogerio Saad-Hossne has received consulting and speaker fees from AbbVie, Janssen, Pfizer, and Takeda. Martin Toro has received consulting and speaking fees from AbbVie, Janssen, and Takeda. Beatriz Iade has received consulting and speaking fees from AbbVie and Takeda. Fabio Vieira Teixeira has received consulting and speaking fees from AbbVie, Janssen, Ferring, and Takeda. Subrata Ghosh has received consulting fees from AbbVie, Janssen, Bristol-Myers Squibb, Pfizer, Celgene, and Boehringer-Ingelheim; served as a Scientific Advisory Board member for AbbVie, Janssen, and Takeda; and received research grants from AbbVie. Remo Panaccione has received consulting and speaker fees from AbbVie, Allergan, Celgene, Eli Lily, Ferring, Gilead, Janssen, Shire, and Takeda; served as a Scientific Advisory Board member for AbbVie, Allergan, Celgene, Eli Lily, Janssen, and Takeda; and received research grants from AbbVie, Janssen, and Takeda. Siew Ng has received consulting and speaker fees from AbbVie, Ferring, Janssen, Menarini, and Takeda; served as a Scientific Advisory Board member for AbbVie, Ferring, and Takeda; and received research grants from AbbVie, Ferring, and Janssen. Gilaad Kaplan has served as a speaker for Janssen, AbbVie, Takeda, and Pfizer; has received research support from Janssen, AbbVie, GlaxoSmith Kline, and Shire; and shares a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC, UTI Limited Partnership, assignee, Patent 62/555,397, 7 Sept 2017. The remaining authors disclose no conflicts.
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Q4 Funding Supported by Canadian Institutes of Health Research operating grant, funding Q10 reference number 162393.
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Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: a Systematic Review Q11
Paulo Gustavo Kotze,*,a Fox E. Underwood,‡ Aderson Omar Mourão Cintra Damião,§ Jose Geraldo P. Ferraz,k Rogerio Saad-Hossne,¶ Martin Toro,# Beatriz Iade,** Francisco Bosques-Padilla,‡‡ Fábio Vieira Teixeira,§§ Fabian Juliao-Banos,kk Daniela Simian,¶¶ Subrata Ghosh,## Remo Panaccione,k Siew C. Ng,*** and Gilaad G. Kaplan‡,a *IBD Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil; ‡Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; §Department of Gastroenterology, University of São Paulo (USP), São Paulo, Brazil; kDivision of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; ¶São Paulo State University (UNESP), Botucatu, Brazil; #Hospital Universitario de la Universidad Nacional de Cuyo, Mendoza, Argentina; **Hospital Maciel, Montevideo, Uruguay; ‡‡Autonomous University of Nuevo Leon, San Nicolas de los Garza, Mexico; §§Clinica Gastrosaúde, Marília, São Paulo, Brazil; kkHospital Pablo Tobon Uribe, Medellin, Colombia; ¶¶Clinica Las Condes, Santiago, Chile; ##Institute of Translational Medicine, NIHR Biomedical Research Centre, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom; and ***Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong, SAR, China BACKGROUND & AIMS:
The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean.
METHODS:
We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn’s disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis.
RESULTS:
The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991–1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990–2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012–2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001– 2003 and 6.2% in 2004–2014.
CONCLUSIONS:
In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status.
Keywords: Anti-TNF; Ethnicity; Race; Risk Factor; Incidence; Prevalence; Inflammatory Bowel Disease.
a
Authors share co-first authorship.
Abbreviations used in this paper: CD, Crohn’s disease; IBD, inflammatory bowel diseases; TNF, tumor necrosis factor; UC, ulcerative colitis.
© 2019 by the AGA Institute. Published by Elsevier, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/). 1542-3565 https://doi.org/10.1016/j.cgh.2019.06.030
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n the 21st century, the incidence of Crohn’s disease (CD) and ulcerative colitis (UC) stabilized in the Western world.1,2 The prevalence of the inflammatory bowel diseases (IBD) exceeded 0.3% of the population in North America, Europe, and Oceania.2 In contrast, the prevalence of IBD in Asia, Africa, and South America was a fraction of the Western world. However, as newly industrialized countries experienced Westernization, a wave of steadily rising incidence has followed.2–5 Population-based studies in Latin America and the Caribbean, regions including countries and territories in North America (ie, Mexico), Central America, and South America, have demonstrated rising incidence of IBD.6–11 However, data from the Southwest Hemisphere have been scarcer and less well-organized because of less developed healthcare infrastructure available to capture clinical outcomes in registries and administrative healthcare databases.2,6 We conducted a systematic literature review of all CD and UC studies in Latin America and the Caribbean that reported phenotypic characteristics, hospitalization, surgery, drug penetration, incidence, or prevalence of IBD patients of any age or sex.
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Methods Literature Search Cohort and cross-sectional studies from all Latin American and Caribbean countries and territories that reported incidence, prevalence, hospitalization, surgery, medication, or phenotypic characteristics of IBD patients were identified by searching MEDLINE and EMBASE to September 12, 2018. SciELO, an Open Access database focused predominantly on research in Latin America,12 was also searched to uncover articles that were not indexed in MEDLINE or EMBASE. Studies were limited to regional or national samples as well as population-based studies in the following regions: Latin America, Central America, the Caribbean, and South America. Appendix 1 provides a list of countries and territories that were searched in each database. The systematic review was performed in accordance with the quality of reporting guidelines according to MOOSE13 and PRISMA.14 The search was not limited by language. The search was performed by an author with postgraduate training in systematic review (F.E.U.).
Study Selection Search results were reviewed by 2 independent reviewers (P.G.K., F.E.U.), first as abstracts and then as fulltexts. Abstracts were excluded if they did not report on IBD populations in Latin America or the Caribbean. Review articles were set aside for hand searching of their reference lists for any studies not found in the database search. Additional articles were found from expert
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What You Need to Know Background We performed a systematic review to identify clinical and epidemiologic features of inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, in Latin America (including Mexico, Central America, and South America) and the Caribbean. Findings The incidence and prevalence of IBD are increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status. Implications for patient care Physicians in Latin America and the Caribbean should be aware that more patients will be presenting with IBD.
knowledge of the IBD literature in Latin America. Articles in Portuguese or Spanish were reviewed and translated by P.G.K. Disagreements were resolved through discussion with a third reviewer (G.G.K.). Abstracts were accepted if no follow-up, full-text study had yet been published.
Data Extraction Data were extracted independently by P.G.K. and F.E.U. Data extracted included first author, country or territory (including states within Brazil), local region, study period, age groups, incidence, prevalence, hospitalization (crude values), in addition to numbers and percentages of patients, medications prescribed, proportion of surgical treatment in the cohorts, and phenotypic characteristics (ie, Montreal classification). When multiple studies used the same data source, we extracted relevant data from the most recent study population. Disagreements were resolved through discussion with a third reviewer (G.G.K.). If necessary, authors were contacted to provide details of the data presented in their studies. Quality of the studies was assessed independently by using a modified version of the Cochrane Collaboration–endorsed Newcastle-Ottawa Quality Assessment Scale.15
Data Summarization Tables and figures were created to describe different aspects of IBD populations in Latin America and the Caribbean in our review as follows: incidence per 100,000 person-years, prevalence per 100,000 persons, ratio of patients diagnosed with UC versus CD at time of
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study entry, proportion of age at study entry point, proportion of the patients’ disease location and behavior at study entry, proportion prescribed IBD medications (ie, steroids, mesalamine, immunomodulators, anti–tumor necrosis factor (TNF) agents), and proportion of the IBD population with an intestinal resection. The UC:CD ratio represents the average of UC (combined with unclassified inflammatory bowel disease if reported separately) to CD ratios, per country or per Brazilian state, limited to one ratio per study (the longest period of data per study). The UC:CD ratio was illustrated as 6 map classes using Jenks Natural Breaks.16 The 6 selected classes were 0.48–0.68, 0.68–1.20, 1.20–1.94, 1.94–3.38, 3.38–4.87, and 4.87–5.84 (a value greater than 1 denotes an area where UC is more common than CD). The static maps were created by using QGIS 2.18 (Open Source Geospatial Foundation, Chicago, IL). An interactive Web-linked map was created to provide a narrative description of the key clinical and epidemiologic findings for each region. The interactive map (http://people.ucalgary.ca/wggkaplan/ibd-latinct. html) was created with ArcGIS Pro 2.3.0 and ArcGIS Online (Environmental Systems Research Institute, Redlands, CA).
Results Studies Selected We identified 1434 articles that fulfilled our selection criteria: 255 from MEDLINE, 722 from EMBASE, and 457
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from SciELO. Eighty-three articles were selected for fulltext review from MEDLINE and EMBASE, and 43 articles were selected from SciELO. After full-text review, 41 articles were selected from MEDLINE and EMBASE, 25 articles were selected from SciELO, and 4 articles were discovered outside of the database searches. In total, 61 articles were used for data extraction (Appendix 2). An article matrix (Appendix 3) denotes the IBD information provided in each study in the systematic review, with some studies providing information on more than 1 health measure: incidence (9), prevalence (8), UC:CD ratio (35), phenotype (46), medication (27), hospitalization (8), and surgery (38). Appendix 4 reports the quality assessment of the studies, Appendix 5 lists the MOOSE13 checklist, and Appendix 6 lists the PRISMA14 checklist.
Incidence The incidence of both CD and UC steadily increased during the last decades (Figure 1, Table 1). For example, the incidence of IBD in Brazil was reported as 0.08 per 100,000 person-years in 1988,17 yet the incidence of CD rose sharply from 0.68 in 1991–199511 to 3.50 in 2001–2005,11 reaching a peak incidence of CD of 5.48 in 2015,18 whereas from 1991–1995 to 2001–2005 UC incidence rose from 3.8611 to 5.3,19 with a peak of 8.00 in 2015.18 In Puerto Rico, incidence for CD and UC more than doubled from 1996 to 2000 (3.07 to 7.74).20 Argentina, Uruguay, Guadeloupe and Martinique, and Panama all reported incidence values between 0.39 and 4.39.7,21,22
Figure 1. Incidence. CD, Crohn’s disease; UC, ulcerative colitis.
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Table 1. Incidence per 100,000 Person-Years First author and publication year de la Cal 199921 Edwards 20088 Edwards 20088 Edwards 20088 Edwards 20088 Edwards 20088 Victoria 200911 Parente 201517 Victoria 200911 Parente 201517 Victoria 200911 Victoria 200911 Parente 201517 Parente 201517 Gasparini 201818 Gasparini 201818 Lima-Martins 201819 Gasparini 201818 Gasparini 201818 Edouard 20057 de la Cal 199921 Appleyard 200420 Appleyard 200420 Appleyard 200420 Appleyard 200420 Appleyard 200420 Buenavida 201122
Country
Study period
Argentina Barbados Barbados Barbados Barbados Barbados Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Brazil Guadeloupe and Martinique Panama Puerto Rico Puerto Rico Puerto Rico Puerto Rico Puerto Rico Uruguay
1987–1993 1980–1984 1985–1989 1990–1994 1995–1999 2000–2004 1986–1990 1988 1991–1995 1998 1996–2000 2001–2005 2008 2012 2012 2013 2014 2014 2015 1997–1999 1987–1993 1996 1997 1998 1999 2000 2007–2008
IBD incidence
CD incidence
1.58 2.56 3.60 3.05 2.19 0.98 0.08 4.54 0.34 8.24 7.98 1.39 1.26 13.57 13.55 7.7 12.65 13.49 4.39
0.28 0.64 1.30 0.71 0.61 0.24 0.08 0.68 0.20 1.48 3.50 0.54 0.61 6.83 6.62 2.4 5.66 5.48 1.95
3.07 4.1 5.0 4.7 7.74 2.63
0.49 1.2 0.9 1.2 1.96 0.39
UC incidence 2.17 1.30 1.92 2.30 2.34 1.58 0.74 0.00 3.86 0.14 6.76 4.48 0.85 0.65 6.73 6.92 5.3 6.99 8.00 2.44 1.20 2.57 2.8 4.0 3.4 5.78 2.25
CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.
Prevalence
Phenotypes (Montreal Classification)
Prevalence of IBD steadily rose in Latin America and the Caribbean (Figure 2, Table 2). For example, the prevalence of CD in Brazil rose from 0.24 per 100,000 persons (1986–1990)11 to 24.1 (2014),19 whereas the prevalence of UC rose from 0.9911 to 14.119 in the same period (Table 2). Prevalence of IBD was also high in Argentina (97.2),23 Barbados (61),8 Colombia (57.62 in 201225), and Puerto Rico (38.22 in 2005).26
Ulcerative Colitis:Crohn’s Disease Ratio The ratio of UC to CD patients at study entry was greater than 1 in all regions with the exception of 3 Brazilian states (Figure 3). Within Brazil, which had an overall country UC:CD ratio of 1.081 and a range of 0.481–1.936, the Brazilian states of Alagoas, Rio de Janeiro, and Mato Grosso do Sul had UC:CD ratios of 0.481, 0.679, and 0.596, respectively. France’s regions, Guadeloupe and Martinique, had a UC:CD ratio of 1.200. UC was more common than CD in Argentina (4.308), Cuba (4.867), Chile (2.914), Colombia (5.837), Mexico (4.798), Peru (3.375), Uruguay (4.160), and Venezuela (4.668) (Figure 3). The UC:CD ratios of the remaining countries were 2.429, 2.574, and 2.572 for Trinidad and Tobago, Barbados, and the U.S. territory Puerto Rico, respectively.
Phenotypic characteristics of CD and UC varied across Latin America and the Caribbean (Appendix 7). The most common phenotypic characteristics for CD were age of diagnosis between 17 and 40 years (Montreal classification A2), ileocolonic disease extent (L3), and inflammatory disease behavior (B1). Perianal CD varied from 12% in a Brazilian study27 up to 53% in a study from Peru.28 Disease extent of UC varied; distal proctitis (Montreal classification E1) spanned from 0% in a Brazilian study29 to 55.35% in a study from Puerto Rico,30 left-sided colitis (Montreal classification E2) varied from 11.1%31 to 62.9%32 in different studies from Peru, and extensive colitis (Montreal classification E3) was 12% in a Brazilian study33 and up to 77% in Argentina34 (Appendix 7).
Medications The mesalamine compounds were commonly used for CD, varying from 21.2% in Brazil35 to 100% in Cuba.36 High percentages of mesalamine use were noted in UC patients, from 56.36%19 to 100%.37 Use of mesalamine for CD patients in Brazil had fallen from 81.6% in 1970–199838 to 31.46% in 2013–2014,19 whereas use for UC patients fell from 93.2% in 1980–199910 to 56.36% in 2013–201419 (Appendix 8). Steroids were still widely used in the region, with percentages varying in CD and UC
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Figure 2. Prevalence. CD, Crohn’s disease; UC, ulcerative colitis.
from 13.3%39 to 87.5%.40 Immunomodulator use for CD patients in Brazil rose from 8.3% in 1970–199838 to 71.7% in 2013–2014,19 whereas use for UC patients rose from 5.4% in 1980–199910 to 19.4% in 2013–201419 (Appendix 8). Since approval of anti-TNF use in 2000, the proportion of patients with CD prescribed infliximab or adalimumab has risen steadily (Figure 4A, Appendix 8). For example, in Brazil, 29.6% of CD patients received anti-TNF from 2005 to 2012,41 rising to 43.4% in 2013–201419 (Figure 4A, Appendix 8). In contrast, the proportion of UC patients prescribed anti-TNF after 2006 remained consistently low. For example, only 4.5% of UC patients were prescribed anti-TNF in Brazil in 2013–201419 and 7% and 1.4% in Uruguay in 2016–201742 (Figure 4B, Appendix 8).
Hospitalization and Surgery Hospitalizations were highest in Colombia40 (CD, 75.0%; UC, 42.9%) and Peru43 (CD, 75.0%; UC, 51.8%) and lowest in Brazil, where CD hospitalization had fallen from 83.3% in 1980–199910 to 29.2% in 2006,44 and UC hospitalization had fallen from 63.0% in 1980–199910 to 43.8% in 2011–201245 (Appendix 9). Surgery for CD and UC steadily declined over time in several regions of Latin America: in Brazil from 1980–199910 (CD, 57.8%; UC, 21.9%) to 2016–201746 (CD, 31.7%; UC, 5.8%) and in Peru from 70.5% (CD) in 1990–201028 to 50.0% (CD) in 2004–201443 (Figure 4, Appendix 10). In contrast, the proportion of colectomy for UC remained stable in many regions: in Peru from 6.9% in 2001–200332 to 6.2% in 2004–201443 and in
Table 2. Prevalence per 100,000 Persons First author and publication year Sobrero 200923 Edwards 20088 Victoria 200911 Victoria 200911 Victoria 200911 Victoria 200911 Parente 201517 Lima-Martins 201819 Yepes-Barreto 201024 Juliao 201825 Vendrell 201326 Vendrell 201326 Vendrell 201326 Vendrell 201326
Country
Study period
IBD prevalence
CD prevalence
UC prevalence
Argentina Barbados Brazil Brazil Brazil Brazil Brazil Brazil Colombia Colombia Puerto Rico Puerto Rico Puerto Rico Puerto Rico
2007 2004 1988 1993 1998 2003 2012 2014 2006 2012 2002 2003 2004 2005
97.2 61.0 1.23 5.67 13.52 20.46 12.8 38.2 29 57.62 33.23 32.42 37.26 38.22
15.0 16.7 0.24 0.90 2.32 5.65
82.2 44.3 0.99 4.77 11.2 14.81
24.1 7 5.85 11.43 11.96 12.93 14.9
14.1 22 51.77 21.72 20.46 24.33 23.32
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Figure 3. UC:CD ratio. CD, Crohn’s disease; UC, ulcerative colitis.
Uruguay from 1951–200347 (UC, 8.3%) to 1985–201542 (UC, 10.5%) (Figure 4, Appendix 10).
Discussion Our systematic review identified significant gaps in high quality population-based studies of IBD in Latin America and the Caribbean. Nonetheless, the available data indicate notable heterogeneity between the countries that may be driven by factors such as historical colonization, culture, socioeconomic status, genetic background, lifestyle, and diet. Future studies should focus on developing large population-based registries that describe the epidemiology, natural history, and outcomes of IBD. Despite important variation in the incidence of both UC and CD in Latin America and the Caribbean, our review suggests that incidence has steadily increased during the past decades. In a descriptive review of the incidence and prevalence of IBD in Latin America, Farrukh and Mayberry9 speculated that epidemiologic patterns have mirrored the evolution of IBD in Spain during the 20th century. Historically, UC was diagnosed more commonly than CD in the Western world. During the 20th century, numerous studies confirmed a transition in the UC:CD ratio such that CD approximated the diagnosis of UC and in many Western countries became more common. Similar to the Western world, regions within Latin America that are associated with higher economic development, industrialization, and Westernization of environmental exposures (eg, diet) reported higher proportions of CD. Improved healthcare access and delivery may also influence the diagnosis of CD.
After decades of rising incidence, the prevalence of IBD has been expanding. Consequently, the prevalence of IBD in Latin America is equivalent to many countries in Asia and is approximating countries in Southern and Eastern Europe. As more individuals live with IBD, caring for these patients will exact a tremendous stress on the healthcare systems within Latin America and the Caribbean. Expansion of national registries of IBD is necessary for surveillance of the burden of IBD across these countries. Important variation in the prescription of medications was observed throughout the continent. The use of corticosteroids was high for both diseases. Moreover, the use of mesalamine compounds for CD is common, probably because of difficult access to biologics in some areas. The proportion of patients treated with anti-TNF therapy was also variable between the countries. Some studies demonstrated approximately 40% of biologic penetration for CD in more developed areas. Case series from other countries did not have such a high penetration, possibly because of difficulties in patient care, access to these agents, and the lack of specific local IBD study groups or associations that could increase the level of patient care. With the rising prevalence of IBD, countries in Latin America and the Caribbean can expect higher rates of hospitalization and surgeries and, in turn, greater utilization of expensive biologics to treat flares and prevent complications of IBD. Our review demonstrated an increase in the use of anti-TNF therapy in the management of CD, mostly after the approval of infliximab around the year 2000. In juxtaposition, surgery for CD decreased in the same period. Increased use of anti-TNF therapy for
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Figure 4. Proportion of patients with Crohn’s disease (A) and ulcerative colitis (B) prescribed anti-TNF therapy and undergoing an intestinal resection. CD, Crohn’s disease; TNF, tumor necrosis factor; UC, ulcerative colitis.
CD was likely related to greater disease awareness, better diagnostic techniques, and management strategies. In contrast, surgery rates for UC in the 21st century were relatively stable throughout Latin America. Similarly, the use of anti-TNF therapy for UC did not increase significantly in Latin American and Caribbean countries after 2006 when the ACT randomized controlled studies demonstrated the efficacy of infliximab in UC.48 These findings may be explained by difficulties in accessing anti-TNF therapies for UC, mostly on the basis of limited reimbursement from both public and private payors in many countries. As access to biologics expands and
increased awareness of therapeutic strategies for managing IBD (eg, less reliance on mesalamine for treatment of CD) rises, we can anticipate that rates of hospitalization and surgery will continue to fluctuate in this region of the globe. The major strength of our review was the inclusion of a local database (SciELO) in addition to MEDLINE and EMBASE. By including articles written in local languages, more data could be captured, and we believe this could be used as an example in methodology for future reviews in different parts of the world. This systematic review has some limitations that may influence the
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interpretation of our results. The information collected varied between studies, and data were based predominantly on cross-sectional studies. Most of the data were derived from tertiary centers from larger cities. Variables such as frequency of medication use, hospitalization, and surgery are described in crude values, with no defined follow-up. As the healthcare infrastructure in Latin American and Caribbean regions advances to include greater use of electronic administrative databases, a more complete picture of the health services and outcomes of IBD will become available. Furthermore, temporal trend analyses on incidence and prevalence of IBD were derived from a few population-based studies with sufficient longitudinal data, and thus extrapolation of the rising incidence and prevalence of IBD throughout Latin America and the Caribbean is an assumption that needs to be confirmed in future population-based studies. Finally, the quality assessment demonstrated that the majority of included studies were of low quality. For example, only 16 of the 61 studies were populationbased. Outcomes such as medication usage and surgery need to be interpreted cautiously and in the context of the limitation of including lower quality studies. Moreover, the paucity of high quality studies highlights an important gap in the literature and serves as a clarion call to invest in the infrastructure, resources, and personnel necessary to conduct non-biased observational research in Latin America and the Caribbean. In summary, this systematic review on the clinical and epidemiologic characteristics of IBD in Latin America and the Caribbean demonstrated that the incidence and prevalence of IBD may be increasing and that the UC:CD ratios are evolving throughout the continent. The phenotypes of IBD observed varied slightly between the countries but are consistent to what is seen in other parts of the world. The increase in the use of anti-TNF agents for CD may be correlated to a decrease in surgery; the same pattern was not observed in UC. This comprehensive systematic review outlines the important burden of IBD in Latin America and the Caribbean and emphasizes the need for better registries and populationbased studies in this region of the world.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at https://doi.org/10.1016/j.cgh.2019.06.030.
2. Ng SC, Shi HY, Hamidi N, et al. The worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017; 390:2769–2778.
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Acknowledgments G.G.K. is a CIHR Embedded Clinician Research Chair.
Q2
Conflicts of interest These authors disclose the following: Paulo Kotze has received consulting and speaker fees from AbbVie, Janssen, Pfizer, Takeda, and UCB. Aderson Damião has received consulting and speaker fees from AbbVie, Janssen, Pfizer, and Takeda. Rogerio Saad-Hossne has received consulting and speaker fees from AbbVie, Janssen, Pfizer, and Takeda. Martin Toro has received consulting and speaking fees from AbbVie, Janssen, and Takeda. Beatriz Iade has received consulting and speaking fees from AbbVie and Takeda. Fabio Vieira Teixeira has received consulting and speaking fees from AbbVie, Janssen, Ferring, and Takeda. Subrata Ghosh has received consulting fees from AbbVie, Janssen, Bristol-Myers Squibb, Pfizer, Celgene, and Boehringer-Ingelheim; served as a Scientific Advisory Board member for AbbVie, Janssen, and Takeda; and received research grants from AbbVie. Remo Panaccione has received consulting and speaker fees from AbbVie, Allergan, Celgene, Eli Lily, Ferring, Gilead, Janssen, Shire, and Takeda; served as a Scientific Advisory Board member for AbbVie, Allergan, Celgene, Eli Lily, Janssen, and Takeda; and received research grants from AbbVie, Janssen, and Takeda. Siew Ng has received consulting and speaker fees from AbbVie, Ferring, Janssen, Menarini, and Takeda; served as a Scientific Advisory Board member for AbbVie, Ferring, and Takeda; and received research grants from AbbVie, Ferring, and Janssen. Gilaad Kaplan has served as a speaker for Janssen, AbbVie, Takeda, and Pfizer; has received research support from Janssen, AbbVie, GlaxoSmith Kline, and Shire; and shares a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC, UTI Limited Partnership, assignee, Patent 62/555,397, 7 Sept 2017. The remaining authors disclose no conflicts.
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Q4 Funding Supported by Canadian Institutes of Health Research operating grant, funding Q10 reference number 162393.
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