Incidence, and natural history of inflammatory bowel disease in Castilla y León:Prospective and multicenter epidemiological study | Gastroenterología y Hepatología (English Edition)

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which is influenced by environmental factors in genetically predisposed individuals&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and their incidence is increasing globally&#44; particularly in western countries &#40;USA&#44; Canada&#44; Australia&#44; New Zealand and Western Europe&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> coinciding with population growth and industrial and economic development&#44; with prevalence figures of 1 in 200&#8211;300 inhabitants in developed countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> Meanwhile&#44; new cases of IBD are appearing in developing countries&#44; where the presence of these diseases was non-existent&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Spain is the country that has published the largest number of prospective and population-based incidence studies&#44; with figures similar to those reported in the rest of the European countries &#40;5&#8211;12 cases of UC&#47;100&#44;000 inhabitants&#47;year and 3&#46;5&#8211;9&#46;5 cases&#47;100&#44;000 inhabitants&#47;year for patients with CD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Our primary objective was&#44; based on the data collected prospectively at the national level for the EPIDEM-IBD registry that has just been published&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> to calculate the incidence of IBD in the community of Castile and Le&#243;n&#46; Our secondary objectives were to describe the clinical characteristics of the patients at diagnosis&#44; to evaluate the type of treatment received &#40;immunosuppressive and&#47;or biologic drugs and surgery&#41;&#44; as well as the clinical course during the first year of disease progression from diagnosis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A prospective&#44; multicentre&#44; population-based study including all patients over 18 years of age diagnosed with IBD &#40;CD&#44; UC or IC&#41; from 1 January 2017 to 31 December 2017 in the autonomous community of Castile and Le&#243;n&#44; with the participation of eight hospitals from five provinces of the community &#40;Valladolid&#58; Hospital Universitario R&#237;o Hortega &#91;R&#237;o Hortega University Hospital&#93;&#44; Hospital Cl&#237;nico Universitario &#91;University Clinical Hospital&#93; and Hospital Medina del Campo &#91;Medina del Campo Hospital&#93;&#59; Burgos&#58; Hospital Universitario &#91;University Hospital&#93; and Hospital Santos Reyes de Aranda de Duero &#91;Santos Reyes de Aranda de Duero Hospital&#93;&#59; Complejo Asistencial Universitario de Le&#243;n &#91;Le&#243;n University Healthcare Complex&#93;&#44; Hospital Universitario de Salamanca &#91;Salamanca University Hospital&#93; and Hospital Virgen de la Concha &#91;Virgen de la Concha Hospital&#93; in Zamora&#41;&#44; with a total population of 1&#44;745&#44;988 inhabitants in that year and a mean follow-up of nine months &#40;range 8&#8722;11&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In Spain&#44; the health system is public&#44; with only 15&#37; of patients having private insurance&#44; and of these&#44; only 15&#37; do not use the public system&#44; so it was decided at the national level not to include these patients&#44; given that they would not significantly modify the incidence results&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Incident cases of IBD in the different hospitals were included prospectively&#44; checking the endoscopy&#44; pathology and radiology databases in order to avoid losing cases&#46; Subsequently&#44; a visit was made at three months and at one year&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The following variables were collected using <span class="elsevierStyleItalic">Research Electronic Data Capture &#40;REDCap&#41;</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> with the permission of the Spanish Association of Gastroenterology &#40;<a href="http://www.aegastro.es">www&#46;aegastro&#46;es</a>&#41;&#44; a non-profit society&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Sex and age&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Diagnosis of IBD following the guidelines of the European Crohn&#39;s and Colitis organisation &#40;ECCO&#41; and the European Society of Gastrointestinal and Abdominal Radiology &#40;ESGAR&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Phenotype and extension according to the Montreal classification&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Time elapsed until diagnosis&#58; time from the patient&#39;s first symptomatic consultation with their doctor until the diagnosis was established&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Smoking habit&#58; a smoker was defined as a patient who smoked more than seven cigarettes a week for at least six months prior to diagnosis and had smoked at least one cigarette in the six months prior to diagnosis&#59; an ex-smoker was a patient who had stopped smoking for at least six months prior to diagnosis&#44; and a non-smoker was a patient who had never smoked or only smoked very sporadically&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">First-degree family history of IBD&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Prior appendectomy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Extraintestinal manifestations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Pharmacological treatments received since IBD diagnosis&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">o</span><p id="par0085" class="elsevierStylePara elsevierViewall">Mesalazine&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">o</span><p id="par0090" class="elsevierStylePara elsevierViewall">Corticosteroids&#58; systemic&#44; topical or rectal&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">o</span><p id="par0095" class="elsevierStylePara elsevierViewall">Immunosuppressive drugs&#58; azathioprine&#44; mercaptopurine and methotrexate&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">o</span><p id="par0100" class="elsevierStylePara elsevierViewall">Biologics&#58; infliximab&#44; adalimumab&#44; ustekinumab&#44; and vedolizumab&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Surgery at diagnosis or during follow-up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">Hospitalisation and reasons for admission&#46;</p></li></ul></p><p id="par0115" class="elsevierStylePara elsevierViewall">To carry out the statistical analysis&#44; the data was processed using the statistical software IBM SPSS 22&#46; A descriptive analysis of the sample was performed&#44; providing medians &#40;interquartile range&#41; and frequency &#40;percentage&#41; according to the type of variable&#46; A comparative analysis was carried out between both diseases &#40;UC vs&#46; CD&#41;&#44; evaluating epidemiological and clinical data and types of treatment&#46; Depending on the type of variables&#44; either the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test or the chi-square test &#40;Fisher&#41; were used&#46; To calculate the incidence per 100&#44;000 inhabitants&#44; data from the National Statistics System were used for the reference population&#44; using this data as the denominator&#46; In addition&#44; the age-standardised rate adjusted to the European population was calculated&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0120" class="elsevierStylePara elsevierViewall">During the inclusion period &#40;12 months&#41; a total of 290 patients were diagnosed with IBD&#46; Of these&#44; 158 patients &#40;54&#46;5&#37;&#41; were diagnosed with UC&#44; 131 &#40;45&#46;2&#37;&#41; with CD and one &#40;0&#46;3&#37;&#41; with IC&#44; with a median follow-up of nine months &#40;range 8&#8211;11 months&#41;&#59; 51&#37; were male &#40;147&#41;&#44; with a mean age of 47 years &#40;33&#8211;58&#41;&#46; The epidemiological data are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">The IBD <span class="elsevierStyleItalic">incidence rate</span> in Castile and Le&#243;n in 2017 was 16&#46;6 cases&#47;100&#44;000 inhabitants-year &#40;9&#47;10<span class="elsevierStyleSup">5</span> cases of UC and 7&#46;5&#47;10<span class="elsevierStyleSup">5</span> cases of CD&#41;&#44; with a UC&#47;CD ratio of 1&#46;2&#58;1&#46; The incidence in patients older than 65 years was 7&#46;9&#47;10<span class="elsevierStyleSup">5</span> &#40;5&#47;10<span class="elsevierStyleSup">5</span> cases of UC and 2&#46;9&#47;10<span class="elsevierStyleSup">5</span> cases of CD&#41;&#46; These incidence rates are shown in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;3</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The extension at diagnosis</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; in patients with UC was 37&#37; proctitis &#40;E1&#41;&#44; 31&#37; left-sided colitis &#40;E2&#41; and 32&#37; extensive colitis &#40;E3&#41;&#46; In CD&#44; 60&#37; presented involvement in the terminal ileum &#40;L1&#41;&#44; 16&#37; colonic involvement &#40;L2&#41; and 23&#37; ileocolonic involvement &#40;L3&#41;&#46; Seven patients &#40;5&#37;&#41; presented involvement of the upper digestive tract &#40;L4&#41; and 12 patients &#40;9&#37;&#41; had concomitant perianal disease&#46; The phenotype at diagnosis of CD was mostly inflammatory &#40;B1&#41; &#40;84&#37;&#41;&#44; in 17 patients it was stenosing &#40;B2&#41; &#40;13&#37;&#41; and in four patients it was fistulising &#40;B3&#41; &#40;3&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">median delay from symptom onset to diagnosis</span> was two months &#40;range 1&#8722;6 months&#41;&#46; The family association was 14&#37;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Among active <span class="elsevierStyleItalic">smokers</span> &#40;72 patients&#41; more than 69&#37; had CD&#44; while among ex-smokers &#40;98 patients&#41; most &#40;77&#37;&#41; were diagnosed with UC&#44; these differences being statistically significant &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#46; At the time of diagnosis&#44; 30 patients &#40;10&#37;&#41; had extraintestinal manifestations&#44; more frequent in CD&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Regarding the <span class="elsevierStyleItalic">medical treatment</span> established during follow-up from the time of diagnosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">-</span><p id="par0150" class="elsevierStylePara elsevierViewall">One hundred and seventy-one patients &#40;59&#37;&#41; received <span class="elsevierStyleItalic">salicylates</span> &#40;oral and&#47;or topical&#41;&#58; almost all &#40;96&#37;&#41; of the patients with UC and 14&#37; of patients with CD&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">A total of 177 patients &#40;61&#37;&#41; received <span class="elsevierStyleItalic">corticosteroid therapy</span> in its different forms &#40;systemic&#44; topical oral or rectal&#41;&#44; 103 patients &#40;58&#37;&#41; in the CD group and 74 patients &#40;42&#37;&#41; in the UC group&#46; Of the total number of patients treated with corticosteroids&#44; 109 patients &#40;62&#37;&#41; received them systemically &#40;orally or intravenously&#41;&#44; 55 patients &#40;31&#37;&#41; received topical oral treatment and 13 &#40;7&#37;&#41; topical rectal treatment&#46; Significantly more CD patients &#40;47&#37;&#41; received systemic corticosteroids&#44; compared to 30&#37; of UC patients &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; These differences were also significant when comparing the use of topical corticosteroids &#40;30&#37; vs&#46; 10&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41; between patients with CD and those with UC&#46; However&#44; the use of rectal corticosteroids was significantly more frequent in patients with UC &#40;7&#37; vs&#46; 2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0026&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Immunomodulatory therapy</span> was used in a total of 86 patients &#40;30&#37;&#41;&#44; being more frequently used in patients with CD &#40;81&#37;&#41; than in patients with UC &#40;19&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding <span class="elsevierStyleItalic">biologic treatment</span>&#44; significantly more patients with CD &#40;29&#37;&#41; required biologic therapy compared to patients with UC &#40;8&#37;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#44; with anti-TNFs being the drugs mostly used &#40;48 patients &#91;17&#37;&#93;&#41;&#44; while four patients received vedolizumab &#40;1&#46;4&#37;&#41; and one patient received ustekinumab &#40;0&#46;3&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0170" class="elsevierStylePara elsevierViewall">Seventeen patients &#40;6&#37;&#41; required <span class="elsevierStyleItalic">surgery</span> at diagnosis or during follow-up&#58; nine patients &#40;53&#37;&#41; in the abdominal region &#40;resection of the small intestine and&#47;or colon&#44; total proctocolectomy with anastomosis or ileostomy&#41;&#44; and eight patients &#40;47&#37;&#41; in the perianal region &#40;abscess drainage&#44; seton and fistula treatment&#41;&#46; The need for surgery was greater in patients with CD &#40;11&#37;&#41; than in patients with UC &#40;2&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">The overall <span class="elsevierStyleItalic">hospitalisation rate</span> was 26&#37; &#40;76 patients&#41;&#58; 44 &#40;58&#37;&#41; of the patients with CD and 32 patients &#40;20&#37;&#41; with UC&#46; The most common cause was admission at diagnosis &#40;64&#37;&#41;&#44; followed by flare-up &#40;29&#37;&#41;&#44; other causes &#40;16&#37;&#41;&#44; obstruction &#40;5&#37;&#41;&#44; adverse drug effects &#40;4&#37;&#41;&#44; infections &#40;3&#37;&#41; and perianal disease &#40;1&#37;&#41;&#46; When analysing hospitalisation due to a clinical flare-up of the disease &#40;22 patients&#41;&#44; more UC patients &#40;72&#37;&#41; were admitted than CD patients &#40;27&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the comparative study between the different variables of patients with CD and UC&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0185" class="elsevierStylePara elsevierViewall">In recent decades&#44; the incidence rates of IBD have been progressively increasing worldwide&#44; in parallel with the industrial development of certain countries in Asia&#44; Africa&#44; South America and Eastern Europe&#44; although prospective data are scarce and almost all come from retrospective data&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> In Shivananda&#39;s study of the north-south incidence in Europe for the years 1990&#8211;1993&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> a difference in incidence was reflected in favour of the countries of northern Europe&#44; both for UC and CD&#44; a difference that has currently been transferred to the east-west comparison&#44; as reflected in the 2010 data from the European ECCO-EpiCom study&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Compared to other European countries&#44; Spain had similar rates&#44; with an incidence of 9&#46;4&#47;10<span class="elsevierStyleSup">5</span> for UC and 10&#46;8&#47;10<span class="elsevierStyleSup">5</span> for CD&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> although it should be noted that only one Spanish centre from Galicia participated in this European study&#46; Over time&#44; new studies published in different parts of Spain &#40;Oviedo&#44; Madrid and Navarre&#41; have shown this increase in the overall incidence of IBD in Spain&#44; approaching the incidence described in northern European countries &#40;5&#8211;12&#47;10<span class="elsevierStyleSup">5</span> for UC and 3&#46;5&#8211;9&#46;5&#47;10<span class="elsevierStyleSup">5</span> for CD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4&#44;7</span></a> This study presents the first prospective data from an incident cohort of IBD in Castile and Le&#243;n with incidence rates similar to the highest reported in our country for patients with UC &#40;9&#47;10<span class="elsevierStyleSup">5</span> cases&#41;&#44; but lower for patients with CD &#40;7&#46;5&#47;10<span class="elsevierStyleSup">5</span> cases&#41;&#46; This stability in the incidence of CD coincides with the rest of the Spanish regions that participated in the EPIDEM-IBD study&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The female&#47;male ratio for our IBD patients was 0&#46;97&#44; with a slight predominance of males in UC&#44; but without statistical significance&#46; The various published studies seem to agree that gender does not influence the incidence of IBD&#46; Our data are within what has been described in the literature so far&#46; However&#44; a recent population study from the Asia-Pacific area shows that there is a predominance of the male sex in both IBD types at all ages&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The clinical phenotypes and disease course of the subjects in our cohort were similar to those described in the latest prospective studies published&#44; with a higher percentage of proctitis &#40;37&#37;&#41; compared to the European series &#40;20&#8211;21&#37;&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> which probably reflects an exhaustive search for cases&#44; due to our study design&#44; which are often missed in tertiary hospitals&#46; We also observed a lower percentage of high involvement &#40;L4&#41; in patients with CD &#40;5&#37;&#41; compared to percentages of 10&#8211;15&#37;&#44; which is probably explained by the lack of early routine study of the upper tract in newly diagnosed patients with CD&#44; and the short follow-up interval &#40;one year&#41;&#46; Although in the classic series<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> the onset of patients with CD and an inflammatory pattern is approximately 80&#37;&#44; the Spanish data from the EpiCom study<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> demonstrate a lower percentage &#40;66&#8211;68&#37;&#41;&#46; Our data are closer to the classic series with a baseline percentage for the inflammatory pattern of 84&#37;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">In our incident cohort&#44; the use of salicylates was practically the norm in patients with UC&#44; but we must point out that up to 15&#37; of patients with CD were treated with salicylates&#44; which confirms the resistance to change from a classic attitude in previous decades&#44; since the evidence of the efficacy of salicylates in patients with CD is very low<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and their use in this scenario is currently not recommended by clinical guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Regarding the natural history&#44; globally the patients with CD in our incident cohort presented a worse clinical course than the patients with UC&#44; evaluated by a greater consumption of corticosteroids&#44; immunomodulators&#44; biologics and surgery during the first year after diagnosis&#44; with statistically significant differences&#44; data that confirm what was published in previous European cohorts&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The need for hospitalisation in IBD patients is common due to disease flare-ups&#46; Specifically in patients with UC&#44; a hospitalisation rate of 23&#37; has been described in the Epi-IBD study at five years&#44; being higher in western countries than in eastern ones&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> In the systematic review of population studies&#44; published in 2018&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> the percentage of admissions in patients with UC was 17&#8211;29&#37; per year&#46; In our cohort&#44; the percentage of admissions for patients with UC was 20&#37;&#44; and although the overall number of admissions was numerically higher in patients with CD &#40;56&#37;&#41;&#44; it is noteworthy that admissions due to a disease flare-up were statistically more frequent in patients with UC &#40;23&#37;&#41; than in patients with CD &#40;8&#37;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">It has been described that the percentages of surgery in patients with UC and CD have remained stable during the last decades&#44; with figures similar to those reported in our cohort during the first year &#40;2&#37; in UC and 11&#37; in CD&#41;&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">The greatest strength of our study is that it is a population-based and prospective study that included different tertiary and regional hospitals with exhaustive methodology&#44; and it reflects the current incidence rates of patients with IBD in our community of Castile and Le&#243;n&#46; A weakness&#44; perhaps&#44; is the short follow-up &#40;nine months on average&#41; of the patients&#44; although the data from the national study will be published with a five-year follow-up&#44; in which patients from our community are included&#46; However&#44; our results are consistent with those published in other countries with the same follow-up period&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0225" class="elsevierStylePara elsevierViewall">The incidence of patients with UC in our setting is increasing&#44; while that of CD remains stable&#44; with higher requirements in terms of the use of corticosteroids&#44; immunosuppressants&#44; biologics and surgery for patients with CD compared to patients with UC in the first year of follow-up&#44; which indirectly translates into a worse natural history for these patients&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0230" class="elsevierStylePara elsevierViewall">Financial support for the logistics and coordination of the research of the study at the national level through a FIS &#40;Health Research Fund&#41; grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Carlos III Institute</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">PI16&#47;01296</span> and <span class="elsevierStyleGrantNumber" refid="gs0005">PFI17&#47;00143</span>&#41;&#44; <span class="elsevierStyleGrantSponsor" id="gs0010">GETECCU</span> &#40;Spanish Working Group on Crohn&#39;s Disease and Ulcerative Colitis&#41; and <span class="elsevierStyleGrantSponsor" id="gs0015">MSD</span>&#44; without having any role in the design of the study&#44; analysis and interpretation of data&#44; drafting of the manuscript or in the decision to publish it&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0235" class="elsevierStylePara elsevierViewall">Dr R&#46; S&#225;iz&#58; support for training activities for Jannsen&#44; Ferring and Gilead&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Dr J Barrio&#58; has served in speaking or consulting roles and has received research or educational funding from MSD&#44; AbbVie&#44; Takeda&#44; Janssen and Ferring&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Dr L&#46; Fern&#225;ndez-Salazar&#58; support for research and&#47;or training activities for Tillots Pharma&#44; Janssen and Takeda&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Dr L&#46; Arias&#58; scientific advice&#44; support for research and&#47;or training activities for AbbVie&#44; FAES Pharma&#44; Kern Pharma&#44; Ferring and MSD&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Dr M&#46; Sierra Aus&#237;n&#58; has received fees for training activities&#44; research support and advisory services for Takeda&#44; Janssen&#44; MSD&#44; AbbVie&#44; Pfizer&#44; Ferring and Falk&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Dr C&#46; Pi&#241;ero&#58; scientific advice&#44; support for research and&#47;or training activities for AbbVie&#44; FAES Pharma&#44; Janssen&#44; Ferring&#44; Pfizer and Takeda&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Dr A&#46; Fuentes Coronel&#58; support for research and&#47;or training activities for AbbVie&#44; Ferring&#44; MSD&#44; Falk&#44; Tillots Pharma&#44; Janssen&#44; Pfizer and Takeda&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Dr L&#46; Mata&#58; scientific advice&#44; support for research and&#47;or training activities for Janssen&#44; AbbVie&#44; Faes and Takeda&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Dr M&#46; V&#225;squez&#58; no conflict of interest&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Dr A&#46; Carbajo&#58; support for training activities for Jannsen and AbbVie&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Dr N&#46; Alcaide&#58; no conflict of interest&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">RN N&#46; Cano&#58; scientific advice&#44; support for research and&#47;or training activities for Janssen&#44; Sandoz&#44; Takeda&#44; AbbVie and MSD&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Dr A&#46; Nu&#241;ez&#58; support for training activities for Jannsen and AbbVie&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Dr P&#46; Fradejas&#58; scientific advice&#44; support for research and&#47;or training activities for AbbVie&#44; FAES&#44; Falk&#44; Ferring&#44; Kern Pharma&#44; MSD&#44; Pfizer Pharma and Takeda&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Dr M&#46; Ib&#225;&#241;ez&#58; scientific advice&#44; support for research and&#47;or training activities for Janssen&#44; AbbVie&#44; Faes and Takeda&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Dr L&#46; Hern&#225;ndez&#58; no conflicts of interest&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Dr B&#46; Sicilia&#58; scientific advice&#44; support for research and&#47;or training activities for Tillots Pharma&#44; Kern Pharma&#44; AbbVie&#44; Janssen&#44; Pfizer and Takeda&#46;</p></span></span>"
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            1 => "Inflammatory bowel disease"
            2 => "Crohn&#8217;s disease"
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            5 => "Treatment"
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            0 => "Incidencia"
            1 => "Enfermedad inflamatoria intestinal"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The incidence of Inflammatory Bowel Disease &#40;IBD&#41; is increasing worldwide&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">To evaluate the incidence of IBD in Castilla y Le&#243;n describing clinical characteristics of the patients at diagnosis&#44; the type of treatment received and their clinical course during the first year&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Prospective&#44; multicenter and population-based incidence cohort study&#46; Patients aged&#62;18 years diagnosed during 2017 with IBD &#40;Crohn&#8217;s disease &#91;CD&#93;&#44; ulcerative colitis &#91;UC&#93; and indeterminate colitis &#91;IC&#93;&#41; were included from 8 hospitals in Castilla y Le&#243;n&#46; Epidemiological&#44; clinical&#44; and therapeutic variables were registered&#46; The global incidence and disease incidence were calculated&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">290 patients were diagnosed with IBD &#40;54&#46;5&#37; UC&#44; 45&#46;2&#37; CD&#44; and 0&#46;3&#37; IC&#41;&#44; with a median follow-up of 9 months &#40;range 8-11&#41;&#46; The incidence rate of IBD in Castilla y Leon in 2017 was 16&#46;6 cases per 10&#46;000 inhabitants-year &#40;9&#47;10<span class="elsevierStyleSup">5</span> UC cases and 7&#46;5&#47;10<span class="elsevierStyleSup">5</span> CD cases&#41;&#44; with a UC&#47;CD ratio of 1&#46;2&#58;1&#46; Use of systemic corticosteroids &#40;47&#37; vs&#46; 30&#37; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; immunomodulatory therapy &#40;81&#37; vs&#46; 19&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#44; biological therapy &#40;29&#37; vs&#46; 8&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#44; and surgery &#40;11&#37; vs&#46; 2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41; were significatively higher among patients with CD comparing with those with UC&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">The incidence of patients with UC in our population increases while the incidence of patients with CD remains stable&#46; Patients with CD presents a worse natural history of the disease &#40;use of corticosteroids&#44; immunomodulatory therapy&#44; biological therapy and surgery&#41; compared to patients with UC in the first year of follow-up&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La incidencia de la enfermedad inflamatoria intestinal &#40;EII&#41; est&#225; aumentando en todo el mundo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Evaluar la incidencia de EII en la Comunidad Aut&#243;noma de Castilla y Le&#243;n y describir las caracter&#237;sticas cl&#237;nicas de los pacientes al diagn&#243;stico&#44; el tipo de tratamiento recibido y la evoluci&#243;n cl&#237;nica durante el primer a&#241;o&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y m&#233;todos</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo&#44; multic&#233;ntrico y poblacional en el que se incluyeron pacientes adultos diagnosticados de EII &#40;enfermedad de Crohn &#91;EC&#93;&#44; colitis ulcerosa &#91;CU&#93; o colitis indeterminada &#91;CI&#93; durante el a&#241;o 2017 procedentes de 8 centros de Castilla y Le&#243;n&#46; Se incluyeron variables epidemiol&#243;gicas&#44; cl&#237;nicas y terap&#233;uticas&#46; Se calcul&#243; la incidencia global y por enfermedades&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Doscientos noeventa pacientes fueron diagnosticados de EII &#40;54&#44;5&#37; de CU&#44; 45&#46;2&#37; de EC y 0&#44;3&#37; de CI&#41;&#44; con una mediana de seguimiento de 9 meses &#40;rango 8&#8211;11&#41;&#46; La tasa de incidencia fue de 16&#46;6 casos&#47;100&#46;000 habitantes-a&#241;o &#40;9&#47;10<span class="elsevierStyleSup">5</span> casos de CU y 7&#46;5&#47;10<span class="elsevierStyleSup">5</span> casos de EC&#41;&#44; con una proporci&#243;n CU&#47;EC de 1&#44;2&#58;1&#46; Los pacientes con EC recibieron significativamente m&#225;s corticoides sist&#233;micos &#40;47&#37; vs&#46; 30&#37; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; m&#225;s tratamiento inmunomodulador &#40;81&#37; vs&#46; 19&#37; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#44; m&#225;s tratamiento biol&#243;gico &#40;29&#37; vs&#46; 8&#37; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41; y mayor necesidad de cirug&#237;a &#40;11&#37; vs&#46; 2&#37; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">La incidencia de pacientes con CU en nuestro medio se incrementa mientras que la de EC se mantiene estable&#44; con una historia natural de la enfermedad peor &#40;uso de corticoides&#44; inmunosupresores&#44; biol&#243;gicos y cirug&#237;a&#41; para los pacientes con EC comparado con los pacientes con CU en el primer a&#241;o de seguimiento&#46;</p></span>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as median&#44; interquartile range &#40;IQR&#41;&#44; absolute and relative frequency&#46; Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test or Chi Square &#40;Fisher&#41; test&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">CD&#58; Crohn&#39;s disease&#59; IBD&#58; inflammatory bowel disease&#59; UC&#58; ulcerative colitis&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">In bold&#44; statistically significant differences between UC and CD&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">UC &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>158&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;37&#8722;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;233&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male gender&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84 &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;323&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean follow-up time&#44; months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;8&#8722;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;8&#8722;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;7&#46;5&#8722;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;768&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time to diagnosis&#44; months &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#8722;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;0&#46;7&#8722;10&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#8722;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Family history IBD&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;028&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Extraintestinal manifestations&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;188&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smoker&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;000</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mesalazine&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">160 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">141 &#40;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;000</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systemic corticosteroids&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;002</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rectal corticosteroids&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;0&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;026</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Topical oral corticosteroids&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;000</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunomodulators&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;000</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biologics&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;000</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospitalisation due to flare-up&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Surgery&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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