Epidemiology of Inflammatory Bowel Disease in Mexico and Colombia PDF

RESEARCH ARTICLE Epidemiology of inflammatory bowel disease in Mexico and Colombia: Analysis of health databases, mathematical modelli...

RESEARCH ARTICLE Epidemiology of inflammatory bowel disease in Mexico and Colombia: Analysis of health databases, mathematical modelling and a case-series study Agustı́n Ciapponi1*, Sacha Alexis Virgilio ID1, Mabel Berrueta1, Natalie Claire Soto1, Álvaro Ciganda1, Moisés Freddy Rojas Illanes2, Briseida Rubio Martinez2, Johana Gamba3, Carlos Arturo González Salazar3, José Nicolás Rocha Rodrı́guez3, Bruno Scarpellini4, Ana Marı́a Bravo Perdomo5, Gerardo Machnicki6, Leandro Aldunate6, a1111111111 Juan De Paula7, Ariel Bardach1 a1111111111 1 Instituto de Efectividad Clı́nica y Sanitaria (IECS), Buenos Aires, Argentina, 2 Hospital Dr. Bernardo a1111111111 Sepúlveda, Mexico DF, Mexico, 3 Fundación Universitaria Sánitas, Bogotá, Colombia, 4 Janssen-Cilag a1111111111 Farmacêutica Ltda, São Paulo, Brazil, 5 Janssen-Cilag Farmacêutica Ltda, Bogotá, Colombia, 6 Janssen- a1111111111 Cilag Farmacêutica Ltda, Buenos Aires, Argentina, 7 Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina * [email protected] OPEN ACCESS Citation: Ciapponi A, Virgilio SA, Berrueta M, Soto Abstract NC, Ciganda Á, Rojas Illanes MF, et al. (2020) Epidemiology of inflammatory bowel disease in Mexico and Colombia: Analysis of health Background and aims databases, mathematical modelling and a case- series study. PLoS ONE 15(1): e0228256. https:// Ulcerative Colitis (UC) and Crohn’s Disease (CD) have a major impact on quality of life and doi.org/10.1371/journal.pone.0228256 medical costs. The aim of the study was to estimate the prevalence, incidence and clinical Editor: Valérie Pittet, Center for Primary Care and phenotypes of Inflammatory Bowel Disease (IBD) cases in Mexico and Colombia. Public Health, SWITZERLAND Received: July 11, 2019 Methods Accepted: January 12, 2020 We analyzed official administrative and health databases, used mathematical modelling to Published: January 27, 2020 estimate the incidence and complete prevalence, and performed a case-series of IBD patients at a referral center both in Mexico and Colombia. Copyright: © 2020 Ciapponi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which Results permits unrestricted use, distribution, and reproduction in any medium, provided the original The age-adjusted complete prevalence of UC per 100,000 inhabitants for 2015/2016 ranged author and source are credited. from 15.65 to 71.19 in Mexico and from 27.40 to 69.97 in Colombia depending on the model Data Availability Statement: All relevant data are considered. The prevalence of CD per 100,000 inhabitants in Mexico ranged from 15.45 to within the manuscript and its Supporting 18.08 and from 16.75 to 18.43 in Colombia. Information files. In Mexico, the age-adjusted incidence of UC per 100,000 inhabitants per year ranged Funding: This work was funded by Janssen-Cilag from 0.90 to 2.30, and from 0.55 to 2.33 in Colombia. The incidence for CD in Mexico ranged Pharmaceutical. Authors BS, AMBP, GM, and LA from 0.35 to 0.66 whereas in Colombia, the age-adjusted incidence of CD ranged from 0.30 received funding in the form of salaries from to 0.57. Janssen-Cilag Pharmaceutical. The specific roles of these authors are articulated in the ‘author The case-series included 200 IBD patients from Mexico and 204 patients from Colombia. contributions’ section. The funders had no role in The UC/CD prevalence ratio in Mexico and Colombia was 1.50:1 and 4.5:1 respectively. In PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 1 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia study design, data collection and analysis or Mexico, the female/male prevalence ratio for UC was 1.50:1 and 1.28:1 for CD, while in decision to publish. Colombia this ratio was 0.68:1 for UC and 0.8:1 for CD. In Mexico the relapse rate for UC Competing interests: This work was funded by was 63.3% and 72.5% for CD, while those rates in Colombia were 58.2% for UC and 58.3% Janssen-Cilag Pharmaceutical. This does not alter for CD. our adherence to PLOS ONE policies on sharing data and materials. In the synthesis of the main results of the study as well as in the development Conclusions of the writing of the manuscript did not interfere The estimated burden of disease of IBD in Mexico and Colombia is not negligible. Although any interest. In addition to this, the present study is of the epidemiological type, where the main results these findings need to be confirmed by population-based studies, they are useful for deci- are related to the estimation of prevalence and sion-makers, practitioners and patients with this condition. incidence of the disease, so we consider that it is still difficult for them to be influenced by interests outside those of the main researchers. There are no patents, products in development or marketed products evaluated in this research to declare. Introduction Inflammatory bowel disease (IBD) is a term encompassing two main inflammatory diseases of the colon and/ or small intestine: Crohn’s disease (CD) and Ulcerative Colitis (UC). Diag- nosis is based on clinical presentation, endoscopic findings and other imaging and histopatho- logic findings. Both diseases are chronic and clinically intermittent with remissions and relapses, possibly due to interactions between genetic and environmental factors. Differen- tiation between UC and CD is not always clear as symptoms overlap and extra-intestinal mani- festations can be similar. Treatment of inflammatory bowel disease includes lifestyle changes (e.g., smoking cessation for patients with CD), medical management, and surgical interven- tions. IBDs have a major impact on life expectancy, quality of life and medical costs. For example, patients with Crohn’s disease have a risk of dying over 50% higher than someone in the general population of the same age. IBD burden derives in an important increase of direct medical costs, although this may vary across countries. A Canadian study showed that IBD doubles healthy controls direct costs and that CD is on average 20% costlier than UC. Regarding UC, the cause of the disease is unknown; however, over-stimulation of an inade- quately regulated mucosal immune system appears to be a major pathophysiological pathway. The course of the disease is generally relapsing–remitting, with patients experiencing few or no gastrointestinal symptoms in between symptomatic flare-ups (relapses). The prevalence of UC in Europe and USA reaches 70–150 patients per 100,000 inhabitants. The overall mortality rates for CD have decreased around the world in the last twenty years, but based on recently published nationwide data there is still excess mortality during the disease course.[6,7] Mortality rates in CD vary in different regions of the world, that may be related with different genetic, environmental, and health care related conditions.[6,7] IBD’s epidemiology is well characterized in developed countries, but this is less so in Latin America (LA). However, a study reports that since 1990 IBD incidence has been rising in newly indus- trialized countries in South America and other regions. A systematic review including LA reported considerably lower prevalence rates for said region than for others and marked differences in the burden of the disease among countries. Environmental factors such as socio- economic status, exposure to infections, use of antibiotics and issues of hygiene, might help explain the epidemiological differences between populations. Some studies have attempted descriptions of the epidemiology of IBD in Latin America. [11–18] UC incidences ranged from 0.74 to 6.76 per 100,000 inhabitants, 0.24 to 3.50 for CD, and 0.42 to 2.46 for non-specified IBD. UC prevalence ranged from 0.99 to 44.3 per 100,000 inhabitants, 0.24 to 14.90 for CD and 0.42 to 38.22 for non-specified IBD. Some case-series PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 2 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia and descriptive studies also describe some features of these conditions in patients of LA. [19– 24] Despite the little evidence from the IBD patients in Latin America, our hypothesis is that the burden of disease in LA is not marginal. Considering this panorama of scarcity of epidemi- ological, clinical and resource use information, we aimed at conducting a study to estimate the prevalence, incidence and clinical phenotypes of IBD in Mexico and Colombia, two large countries of the region for which data is also lacking. Materials and methods We performed a retrospective observational study following the Strengthening The Reporting of Observational Studies in Epidemiology (STROBE) guidelines. During 2018, we included data from official administrative and health databases in Mexico and Colombia. We used the tenth revision of the International Classification of Diseases (ICD 10) IBD, selecting codes K50x (for CD) and K51x (for UC). We also explored related ICD codes, as K564: Other obstructions of the intestine, K63 Other diseases of the intestines, K638 Other specified dis- eases of the intestine, K639 Intestinal disease, unspecified, K591 Functional diarrhea, M075 Joint disease in ulcerative colitis, M095 Juvenile arthritis in ulcerative colitis and K529 Colitis and gastroenteritis not infectious, not specified. However, we decided not to include these additional codes because of their very low specificity. Because the capture-recapture approach requires the inclusion of health facilities serving at least 80% of the population from a geo- graphic area to estimate the target disease epidemiology with reasonable reliability, and this type of centers does not exist in Mexico and Colombia, we had to resort to alternative methods. We therefore analyzed official administrative databases, modelling incidence and prevalence with mathematical models. Mexico data As part of the process of estimation of prevalence and incidence of IBD cases in Mexico, which relate to the true burden of disease, we initially analyzed databases with information on hospi- tal discharges by IBD, sex and age group generated by the Mexican public health sector. Public sector discharge records were obtained from a standard-format database of hospital discharges in the health sector (2009–2015), which is available on the website of the National Health Information System (Sistema Nacional de Información en Salud—SINAIS) of the Gen- eral Directorate of Health Information (Dirección General de Información en Salud—DGIS). This database includes more than 40 million hospital discharge records during the evalu- ated period and provides basic information such as year of care, sex, age of patient, and main condition. The records are coded according to the ICD-10, length of stay, reason for dis- charge, and hospital discharges from the care institution, and have been compiled by the Min- istry of Health, the Mexican Social Security Institute (Instituto Mexicano del Seguro Social— IMSS), Oportunidades IMSS, the Institute for Social Security and Services for State Workers (Instituto de Seguridad Social y Servicios para Trabajadores del Estado—ISSSTE), PEMEX and the Mexican Navy (SEMAR). According to the Official Mexican Standard, hospital dis- charges information includes number of discharges due to cure, improvement, transfer to another hospital unit, death or discharge, and excludes transfers between different services within the hospital. It is important to consider that while hospital discharge records com- pile data for each event, a person can be admitted to the hospital on different occasions for the same cause or for various reasons in the same period. In order to capture this phenomenon, we used also the reported number of hospitalizations from the DGIS database. PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 3 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia For Mexico, the Population Council of Mexico (CONAPO) provided the population pro- jections data for different calendar years. The mortality data for the study period come from the General Directorate of Health Information (DGIS). Colombia data We obtained the number of patients with IBD as primary diagnosis from the Integral Informa- tion System of Social Protection (SISPRO) database. The SISPRO database, hosted by the Colombian Ministry of Health and Social Protection, offers consolidated data coming from all healthcare providers (hospitals and healthcare centers), which are obliged by law to report data using the ICD-10 coding for the primary diagnosis, for all registered persons who demand ser- vices within the Social Security Health System. It is considered that more than 90% of Colom- bians are registered with SISPRO. SISPRO does not provide information on IBD patients not reaching the healthcare system, and thus there is no available data about them. To estimate the yearly incidence, we considered a “new case” to be a person with a positive diagnosis not previously identified, who required Health Services for the first time and is recorded as an IBD patient for the first time in SISPRO. Official demographic information and vital statistics were obtained from the National Admin- istrative Department of Statistics (DANE). Prevalence of persons with IBD contacting the health system out of the total registered pop- ulation was used as a proxy of real prevalence. Incidence per 100.000 population-years was based on the annual frequency of new IBD cases contacting the health system. These contacts could be either emergency visits, ambulatory consultations and/or hospital discharges. Modelling We also used mathematical modelling to estimate the incidence and complete prevalence. Dis- Mod II model is a multistate life table that simulates the epidemiological progress of a single disease by exploiting the fact that parameters such as incidence, prevalence, remission, case fatality and mortality rates are not independent variables. Hence, it was designed to esti- mate epidemiological parameters on diseases when the availability of measured data is scarce. We used the Mexican and Colombian prevalence of the Institute of Health Metrics’ Global Burden of Disease project, estimated with Disease Modeling Multiregression (DISMOD-MR) as our input for the DISMOD II model for the years 2010 and 2016, for which data was avail- able., We assumed zero remission rate. We also ran MIAMOD, a model originally developed for cancer complete prevalence esti- mates[36,37]. It uses a back-calculation method that could be applied to estimate the incidence and complete prevalence of IBD, as a chronic condition, from specific age-gender mortality and survival as inputs. Mortality came from DGIS, and survival was extrapolated from Danish IBD cases, being Denmark a country with extensive high-quality surveillance informa- tion. Regarding the degree of coverage of mortality data we used WHO’s Global Health Obser- vatory. Mortality input values for models were adjusted for this type of under-reporting, which was 5.5% for Mexico and 6% for Colombia, according to UN tables. In order to esti- mate complete prevalence figures with MIAMOD we performed a sensitivity analysis consid- ering an additional correction of 10%, due to garbage coding, anticipating that this is the model that provides the upper limit estimations. Cases-series Regarding clinical phenotypes of disease, during 2018 we chose two centers: Hospital Dr. Ber- nardo Sepúlveda, Colorectal surgery Department, in Mexico City, Mexico; and Clı́nica PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 4 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia Universitaria Colombia–EPS Sánitas in Bogotá, Colombia. Those centers collected retrospec- tively a case-series of patients under clinical follow-up. These large referral centers included both outpatients and inpatients, and the diagnosis of IBD was established according to the most updated diagnostic recommendations for IBD. This included clinical features, endoscopy of the colon, other biochemical and imaging procedures like video capsule or pan-endoscopy, and biopsy. The date of IBD diagnosis was considered the starting point of the disease follow- up, and the symptoms onset date was recorded separately. We gathered demographic data of patients, family history of IBD, disease anatomical extension, severity of disease at the time of diagnosis, signs and symptoms, hospitalization episodes, relapse dates, and treatment patterns. We used a sample of 200 consecutive cases from the routine database of the clinic cases that allow ±5% of semi-amplitude of the 95% confidence interval for the proportions of those least frequent symptoms. Univariate statistical analyses were performed to outline the study popula- tion. Wilcoxon test and X2 tests were done to determine differences in continuous and cate- gorical variables, respectively. Dependent variable, UC clinical remission, was analyzed according to the main variables collected, through a multivariable regression analysis. We pre- sented central estimations with their 95% confidence Intervals (CI), both in tables and in graphical format. We performed these analyses using Stata statistical software (v. 14.1, Stata- Corp, College Station, TX). The study was approved by the Ethics Committee of the Instituto Mexicano del Seguro Social (IMSS), Ref. 09-B5-61-2800/201800 and by the Research Ethics Committee of the Fun- dación Universitaria Sanitas, Bogotá Colombia, Act 017–18. Results Epidemiology in Mexico Data from Mexican administrative databases allowed us to present discharge rates by IBD but did not allow us to estimate incidence or prevalence of disease. In S1 and S2 Files, we present the overall and by-age group rates per 100,000 population of hospital discharges by IBD type and sex, and the discharge rates by age groups from 2010 to 2015 to complement our epidemi- ological estimates based on SINAIS data. We present the results using mathematical modelling (DISMOD II AND MIAMOD) to estimate the incidence and complete prevalence. The age-adjusted complete prevalence of UC per 100,000 inhabitants for 2015/2016 ranged from 15.65 to 71.19, depending on the model considered. The prevalence of CD per 100,000 inhabitants, ranged from 15.45 to 18.08. The age-adjusted incidence of UC per 100,000 inhabi- tants per year, ranged from 0.90 to 2.30, and for CD ranged from 0.35 to 0.66 using both mod- els. The prevalence by sex for 2010 and 2015/2016 is presented in Table 1. The MIAMOD adjusted prevalence was twice as high as the DisMod II for men and six times the value for females, and regarding CD they were quite similar. The MIAMOD adjusted was 1.5 and three times higher than the DisMod II in male and female UC incidence, respectively. We found similar female CD incidence and around two times higher for males (Table 1). The female-male ratio for UC prevalence was 2.1: 1 and for the CD prevalence was 0.8:1 (MIAMOD) and 0.7:1 and 1:1 using DisMod II. Epidemiology in Colombia We collected information of the years 2010–2015 from SISPRO, the most complete from the database inception. We found a total of 51,330 people who consulted with the Colombian Health System between 2010 and 2015. These people visited different centers whose data are PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 5 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia Table 1. Mexico 2010–16. Comparison of complete population prevalence and incidence rates of total IBD, as modelled by DisMod II and MIAMOD for the years 2010 and 2015/16. Outcomes Years Ulcerative Colitis Crohn’s Disease Male Female Male Female DisMod II† MIAMOD DisMod II†† MIAMOD DisMod II# MIAMOD DisMod II## MIAMOD Base +10% Base +10% Base +10% Base +10% Prevalence 2010 19.20 39.80 43.90 17.79 84.08 98.30 21.16 18.15 20.02 16.71 14.63 16.09 2015/16 17.00 39.84 43.95 14.3 84.20 98.43 20.50 18.16 20.05 10.40 14.65 16.11 Incidence 2010 1.00 1.41 1.55 0.68 2.65 3.05 0.30 0.68 0.75 0.30 0.52 0.57 2015/16 1.00 1.41 1.55 0.80 2.65 3.05 0.30 0.68 0.75 0.40 0.52 0.57 Prevalence inputs based on DISMOD-MR , † 22 (2010) and 21 (2016) †† 16 (2010) and 15 (2016) # 13 (2010) and 12 (2016) ## 10 (2010) and 8.4 (2016). Results from MIAMOD with an adjusted of 10% in the specific mortality data; NE: Not Estimated. https://doi.org/10.1371/journal.pone.0228256.t001 submitted to the SISPRO registry. Table 2 shows the information from this database, present- ing the yearly number of people who have been admitted to hospitals, who have used the emer- gency services and who have received medical procedures due to inflammatory bowel disease at the outpatient setting. The frequency of drugs prescriptions in patients with IBD came from a sub-database of SIS- PRO including 837 patients who received specific IBD medication during the period 2010 to 2015. There was no data available for the calendar year 2012. About 72% (n = 599) received azathioprine while 56% (n = 469) and 36% (n = 305) received mesalazine and steroids, respectively. According to our results, in Colombia the age-adjusted complete prevalence of UC per 100,000 inhabitants for 2015/2016 ranged from 27.40 to 69.97 depending on the model consid- ered. The prevalence of CD per 100,000 inhabitants, ranged from 16.75 to 18.43. The age- adjusted incidence of UC per 100,000 inhabitants per year, ranged from 0.55 to 2.33, and for CD ranged from 0.30 to 0.57, respectively. These estimations were very similar to the 2010 esti- mations. The separate estimations by gender are presented in Table 3. The MIAMOD adjusted complete prevalence was 2 to 3 times higher than the DisMod II prevalence for UC and from 0.7 to 1.4 for CD. The MIAMOD adjusted incidence was 2 to 3 times higher than the DisMod Table 2. Colombia 2010–15. Number of hospital discharges, emergency and outpatient visits, by IBD type and sex (all ages). Year Ulcerative Colitis Crohn’s Disease Males Females Males Females Hospital Emerg. Outp. Hospital Emerg. Outp. Hospital Emerg. Outp. Hospital Emerg. Outp. 2010 137 129 3003 181 185 4166 20 25 487 10 23 801 2011 182 201 3639 252 266 4858 30 43 527 25 39 736 2012 211 280 4013 248 364 5355 39 53 526 38 65 643 2013 189 326 4190 217 395 5614 32 48 520 21 56 733 2014 224 385 4655 254 535 6291 43 58 603 32 67 796 2015 211 253 4124 268 342 5689 45 34 501 37 49 643 Source: SISPRO database https://doi.org/10.1371/journal.pone.0228256.t002 PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 6 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia Table 3. Comparison of complete population prevalence and incidence rates of UC and CD as modelled by DisMod II and MIAMOD for Colombia in the years 2010 and 2015/6, and from SISPRO. Outcomes Years Ulcerative Colitis Crohn’s Disease Male Female Male Female SISPRO DisMod II† MIAMOD SISPRO DisMod II†† MIAMOD SISPRO DisMod II# MIAMOD SISPRO DisMod II## MIAMOD Base +10% Base +10% Base +10% Base +10% Prevalence 2010 16.76 16.57 47.79 52.36 21.8 19.24 79.27 87.2 2.73 19.29 12.89 14.17 4 15.38 20.58 22.64 2015/6 20.25 26.6 47.85 54.3 26.72 28.2 79.39 87.33 2.56 20.2 12.9 14.19 3.1 16.6 20.61 22.68 Incidence 2010 13.7 0.81 1.69 1.86 18.4 0.48 2.52 2.81 2.6 0.31 0.44 0.48 3.9 0.29 0.61 0.7 2015/6 13.5 0.7 1.69 1.86 18.8 0.4 2.48 2.81 1.6 0.3 0.43 0.48 2.1 0.3 0.60 0.7 Prevalence inputs based on DISMOD-MR34,35 †19 (2010) and 19 (2016) ††15 (2010) and 14 (2016) #12 (2010) and 12 (2016) ##9.7 (2010) and 8.7 (2016). Results from MIAMOD with an adjusted of 10% in the specific mortality data; NE: Not Estimated. https://doi.org/10.1371/journal.pone.0228256.t003 II incidence for UC (although seven times higher for females) and from 1.6 to 2.3 times higher for CD. Regarding the comparison with SISPRO, the MIAMOD adjusted prevalence was 3 to 4 times higher than the cumulative proportion of UC patients registered in SISPRO, and 5 to 7 times higher for patients affected of CD. In the S2 File we show the prevalence of IBD by sex and age group estimated using the MIAMOD model base case for both countries. The S1 File show the Colombian prevalence of UC and CD among health system users by age group from 2010 to 2015. Case-series We recruited 404 IBD patients from Mexico D.F and Bogota City. The case-series in Mexico included a total of 200 patients with a diagnosis of IBD, 120 individuals had UC (60%) and 80 patients had CD (40%). The UC/CD ratio was 1.5: 1. The female-male ratio in UC was 1.5: 1 (60% vs 40%), and the CD ratio was 1.28: 1 (56.25% vs 47.75%). The Colombian case-series included a total of 204 patients with a diagnosis of IBD, 165 individuals had UC (80.88%), 36 patients had CD (17.65%) and 3 patients had an unclassifiable type of IBD (1.47%). The UC/ CD ratio was 4.5:1. The female/male ratio in UC was 0.68:1 (40.61% vs 59.4%), and 0.8:1 (44.44% vs 55.56%) for CD. See Table 4. Table 5 shows the most frequent clinical manifestations in IBD patients in both countries. The most frequent symptoms in both case-series were diarrhea, rectal bleeding and abdominal pain. Table 6 shows the prevalence ratio of the clinical manifestations in IBD patients of both cases-series. In Mexico, anorexia and weight loss were the clinical features most significantly related with UC, while abdominal pain was the symptom most frequently associated with CD. In relation with Colombian patients, bleeding was the clinical feature most significantly related with UC, while weight loss, abdominal pain, bowel obstruction and arthritis were the signs/ symptoms most associated with CD. Diarrhea is equally prevalent in both pathologies. Among Mexican patients, the most frequent anatomical involvement in CD patients were ileocolonic (37%) and colonic (30%) while the most frequent anatomical localization of UC patients was pancolitis with 55.83%, while left-sided colitis and proctitis were 34.17% and 10%, respectively. In Colombia, the most frequent anatomical involvement in CD patients were ileo-terminal (55%) and ileocolonic (39%), while the most frequent anatomical localization of UC patients was pancolitis with 39%, left-sided colitis 33.5% and proctitis 27.5%. PLOS ONE | https://doi.org/10.1371/journal.pone.0228256 January 27, 2020 7 / 17  Epidemiology of inflammatory bowel disease in Mexico and Colombia Table 4. Clinical characteristics of UC and CD patients in the case-series of patients in Mexico City (n = 200) and Bogota (n = 204). Mexico Colombia Characteristics Ulcerative Crohn’s p Ulcerative Crohn’s Non- p Colitis Disease Colitis Disease specific (n = 120) (n = 80) (n = 165) (n = 36) (n = 3) Women n (%) 72 (60) 45 (56.25) 0.59 67 (40.6) 16 (44.4) 2 (66.7) 0.62 Ever smoker (%) 50 (41.6) 42 (52.5) 0.44 35 (21) 8 (22) - 0.55 # Age at diagnosis— 40 (28.5–49.5) 49.5 (30.5– 0.03 38 (12–80) 49 (12–85) 51 (25–68) 0.14# median (min-max) 61.5) Symptoms starting age 38 (26.5–49) 49 (29.5–60) 0.01# 37 (11–80) 47 (11–84) 51 (23–68) 0.17# —median (min-max) Time to diagnosis— 0 (0–1) 0.5 (0–2) 0.1# 0 (0–11) 0.5 (0–2) - 0.39# median years (min- max) X2 tests # Test U of Mann-Whitney. https://doi.org/10.1371/journal.pone.0228256.t004 At time of data collection, the most frequent clinical condition in Mexican UC patients was clinical remission (83%), followed by mild and moderate compromise (14% and 3% respec- tively). Out of 102 of patients in remission, 100 presented clinical remission, 68 biochemical remissions, 63 presented endoscopic remission and 28 patients presented histopathological remission. In Colombia, 58% of UC patients presented clinical remission, 26% being mild, and 16% moderate in the category of severity. In the Mexican case-series, the relapse rate of the IBD patients was 67% (134/200). The UC relapse rate was 63.33% (n = 76), while the CD relapse rate was 72.5% (n = 58) without statis- tics difference (p = 0.15). In comparison, in the Colombian case-series the relapse rate for IBD was 57.4% (117/204); 58.2% in UC patients (96/165), and 58.3% in CD ones (21/36). Table 5. Clinical signs and symptoms observed in IBD case-series of patients in both countries. Mexico (n = 200) Colombia (n = 201) Clinical signs and Ulcerative Colitis Crohn’s Disease p Ulcerative Colitis Crohn’s Disease p symptoms (n = 120) (n = 80) (n = 165) (n = 35) Diarrhea n(%) 118 (98.50) 72 (90.00) 0.01 151 (91.5) 31 (86.1) 0.85 Rectal bleeding n(%) 119 (99.20) 72 (90.00) 0.01 147 (89.1) 24 (67.7) 0.01 Abdominal Pain n 92 (77.00) 32 (40.00) 0.06 127 (77) 32 (88.9) 0.1 (%) Weight Loss n(%) 43 (35.83) 52 (65.00)