Journal of Clinical Medicine Article Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study María Chaparro 1, *,† , Ana Garre 1,† , Andrea Núñez Ortiz 2 , María Teresa Diz-Lois Palomares 3 , Cristina Rodríguez 4 , Sabino Riestra 5 , Milagros Vela 6 , José Manuel Benítez 7 , Estela Fernández Salgado 8 , Eugenia Sánchez Rodríguez 9 , Vicent Hernández 10 , Rocío Ferreiro-Iglesias 11 , Ángel Ponferrada Díaz 12 , Jesús Barrio 13 , José María Huguet 14 , Beatriz Sicilia 15 , María Dolores Martín-Arranz 16 , Xavier Calvet 17 , Daniel Ginard 18 , Inmaculada Alonso-Abreu 19 , Luis Fernández-Salazar 20 , Pilar Varela Trastoy 21 , Montserrat Rivero 22 , Isabel Vera-Mendoza 23 , Pablo Vega 24 , Pablo Navarro 25 , Mónica Sierra 26 , José Luis Cabriada 27 , Mariam Aguas 28 , Raquel Vicente 29 , Mercè Navarro-Llavat 30 , Ana Echarri 31 , Fernando Gomollón 32 , Elena Guerra del Río 33 , Concepción Piñero 34 , María José Casanova 1 , Katerina Spicakova 35 , Jone Ortiz de Zarate 36 , Emilio Torrella Cortés 37 , Ana Gutiérrez 38 , Horacio Alonso-Galán 39 , Álvaro Hernández-Martínez 40 , José Miguel Marrero 41 , Rufo Lorente Poyatos 42 , Margalida Calafat 43 , Lidia Martí Romero 44 , Pilar Robledo 45 , Orencio Bosch 46 , Nuria Jiménez 47 , María Esteve Comas 48 , José María Duque 49 , Ana María Fuentes Coronel 50 , Manuela Josefa Sampedro 51 , Eva Sesé Abizanda 52 , Belén Herreros Martínez 53 , Liliana Pozzati 54 , Hipólito Fernández Rosáenz 55 , Belén Crespo Suarez 56 , Pilar López Serrano 57 , Alfredo J. Lucendo 58,59,60 , Margarita Muñoz Vicente 61 , Fernando Bermejo 62 , José Joaquín Ramírez Palanca 63 , Margarita Menacho 64 , Amalia Carmona 65 , Raquel Camargo 66 , Sandra Torra Alsina 67 , Nuria Maroto 68 , Juan Nerín de la Puerta 69 , Elena Castro 70 , Ignacio Marín-Jiménez 71 , Belén Botella 72 , Amparo Sapiña 73 , Noelia Cruz 74 , José Luis F. Forcelledo 75 , Abdel Bouhmidi 76 , Carlos Castaño-Milla 77 , Verónica Opio 78 , Isabel Nicolás 79 , Marcos Kutz 80 , Alfredo Abraldes Bechiarelli 81 , Jordi Gordillo 82 , Yolanda Ber 83 , Yolanda Torres Domínguez 84 , María Teresa Novella Durán 85 , Silvia Rodríguez Mondéjar 86 , Francisco J. Martínez-Cerezo 87 , Lilyan Kolle 88 , Miriam Sabat 89 , Cesar Ledezma 90 , Eduardo Iyo 91 , Óscar Roncero 92 , Rebeca Irisarri 93 , Laia Lluis 94 , Isabel Blázquez Gómez 95 , Eva María Zapata 96 , María José Alcalá 97 , Cristina Martínez Pascual 98 , María Montealegre 99 , Laura Mata 100 , Ana Monrobel 101 , Alejandro Hernández Camba 102 , Luis Hernández 103 , María Tejada 104 , Alberto Mir 105 , María Luisa Galve 106 , Marta Soler 107 , Daniel Hervías 108 , José Antonio Gómez-Valero 109 , Manuel Barreiro-de Acosta 11 , Fernando Rodríguez-Artalejo 110 , Esther García-Esquinas 110 , Javier P. Gisbert 1 and on behalf of the EpidemIBD study group of GETECCU ‡  1 Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria  Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Citation: Chaparro, M.; Garre, A.; Enfermedades Hepáticas y Digestivas (CIBERehd), 28006 Madrid, Spain; Núñez Ortiz, A.; Diz-Lois Palomares, anagarre.laprincesa@gmail.com (A.G.); mjcasanova.g@gmail.com (M.J.C.); javier.p.gisbert@gmail.com (J.P.G.) M.T.; Rodríguez, C.; Riestra, S.; Vela, 2 Department of Gastroenterology, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain; M.; Benítez, J.M.; Fernández Salgado, E.; Sánchez Rodríguez, E.; et al. andreanuor@gmail.com 3 Department of Gastroenterology, Hospital Universitario A Coruña, 15006 A Coruña, Spain; Incidence, Clinical Characteristics and Management of Inflammatory maitedlp@yahoo.es Bowel Disease in Spain: Large-Scale 4 Department of Gastroenterology, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain; Epidemiological Study. J. Clin. Med. cristina.rodriguez.gutierrez@cfnavarra.es 2021, 10, 2885. https://doi.org/ 5 Department of Gastroenterology, Hospital Universitario Central de Asturias and ISPA, 33011 Oviedo, Spain; 10.3390/jcm10132885 sriestram7@gmail.com 6 Department of Gastroenterology, Complejo Hospitalario Universitario Ntra. Sra. de Candelaria, Academic Editor: Angelo Viscido 38010 Santa Cruz de Tenerife, Spain; Milvelillas@yahoo.es 7 Department of Gastroenterology, Hospital Universitario Reina Sofía and IMIBIC, 14004 Córdoba, Spain; Received: 19 May 2021 Accepted: 15 June 2021 jmbeni83@hotmail.com 8 Department of Gastroenterology, Complexo Hospitalario Universitario de Pontevedra, Instituto de Published: 29 June 2021 Investigación Sanitaria Galicia Sur, 36071 Pontevedra, Spain; estela.fernandez.salgado@sergas.es 9 Department of Gastroenterology, Hospital Ramón y Cajal, 28034 Madrid, Spain; Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in eugenia.sanchez.rodriguez@gmail.com 10 Department of Gastroenterology, Hospital Álvaro Cunqueiro, Estrutura Organizativa de Xestión Integrada published maps and institutional affil- de Vigo, 36213 Vigo, Spain; vicent.Hernandez.Ramirez@sergas.es iations. J. Clin. Med. 2021, 10, 2885. https://doi.org/10.3390/jcm10132885 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 2885 2 of 19 11 Department of Gastroenterology, Complexo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain; rocioferstg@hotmail.com (R.F.-I.); Copyright: © 2021 by the authors. manubarreiro@hotmail.com (M.B.-d.A.) 12 Department of Gastroenterology, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain; Licensee MDPI, Basel, Switzerland. This article is an open access article angelponmedicina@yahoo.es 13 Department of Gastroenterology, Hospital Universitario Rio Hortega, 47012 Valladolid, Spain; distributed under the terms and jbarrioa95@gmail.com conditions of the Creative Commons 14 Department of Gastroenterology, Consorcio Hospital General Universitario de Valencia, 46014 Valencia, Attribution (CC BY) license (https:// Spain; josemahuguet@gmail.com creativecommons.org/licenses/by/ 15 Department of Gastroenterology, Hospital Universitario de Burgos, 09006 Burgos, Spain; bsicilia4@gmail.com 4.0/). 16 Department of Gastroenterology, Hospital Universitario La Paz, 28046 Madrid, Spain; mmartinarranz@gmail.com 17 Servei de Malalties Digestives, Hospital de Sabadell, Institut Universitari Parc Taulí, Universitat Autònoma de Barcelona, CIBEREHD—Instituto de Salud Carlos III, Parc Taulí, 1, 08208 Sabadell, Barcelona, Spain; xcalvet@tauli.cat 18 Department of Gastroenterology, Hospital Universitari Son Espases, 07120 Palma de Mallorca, Spain; daniel.ginard@gmail.com 19 Department of Gastroenterology, Hospital Universitario de Canarias (H.U.C.), 38320 Santa Cruz de Tenerife, Spain; inmaculadaalonsoabreu@gmail.com 20 Department of Gastroenterology, Hospital Clínico Universitario de Valladolid, 47003 Valladolid, Spain; luisfernsal@gmail.com 21 Department of Gastroenterology, Hospital de Cabueñes, 33394 Gijón, Spain; trastoy@hotmail.com 22 Department of Gastroenterology, Hospital Universitario Marqués de Valdecilla and IDIVAL, 39008 Santander, Spain; digrtm@humv.es 23 Department of Gastroenterology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain; isabel.veramendoza@gmail.com 24 Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, 32005 Ourense, Spain; PABLO.VEGA.VILLAAMIL@sergas.es 25 Department of Gastroenterology, Hospital Clínico Universitario de Valencia, Universitat de València, 46010 Valencia, Spain; pnavarrocortes@gmail.com 26 Department of Gastroenterology, Complejo Asistencial Universitario de León, 24001 León, Spain; msierra.ausin@gmail.com 27 Department of Gastroenterology, Hospital de Galdakao-Usansolo, Galdakao, 48960 Vizcaya, Spain; joseluis.cabriadanuno@osakidetza.eus 28 Department of Gastroenterology, Hospital Universitari i Politecnic La Fe and CIBERehd, 46026 Valencia, Spain; aguas_mar@gva.es 29 Department of Gastroenterology, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; raquelvicentelidon@gmail.com 30 Department of Gastroenterology, Hospital de Sant Joan Despí Moisès Broggi, 08970 Barcelona, Spain; mnavarrollavat@gmail.com 31 Department of Gastroenterology, Complejo Hospitalario Universitario de Ferrol, 15405 A Coruña, Spain; ana.echarri.piudo@sergas.es 32 Department of Gastroenterology, Hospital Clínico Universitario “Lozano Blesa”, IIS Aragón and CIBERehd, 50009 Zaragoza, Spain; fgomollon@gmail.com 33 Department of Gastroenterology, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas, Spain; elenoti@hotmail.com 34 Department of Gastroenterology, Hospital Universitario de Salamanca, 37007 Salamanca, Spain; conxipi@hotmail.com 35 Department of Gastroenterology, Hospital Universitario de Araba (sede Txagorritxu y sede Santiago), 01009 Álava, Spain; katerina.spicakova-@osakidetza.eus 36 Department of Gastroenterology, Hospital Universitario de Basurto, 48013 Bilbao, Spain; jone.ortizdezaratesagastagoitia@osakidetza.net 37 Department of Gastroenterology, Hospital General Universitario J.M. Morales Meseguer, 30008 Murcia, Spain; emilioa.torrella@gmail.com 38 Department of Gastroenterology, Hospital General Universitario de Alicante and CIBERehd, 03010 Alicante, Spain; gutierrez_anacas@gva.es 39 Department of Gastroenterology, Hospital Universitario Donostia-Donostia Unibertsitate Ospitalea, Guipuzkoa and Organizacion Sanitaria Integrada Tolosaldea, Clínica Santa María de la Asunción, 20014 Guipúzcoa, Spain; horacio.alonsogalan@osakidetza.eus 40 Department of Gastroenterology, Complejo Hospitalario de Especialidades Torrecárdenas, 04009 Almería, Spain; alvarohernandezm68@gmail.com 41 Department of Gastroenterology, Hospital Universitario Insular de Gran Canaria, 35016 Las Palmas, Spain; marreromonroy@hotmail.com J. Clin. Med. 2021, 10, 2885 3 of 19 42 Department of Gastroenterology, Hospital General Universitario de Ciudad Real, 13005 Ciudad Real, Spain; rufolorente@hotmail.com 43 Department of Gastroenterology, Hospital Son Llatzer, 07198 Palma de Mallorca, Spain; margalidasard.calafat@gmail.com 44 Department of Gastroenterology, Hospital Francesc De Borja de Gandía, 46702 Valencia, Spain; lidia.marti.romero@gmail.com 45 Department of Gastroenterology, Hospital Universitario de Cáceres, 10004 Cáceres, Spain; probledoa@gmail.com 46 Department of Gastroenterology, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain; OBosch@quironsalud.es 47 Department of Gastroenterology, Hospital General Universitario de Elche, 03203 Alicante, Spain; nurjime@gmail.com 48 Department of Gastroenterology, Hospital Universitari Mutua Terrasa, 08221 Terrassa, Spain; mestevecomas@telefonica.net 49 Department of Gastroenterology, Hospital San Agustín, 33401 Avilés, Spain; josemaria.duque@sespa.es 50 Department of Gastroenterology, Hospital Virgen de La Concha, Complejo Asistencial de Zamora, 49022 Zamora, Spain; amfcoronel@gmail.com 51 Department of Gastroenterology, CSDM, Hospital de Mataró, 08304 Barcelona, Spain; msampedro@csdm.cat 52 Department of Gastroenterology, Hospital Universitario Arnau de Vilanova, 25198 Lérida, Spain; eseseabi@gmail.com 53 Department of Gastroenterology, Hospital De Villajoyosa, 03570 Alicante, Spain; belherreros@gmail.com 54 Department of Gastroenterology, Hospital de Mérida, 06800 Mérida, Spain; santelmo0054@hotmail.com 55 Department of Gastroenterology, Hospital San Pedro, 26006 Logroño, Spain; hfrosaenz@riojasalud.es 56 Department of Gastroenterology, Hospital da Costa (EOXI Lugo-Cervo-Monforte), 27880 Lugo, Spain; belen.Crespo.Suarez@sergas.es 57 Department of Gastroenterology, Hospital Universitario Fundación Alcorcón, 28922 Madrid, Spain; plopez@fhalcorcon.es 58 Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; ajlucendo@hotmail.com 59 Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain 60 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28006 Madrid, Spain 61 Department of Gastroenterology, Hospital General Universitario de Castellón, 12004 Castellón, Spain; munyoz_marvice@yahoo.es 62 Department of Gastroenterology, Hospital Universitario de Fuenlabrada and Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), 28942 Madrid, Spain; fbermejos1@gmail.com 63 Department of Gastroenterology, Hospital Lluis Alcanyis, Xátiva, 46800 Valencia, Spain; joramirezpa@gmail.com 64 Department of Gastroenterology, Hospital Joan XXIII, 43005 Tarragona, Spain; mmenacho.hj23.ics@gencat.cat 65 Department of Gastroenterology, Hospital Povisa, 36211 Pontevedra, Spain; amiccar@hotmail.com 66 Department of Gastroenterology, Complejo Hospitalario de Especialidades Virgen de la Victoria, 29010 Málaga, Spain; raquelcamero@hotmail.com 67 Department of Gastroenterology, Parc Sanitari Sant Joan de Déu, 08830 Barcelona, Spain; sandra.torra@pssjd.org 68 Department of Gastroenterology, Hospital de Manises, 46940 Valencia, Spain; nmaroto@hospitalmanises.es 69 Department of Gastroenterology, Hospital Royo Villanova, 50015 Zaragoza, Spain; jmnerindlp@gmail.com 70 Department of Gastroenterology, Complexo Hospitalario Universitario Xeral-Calde de Lugo, 27004 Lugo, Spain; elecortiz@yahoo.es 71 Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón (IiSGM), 28007 Madrid, Spain; drnachomarin@hotmail.com 72 Department of Gastroenterology, Hospital Universitario Infanta Cristina, 28981 Madrid, Spain; belen.botella@salud.madrid.org 73 Department of Gastroenterology, Hospital de Manacor, 07500 Manacor, Spain; asapina@hospitalmanacor.org 74 Department of Gastroenterology, Hospital Doctor José Molina Orosa, 35500 Lanzarote, Spain; noelia_ingenio@hotmail.com 75 Department of Gastroenterology, Hospital Comarcal Sierrallana, 39300 Torrelavega, Spain; jlforce2@yahoo.es 76 Department of Gastroenterology, Hospital Santa Bárbara, 13500 Puertollano, Spain; bumidi@hotmail.com 77 Department of Gastroenterology, Hospital Rey Juan Carlos, 28933 Madrid, Spain; castamilla@gmail.com 78 Department of Gastroenterology, Hospital Universitario de Getafe, 28905 Madrid, Spain; veronica.opio@salud.madrid.org 79 Department of Gastroenterology, Hospital General Universitario Reina Sofía, 30003 Murcia, Spain; isabelndp@hotmail.com 80 Department of Gastroenterology, Hospital Reina Sofía, 31500 Tudela, Spain; marcos.kutz.leoz@navarra.es J. Clin. Med. 2021, 10, 2885 4 of 19 81 Department of Gastroenterology, Hospital Puerta del Mar, 11009 Cádiz, Spain; aljabbe@gmail.com 82 Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; jgordillo@santpau.cat 83 Department of Gastroenterology, Hospital San Jorge, 22004 Huesca, Spain; ybernieto@gmail.com 84 Department of Gastroenterology, Hospital San Juan de Dios del Aljarafe, 41930 Sevilla, Spain; ytgastrosur@gmail.com 85 Department of Gastroenterology, Hospital Can Misses, 07800 Ibiza, Spain; mnovella@asef.es 86 Department of Gastroenterology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain; silvia36455@live.com 87 Department of Gastroenterology, Hospital Universitari Sant Joan, 25001 Lérida, Spain; fjmartinez@grupsagessa.com 88 Department of Gastroenterology, Hospital General de La Palma, 38713 Santa Cruz de Tenerife, Spain; lkolle@hotmail.com 89 Department of Gastroenterology, Hospital Santa Caterina, 17190 Gerona, Spain; miriam.sabat@ias.cat 90 Department of Gastroenterology, Hospital Palamós, 17230 Girona, Spain; Cesar_kike@hotmail.com 91 Department of Gastroenterology, Hospital Comarcal de Inca, 07300 Inca, Spain; eduardoy.iyo@hcin.es 92 Department of Gastroenterology, Hospital General La Mancha Centro, 13600 Ciudad Real, Spain; dr.roncero@gmail.com 93 Department of Gastroenterology, Hospital García Orcoyen, 31200 Estella, Spain; rebeca.irisarri.garde@navarra.es 94 Department of Gastroenterology, Hospital Sagrat Cor, 08029 Barcelona, Spain; laia.lluis@quironsalud.es 95 Department of Gastroenterology, Hospital de Torrejón, 28850 Madrid, Spain; isa.blazquezgomez@gmail.com 96 Department of Gastroenterology, Hospital de Mendaro, 20850 Guipuzkoa, Spain; evazapatamorcillo@gmail.com 97 Department of Gastroenterology, Hospital Obispo Polanco, 44002 Teruel, Spain; mjaescriche@gmail.com 98 Department of Gastroenterology, Hospital General Universitario Los Arcos del Mar Menor, San Javier, 30739 Murcia, Spain; cristina.martinezpascual@gmail.com 99 Department of Gastroenterology, Hospital General de Villarobledo, 02600 Albacete, Spain; montealegre_m@hotmail.com 100 Department of Gastroenterology, Hospital Medina del Campo, 47400 Valladolid, Spain; lauramataroman@gmail.com 101 Department of Gastroenterology, Hospital de Montilla, 14550 Córdoba, Spain; ammonrobel@ephag.es 102 Department of Gastroenterology, Hospital Quirón Costa Adeje, 38660 Santa Cruz de Tenerife, Spain; Dr.alejandrohc@gmail.com 103 Department of Gastroenterology, Hospital Santos Reyes, 09400 Aranda de Duero, Spain; luishernandezvillalba@gmail.com 104 Department of Gastroenterology, Clínica Astarté, 11011 Cádiz, Spain; maria.tejada.cabrera@gmail.com 105 Department of Gastroenterology, Hospital Ernest Lluch, 50299 Zaragoza, Spain; albertomirsubias@gmail.com 106 Department of Gastroenterology, Hospital Central de La Cruz Roja San José y Santa Adela, 28003 Madrid, Spain; marisagalve@gmail.com 107 Department of Gastroenterology, Hospital San Juan De Dios, 38009 Tenerife, Spain; msolerrguez@yahoo.es 108 Department of Gastroenterology, Hospital Virgen de Altagracia, 13002 Manzanares, Spain; danielhervias@gmail.com 109 Department of Gastroenterology, Hospital Dexeus, 08028 Barcelona, Spain; jagomez@idexeus.es 110 Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPaz and CIBERESP, 28029 Madrid, Spain; fernando.artalejo@uam.es (F.R.-A.); esthergge@gmail.com (E.G.-E.) * Correspondence: mariachs2005@gmail.com; Tel.: +34-913093911 † Both authors share first authorship. ‡ Membership of the EpidemIBD study group of GETECCU is provided in the Acknowledgments. Abstract: (1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. J. Clin. Med. 2021, 10, 2885 5 of 19 Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. Keywords: epidemiology; incidence; inflammatory bowel disease; Crohn’s disease; ulcerative colitis 1. Introduction Inflammatory bowel diseases (IBD)—Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U)—are chronic inflammatory conditions that mainly affect the gastrointestinal tract but might also involve other organs, so they are considered systemic diseases. IBD is mainly diagnosed in young people, and is associated with significant morbidity and disability [1]. In the last decades, the global burden of IBD has increased due to its growth in newly industrialized countries, increased rates of diagnosis and decline in mortality [1]. In a recent systematic review, authors found that the prevalence of IBD today exceeds 0.3% of the total population in countries like Canada, the United States, New Zealand, Denmark, Germany and the United Kingdom [2]. Furthermore, a predictive model for Canada revealed that the prevalence of IBD in 2025 could rise to 0.9% [3]. The growing disease burden is aggravated by increasing costs in the last years. In recent years, the therapeutic target in IBD management has moved from control of symptoms to mucosal healing [4] and more effective therapeutic, but also costly, options have been introduced [5,6]. For this reason, new epidemiological evidence is needed to better understand the penetration of new therapeutic algorithms. Nationwide epidemiological studies are necessary to ensure representativeness and limit the impact of regional variability on the results. However, there is a paucity of nationwide epidemiological studies on IBD; in Europe, most of them have been carried out in countries with relatively small populations in Northern or Central Europe [7–9], and have seldom included data on Southern Europe countries. In addition, most nationwide studies are based on administrative data being at risk of exposure to misclassification or confounding bias [10]. In Europe, the EpiCom/Epi-IBD study was initiated in 2010 to investigate the dif- ferences in epidemiology and management of IBD between Eastern and Western coun- tries. A total of 1515 IBD patients were included over 2010, reporting an incidence of 15 cases/100,000 person-years [11]. In Spain, only one center was involved in the EpiCom study, and previous epidemiological studies were performed many years ago, in selected areas, and included a small number of patients [12]. The aims of the present study were to assess the incidence of IBD in Spain, describe the characteristics of patients at diagnosis and their use of immunosuppressive treatments and biological drugs, and measure the cumulative incidence of surgeries and hospital admissions during the first year after IBD diagnosis. 2. Methods 2.1. Study Design EpidemIBD is a prospective, population-based incidence cohort of adult patients aiming to assess the incidence and clinical characteristics of IBD (CD, UC, or IBD-U), in Spain. In addition, each incident case is being followed to determine changes in disease phenotype or location, the exposure to immunosuppressive and biologic treatments, and the need for hospital admission or surgery during the first 5 years after diagnosis. In the present study, we describe baseline characteristics of study participants, and provide data J. Clin. Med. 2021, 10, 2885 6 of 19 on the cumulative incidence of treatment use, hospitalizations and surgeries during the first 12 months after diagnosis. The study protocol, which has already been published [12], was approved by the Research Ethics Committee of the coordinating hospital (Hospital Universitario de La Princesa, Madrid). All patients provided written informed consent to participate. 2.2. Study Population As previously described in the protocol, adult (≥18 years of age) IBD patients di- agnosed between 1 January 2017 and 31 December 2017 in the study centers were in- cluded [12]. Diagnosis of IBD was based on European Crohn’s and Colitis Organisation criteria [13,14]. Patients were eligible to be included in the IBD incident cohort if they belonged to the reference area of the participating centers. A patient diagnosed at one center (e.g., a particular hospital in Madrid) who was part of the reference population of another center (e.g., a different hospital in Madrid) was assigned to his/her own reference population (in this example, that of his/her usual hospital). 2.3. Recruitment and Patient Follow-Up This study is being conducted at 108 centers, 100 of them within the National Health System (providing free access to healthcare). The initial selection of centers was made from the database of health centers of the Ministry of Health, which included 893 centers in 2016. A total of 205 centers were selected to start the study. Centers that did not adequately follow the study procedures or ensure the inclusion of all patients diagnosed with IBD in their area were excluded [12]. Finally, 108 centers continue to be involved in the study, covering a referral area with a population of 22,270,357 inhabitants (approximately 50% of Spanish population, which was 46,659,302 as of 28 June 2018) [15]. Once an incident patient was included in the registry, two additional visits, at 3 and 12 months, were performed during the first year to confirm the diagnosis and to update the information regarding disease extent and behavior, medical treatments, hospitalizations and surgeries. Patients are being followed-up every 6 months until completing 5 years from IBD diagnosis. Misdiagnosed patients were excluded from the analysis. Remote monitoring was performed by the research staff to ensure data quality. 2.4. Definitions IBD location and phenotype were defined according to the Montreal classification [16]. Time to diagnosis was defined as the time from the first medical consultation by a symp- tomatic patient to the diagnosis of IBD. Socioeconomic level was assessed considering the patient’s educational level (pri- mary or lower, secondary, higher education), occupational (self-employed, employed, unemployed, retired) and professional status (non-salaried or salaried). The number of co- habitants at the patient’s home during his/her childhood (up to 16 years) and at diagnosis of IBD was also recorded. Smoking status was categorized at the time of diagnosis of IBD as “nonsmoker”, “former smoker”, or “smoker”. Patients were considered “smokers” if they smoked more than 7 cigarettes per week for at least 6 months and had smoked at least 1 cigarette in the 6 months prior to diagnosis. Patients were considered “ex-smokers” if they quit smoking at least 6 months before diagnosis. Patients were considered “nonsmokers” if they never smoked or did so in very small amounts or occasionally [17]. Hospitals were clustered in conglomerates taking into account different variables provided in the database from the Spanish Ministry of Health, such as provision, offer of services, activity, complexity or teaching, which established the following five categories: (1) Small general hospitals (less than 150 beds on average, hardly any high-tech resources, low complexity); (2) Medium general hospitals (average size less than 200 beds, minimal technological resources, some teaching activity and more complexity); (3) General hospi- tals (of average size around 500 beds, medium complexity); (4) Referral hospitals (large J. Clin. Med. 2021, 10, 2885 7 of 19 hospitals but heterogeneous in resources, size and activity, great teaching activity and high complexity); and (5) Large referral hospitals (great structural weight and a lot of activity, full offer of services, more than 600 doctors and around 300 residents). To analyze the impact of the hospital category on patients’ care, patients were considered belonging to the center that included them in the registry, in case it was different from the patients’ referral center. 2.5. Data Collection and Follow-Up Study data were collected and managed using an electronic data capture tool (Re- search Electronic Data Capture [REDCap]) [18], which is hosted at Asociación Española de Gastroenterología (AEG; www.aegastro.es, accessed date 15 May 2021), a non-profit medical society. AEG provided this service free of charge, with the aim of promoting investigator-driven research. 2.6. Statistical Analysis The reference population (based on estimates form the National Statistics Office) for the analyses is the population of the catchment areas of the participating centers [15]. The incidence rate (number of incident cases per 100,000 inhabitants) during one year was calculated using the reference population as denominator. Mean and standard deviation or median and interquartile range (IQR) were calculated for quantitative variables, depending on whether they were normally distributed or not. Categorical variables were compared using Chi-square (χ2 ) test and quantitative variables using the appropriate test. Qualitative variables were compared using the chi-square (χ2 ) test and the Fisher’s exact test. The Kaplan–Meier method was used to estimate the time course of treatment use, hospital admissions and surgery; the differences between the curves were assessed with the log-rank test. Use of different therapeutic choices was compared based on the type of IBD and hospital characteristics (see above). The main aim of this study was to cal- culate the incidence of IBD in Spain and to describe the characteristics and the use of treatments, surgeries and hospitalisations in this population; therefore, no multivariate analysis was performed. 3. Results 3.1. Incidence of IBD A total of 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million adult inhabitants (about 50% of the Spanish population) comprise the study cohort (Table 1). The overall cumulative incidence (cases/100,000 person-years) during the first year of follow-up was 16.2 for IBD, 7.4 for CD, 8.1 for UC, and 0.7 for IBD-U (Figure 1). Incidence of CD was somewhat higher in Central Spain, while that of UC was higher in Northern Spain (Asturias and Navarra) (Figure 1 and Supplementary Table S1). Table 1. Characteristics of the inception cohort. Overall n = 3611 Age, years (median, IQR) 42 (30–55) Male gender, n (%) 1908 (53) Former smokers, n (%) 880 (24.5) Symptoms at diagnosis, n (%) 3280 (92) Diagnostic delay, months (median, IQR) 3 (1–9) Family history of IBD, n (%) 524 (15) Educational level Primary or none 1220 (31) Secondary 1424 (41) University degree 961 (28) J. Clin. Med. 2021, 10, 2885 8 of 19 Table 1. Cont. Overall n = 3611 Employment status Self-employed 351 (10) Employee 1755 (51) Unemployed 532 (15.4) Others 326 (9.5) Extraintestinal manifestations, n (%) 327 (9) Crohn’s disease, n (%) 1647 (46) Ileal, n (%) 900 (55) Colonic, n (%) 312 (19) Ileocolonic, n (%) 431 (26) Upper gastrointestinal tract, n (%) 52 (3) Inflammatory, n (%) 1347 (82) Stricturing, n (%) 183 (11) Fistulizing, n (%) 114 (7) Perianal, n (%) 185 (11) Ulcerative colitis, n (%) 1807 (50) Extensive, n (%) 563 (31) Left-sided colitis, n (%) 563 (31) Proctitis, n (%) 678 (38) Unclassified inflammatory bowel disease, n (%) 156 (4) Interquartile range, IQR; inflammatory bowel disease, IBD. 3.2. Patients’ Characteristics Table 1 shows the main baseline characteristics of participants. Approximately 50% of them were male, with a median age of 42 years. A total of 1807 (50%) patients had UC, 1647 (46%) had CD, and 156 (4%) IBD-U. Around 8% of patients were asymptomatic at diagnosis. Median diagnosis delay (from symptom onset to IBD diagnosis) was 3 months (IQR = 1–9 months). Median time from primary care consultation to IBD diagnosis was 2 months (IQR = 1–6 months), and from gastroenterologist consultation to IBD diagnosis 0 months (IQR = 0–1 month). Family history of IBD was present in 525 patients (15%): 441 (12%) had one and 84 (2.5%) more than one relative with IBD. In total, 175 (4.8%) patients had first-degree relatives with IBD. In 176 (4.9%) patients, the closest relatives with IBD were second-degree relatives, and in 173 (4.8%) third-degree relatives. A total of 327 (9%) patients had extraintestinal manifestations at diagnosis. The most frequent was peripheral arthropathy (4%), followed by skin manifestations (1.8%), and spondiloarthropathy (1.3%) (Supplementary Table S2). In patients with CD, the majority of patients had ileal (55%) or ileocolonic (26%) involvement (Table 1). Inflammatory behavior was the most prevalent in our cohort (82%); however, 11% had stricturing and 7% fistulizing behavior already at IBD diagnosis. With respect to UC patients, 31% had extensive colitis and 31% left-sided colitis. Examinations performed to diagnose IBD are shown in Supplementary Table S3. Almost all patients (99%) underwent colonoscopy, 17% CT-scan, 15% magnetic resonance enterography, 7.3% upper gastrointestinal endoscopy and 4.5% abdominal ultrasound. The diagnosis delay was longer for CD than for UC (5 vs. 2 months, p < 0.01; Table 2). The proportion of patients with symptoms at diagnosis was higher in UC than in CD (94 vs. 89%, p < 0.01). By contrast, those with CD had higher frequency of family history of the disease that those with UC (18 vs. 13%, p < 0.01), former smokers (38 vs. 12%, p < 0.01) and extraintestinal manifestations (12 vs. 6%, p < 0.01). J. Clin. Med. 2021, 10, 2885 9 of 19 Figure 1. Incidence of inflammatory bowel disease (A), Crohn’s disease (B) and ulcerative colitis (C) by Autonomous Communities in Spain in 2017 (cases/100,000 person-years). J. Clin. Med. 2021, 10, 2885 10 of 19 Table 2. Characteristics of the inception cohort based on inflammatory bowel disease type (Crohn’s disease vs. ulcerative colitis). Crohn’s Disease Ulcerative Colitis p n = 1647 n = 1807 Age, years (median, IQR) 41 (28–54) 46 (34–57) <0.05 Female gender, n (%) 821 (50) 808 (45) <0.05 Former smokers, n (%) 630 (38) 217 (12) <0.05 Symptoms at diagnosis, n (%) 1465 (89.5) 1675 (94) <0.05 Diagnostic delay, months (median, IQR) 5 (1–15) 2 (1–5) <0.05 Family history of IBD, n (%) 288 (18) 225 (13) <0.05 Extraintestinal manifestations, n (%) 204 (12) 114 (6) <0.05 Interquartile range, IQR; inflammatory bowel disease, IBD. 3.3. Drug Treatment and Surgery during the First 12 Months after Diagnosis About 35% of patients had received systemic steroids, 26% immunomodulators and 15% biological drugs (Table 3). When comparing CD and UC, while the cumulative incidence of exposure to mesalamine was significantly higher in UC and IBD-U, the use of steroids, immunomodulators and biologics was significantly higher in CD (Figure 2). Table 3. Use of inflammatory bowel disease drugs, surgery and hospitalizations in the entire cohort (A) and based on inflammatory bowel disease type (B) in the first year after diagnosis. (A) Total Number of Patients n = 3611 Mesalamine, n (%) 2450 (68) Steroids, n (%) 1916 (53) Systemic steroid therapy, n (%) 1252 (35) Immunomodulators, n (%) 936 (26) Thiopurines, n (%) 860 (24) Methotrexate, n (%) 114 (3.2) Cyclosporine, n (%) 13 (0.4) Tofacitinib, n (%) 2 (0.1) Biologics, n (%) 558 (15.5) Anti-TNF, n (%) 535 (14.8) Ustekinumab, n (%) 24 (0.7) Vedolizumab, n (%) 34 (0.9) Surgery, n (%) 199 (5.5) Hospital admissions, n (%) 1012 (28) (B) Crohn’s Disease Ulcerative Colitis p n = 1647 n = 1807 Mesalamine ever, n (%) 625 (38) 1681 (73) <0.01 Steroids ever, n (%) 1170 (71) 688 (38) <0.01 Systemic steroid therapy, n (%) 717 (43.5) 497 (27.5) <0.01 Immunomodulators, n (%) 746 (45) 174 (10) <0.01 Biologics, n (%) 415 (25) 132 (7) <0.01 Surgery, n (%) 174 (11) 23 (1.3) <0.01 Hospital admissions, n (%) 585 (35.5) 391 (22) <0.01 A total of 199 (5%) patients underwent surgery; 170 patients (4.7%) were operated once, 20 (0.6%) twice, 7 (0.2%) three times, and 2 (0.1%) four times within the first 12 months. The cumulative incidence of surgery was higher in CD than UC (11 vs. 1.3%, p < 0.01) (Figure 2). J. Clin. Med. 2021, 10, 2885 11 of 19 Figure 2. Cumulative incidence of exposure to treatments in Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U) during follow-up. 100 100 Cumulative incidence of exposure to systemic steroids Cumulative incidence of exposure to mesalamine 75 75 50 50 25 25 0 0 Time (months) Time (months) CD (%) 33 36 37 40 CD (%) 40 42 43 45 UC (%) 78 79 81 95 UC (%) 24 27 28 29 U-IBD (%) 82 86 87 95 U-IBD (%) 20 22 23 26 Cumulative incidence of exposure to immunomodulators 100 100 Cumulative incidence of exposure to bologics 75 75 50 50 25 25 0 0 Time (months) Time (months) CD (%) 31 41 46 50 CD (%) 13 18 24 29 UC (%) 5 7 10 11 UC (%) 4 5 7 9 IBD-U (%) 5 7 10 12 IBD-U (%) 1 4 6 8 100 Cumulative incidence of surgery 75 50 25 0 Time (months) CD (%) 7 9 10 12 UC (%) 1 1 2 2 IBD-U (%) 1 1 1 1 Figure 2. Cumulative incidence of exposure to mesalamine (1), systemic steroids (2), immunomodula- tors (3), biologics (4) and surgery (5) in Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U) during 1-year follow-up. 3.4. Hospitalizations A total of 1012 (28%) patients were hospitalized within the first 12 months: 585 (35%) in CD and 391 (21%) in UC. The main reasons for hospital admission are summarized in Supplementary Table S4. Eight-hundred fifteen (23%) patients were hospitalized once, 151 (4.2%) twice, 33 (0.9%) three times and 13 (0.5%) four times. 3.5. Drug Treatments, Surgery and Hospitalizations during the First 12 Months Based on Hospital Category Of the 108 participating hospitals, 100 were publicly funded by the National Health System and 8 of them were privately funded. Two (2%) hospitals were classified into category 1 (lowest resources), 4 (4%) into category 2, 44 (40%) into category 3, 31 (29%) into category 4, and 27 (25%) into category 5 (highest resources). J. Clin. Med. 2021, 10, 2885 12 of 19 In total, 177 patients were treated in hospitals with low resources (categories 1–2) and 3434 patients in hospitals with high resources (categories 3–5). The main characteristics of IBD patients were similar in both types of hospitals (Table 4). With respect to CD management, use of some drug treatments was different between hospitals with low and high resources (Table 5). Thus, the cumulative incidence of exposure to mesalamine in CD was higher in hospitals with low resources, while the cumulative incidence of exposure to systemic steroids was higher in hospitals with high resources (mainly due to higher proportion of patients starting systemic steroids at IBD diagnosis). In addition, use of biological drugs was also higher in CD patients from hospitals with high resources (Figure 3). The cumulative incidence of surgery and hospitalizations was similar in both groups. Regarding UC, the cumulative incidence of treatment with mesalamine, steroids, immunomodulators, biologics and surgery was similar in hospitals with low and high resources (Figure 4). Table 4. Patients’ characteristics based on hospital categories. Low Resources High Resources (Categories 1–2) (Categories 3–5) p n = 177 n = 3434 Age, years (median, IQR) 45 (31–55) 43 (31–56) >0.05 Male gender, n (%) 101 (57) 1807 (53) >0.05 Never smokers, n (%) 56 (32) 1410 (41) 0.01 Symptoms at diagnosis, n (%) 166 (94.3) 3114 (92) >0.05 Diagnostic delay, months (median, IQR) 4 (1–15) 3 (1–8) >0.05 Time from symptoms onset to primary 2 (0–6) 2 (1–6) >0.05 care consultation, months (median, IQR) Time from primary care to gastroenterologist consultation, months 1.5 (0–3) 2 (0–5) >0.05 (median, IQR) Family history of IBD, n (%) 24 (14) 501 (15) >0.05 Extraintestinal manifestations, n (%) 23 (13) 304 (9) >0.05 Crohn’s disease, n (%) 88 (50) 1559 (45.5) >0.05 Ileal, n (%) 57 (65) 843 (54) >0.05 Colonic, n (%) 10 (11) 302 (19.5) >0.05 Ileocolonic, n (%) 21 (24) 410 (26) >0.05 Upper gastrointestinal tract, n (%) 1 (1) 51 (3) >0.05 Inflammatory, n (%) 76 (86) 1271 (82) Stricturing, n (%) 9 (10) 174 (11) >0.05 Fistulizing, n (%) 3 (4) 111 (7) Perianal, n (%) 4 (4.5) 181 (11.7) 0.04 Ulcerative colitis, n (%) 82 (46) 1725 (50) >0.05 Extensive, n (%) 25 (31) 538 (31) Left-sided colitis, n (%) 24 (29) 539 (31) >0.05 Proctitis, n (%) 33 (40) 645 (38) Unclassified inflammatory bowel disease, 7 (4) 149 (4.5) >0.05 n (%) Interquartile range, IQR; inflammatory bowel disease, IBD. J. Clin. Med. 2021, 10, 2885 13 of 19 Figure 2. Cumulative incidence of exposure to treatments in Crohn’s disease (CD) based on hospital categories: low resources (1 and 2) vs. high resources (3-5). 100 100 Cumulative incidence of exposure to systemic steroids Cumulative incidence of exposure to mesalamine p<0.01 p<0.01 75 75 50 50 25 25 0 0 Time (months) Time (months) 1-2 (%) 43 52 52 55 1-2 (%) 27 28 30 32 3-5 (%) 32 35 36 38 3-5 (%) 40 43 44 45 Cumulative incidence of exposure to immunomodulators 100 100 Cumulative incidence of exposure to bologics 75 p>0.05 p<0.05 75 50 50 25 25 0 0 Time (months) Time (months) 1-2 (%) 29 42 46 52 1-2 (%) 5 8 12 20 3-5 (%) 31 41 46 50 3-5 (%) 13 19 24 30 100 p>0.05 Cumulative incidence of surgery 75 50 25 0 Time (months) 1-2 (%) 4 4 7 9 3-5 (%) 7 9 10 12 Figure 3. Cumulative incidence of treatments in Crohn’s disease (CD) based on hospital categories: lower resources (1 and 2) vs. higher resources (3–5). J. Clin. Med. 2021, 10, 2885 14 of 19 Figure 4. Cumulative incidence of exposure to treatments in ulcerative colitis based on hospital categories: low endowed (1 and 2) vs. highly endowed (3-5). 100 100 Cumulative incidence of exposure to systemic steroids Cumulative incidence of exposure to mesalamine 75 75 p>0.05 p>0.05 50 50 25 25 0 0 Time (months) Time (months) 1-2 (%) 80 80 80 99 1-2 (%) 19 25 26 29 3-5 (%) 71 79 81 94 3-5 (%) 24 27 28 29 100 Cumulative incidence of exposure to immunomodulators 100 Cumulative incidence of exposure to bologics 75 p>0.05 75 p>0.05 50 50 25 25 0 0 Time (months) Time (months) 1-2 (%) 9 10 13 14 1-2 (%) 2 2 2 7 3-5 (%) 5 7 9 11 3-5 (%) 4 5 7 9 100 p>0.05 Cumulative incidence of surgery 75 50 25 0 Time (months) 1-2 (%) 2 2 2 2 3-5 (%) 0 0 0 0 Figure 4. Cumulative incidence of treatments in ulcerative colitis based on hospital categories: low resources (1 and 2) vs. higher resources (3–5). J. Clin. Med. 2021, 10, 2885 15 of 19 Table 5. Prevalence of exposure to different drug treatments, surgery and hospitalizations based on hospital categories. Low Resources High Resources (Categories 1–2) (Categories 3–5) p n = 177 n = 3434 Mesalamine ever, n (%) 136 (77) 2314 (67.4) <0.01 Steroids ever, n (%) 102 (58) 1814 (53) >0.05 Systemic steroid therapy, n (%) 53 (30) 1199 (35) >0.05 Immunomodulators, n (%) 56 (32) 880 (26) >0.05 Biologics, n (%) 22 (12) 536 (16) >0.05 Surgery, n (%) 8 (4.5) 191 (5.6) >0.05 Hospital admissions, n (%) 39 (22) 973 (28) >0.05 4. Discussion In this population-based study we evaluated the incidence, clinical characteristics and treatment choices in newly diagnosed IBD patients. To our knowledge, this is one of the largest studies on IBD epidemiology, and provides a comprehensive analysis of the current characteristics, treatments, surgery and hospitalization in a Southern European country. This study will be a helpful resource for researches and caregivers to understand the epidemiology, the clinical characteristics and the treatments choices in the biologics era. Our main finding was that the incidence of IBD in Spain was 16.2 cases per 100,000 inhabitant-years, considerably higher than previously described in Spain and even higher that previously reported in Western European countries [2,19]. For instance, in the 2011 inception cohort of the EpiCom study, the incidence of IBD was 7.2 cases/100,000 person- years in Greece, 10.5 in Italy, and 11.8 in Portugal. We have confirmed the results of previous studies, showing that the median diagnosis delay was 3 months and was significantly higher for CD than for UC [20,21]. In addition, we have been able to assess whether the delay depends on the time from the symptoms onset to the consultation with the primary care physician or on the access to the gastroenterologist. When we split the overall diagnosis delay into patient-dependent and physician-dependent intervals, we found that the first one was longer. In a study performed by Cantoro et al. in an Italian population, authors found similar results: time from symptoms onset to first consultation was about 3 times longer than time from first consultation to diagnosis. Authors suggested that the high prevalence of irritable bowel syndrome-like symptoms at IBD onset may be responsible for the underestimation of IBD symptoms by patients, leading to longer time to first consultation, while higher awareness of the disease once the patient consults with the physician might help to shorten delayed diagnosis [20]. Another major finding in our study is the high proportion of exposure of our popula- tion to immunomodulators and biological agents, much higher than previously reported. This finding is of great importance due to the high costs associated with IBD management. Several studies have observed a marked increase in the use of immunosuppressive and bio- logical drugs in previous decades [22]. For instance, in the EpiCom cohort, 12% of patients with CD in Western Europe received immunomodulators at 12 months after diagnosis, and 66% at 5 years. Regarding biological agents, 19% of CD patients received biological drugs at 12 months and 33% at 5 years after diagnosis in the EpiCom cohort. In the case of UC, 5 years after the diagnosis, 29% had been exposed to immunomodulators and 11% to biological drugs. In contrast, in our cohort, over 25% of patients received immunomodulators and over 15% biological drugs in the first year after IBD diagnosis. Furthermore, these figures were higher in CD than in UC. In this sense, one year after diagnosis, as much as 50% of CD patients and 11% of UC patients had used immunomodulators. Similarly, 29% of CD and 8% of UC patients were treated with biological drugs. Newer therapeutic algorithms that aim J. Clin. Med. 2021, 10, 2885 16 of 19 to achieve mucosal healing instead of only symptomatic control are probably increasing the use of biological therapies among patients [23]. Our results might represent more accurately the current use of IBD therapeutic choices by unselected gastroenterologists. Two recent publications have shown that IBD-related healthcare costs, in both Eu- rope and North America, are mainly attributable to medical costs, primarily biological drugs [5,6]. In the EpiCom cohort, with lower use of biologic than in our cohort, authors found an increase in expenditure on biologics during the 5-year follow-up. Biologics costs accounted for 73% of costs in CD and 48% in UC, with a mean cost per patient-year for biologics of 866 euros [6]. In Canada, in the decade between 2005 and 2015, the annual costs of care ascribed to IBD management nearly tripled (from $14.1 M to $38.7 M). Most of this increase was attributable to the rising costs of anti-TNF drug prescription. For an adequate allocation of resources, policy makers and managers in the context of a universal publicly funded health system should be aware of IBD burden when planning the costs of care for these patients. To the best of our knowledge, our study is the first showing treatment differences in patients with CD depending on hospital complexity. Use of biological drugs was higher in hospitals with high resources than in those with lower resources. It is unlikely that this is due to a selection bias of the most complex patients in hospitals with higher resources, since the patients have been treated in the same hospital since the disease was diagnosed, when the clinical evolution was not fully predictable yet. Rather, it may be due to greater “aggressiveness” of treatment to control the disease in these centers, as is also reflected in more frequent use of systemic corticosteroids and less use of mesalamine in patients with CD. Biological drugs seem to be associated, at least in the short term, with a lower need for surgery and hospital admissions [24]. However, long-term results, in real-life populations, are more controversial. Some studies have observed a decrease in the need for hospital admissions and surgery associated with an increase in the use of biological drugs, while other studies have not confirmed these differences [5,22,25–28]. In our study, a third of the patients required hospital admission during the first year from diagnosis, and 5.5% underwent at least one surgical intervention (11% in CD). Our results are in line with other previously reported results [25,26]. Despite higher use of biologics in hospitals with higher resources, we found no differences in the risk of surgery in comparison with centers with lower resources. However, the results of our study correspond to the first year since diagnosis; follow-up of the EpidemIBD cohort is ongoing until completing 5 years from diagnosis, which will allow us to know if early treatment with immunosuppressive and biological drugs is associated with a change in the natural history of the disease. Our study has several limitations. The number of centers located in rural areas and the number of hospitals with less resources was low; however, due to the large number of participating centers we could compare the incidence of IBD and the management of IBD in different types of hospitals. In addition, the registry lacks of data on clinical and endoscopic severity; however, to assess the appropriateness of immunomodulators and biologics use was not an aim of our study. At the time of the present analysis, patient follow-up was limited to one year and it was not possible to assess whether the use of immunomodulators and biologics had an impact on the natural history of the disease. The EpidemIBD registry is ongoing, as patient follow-up will last 5 years. Therefore, we will be able to assess the impact of biological and immunosuppressive treatments on the evolution of the disease. The main strengths of the present study are the large number of participating centers (108 hospitals) and patients (3611), and the prospective inclusion and follow-up of patients diagnosed within well-defined administrative areas covering over 20 million adult inhabitants. Patients were followed-up in a standardized manner and were comparable in observation time. In addition, the full database was monitored remotely to resolve queries and ensure data quality. Finally, our study included unselected centers (not only reference hospitals with a high level of patient complexity but also regional hospitals), which provides an accurate representation of current IBD management. J. Clin. Med. 2021, 10, 2885 17 of 19 In conclusion, in this prospective population-based cohort, the incidence of IBD in a Southern European country is over 16 cases/100,000 person-years, higher than previously described in Spain and in other Western European countries. The use of biological drugs is much higher than previously reported, mainly in CD patients and in hospitals with high resources. The EpidemIBD study underscores the importance of IBD in healthcare systems, which have to manage this complex disease. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/jcm10132885/s1, Supplementary Table S1. Incidence rates (cases/100,000 person-years) for inflammatory bowel disease by Autonomous Community in Spain, 2017; Supplementary Table S2. Extraintestinal manifestations at diagnosis in the inception cohort; Supplementary Table S3. Exami- nations performed at inflammatory bowel disease diagnosis; Supplementary Table S4. Reasons for hospitalizations in the first year after diagnosis; Supplementary Table S5. Patients’ characteristics based on hospital categories. Author Contributions: M.C. (María Chaparro) and J.P.G.: Study design, data collection, data analysis, data interpretation, writing the manuscript. A.G. (Ana Garre): Project management, data collection, data analysis, data interpretation. F.R.-A. and E.G.-E.: Study design, data analysis, data interpretation. Rest of authors: Patient inclusion, data interpretation and approval of the final version of the manuscript. All authors approved the final version of the manuscript. M.C. (María Chaparro) and J.P.G. are the guarantors of the article. All authors have read and agreed to the published version of the manuscript. Funding: This research has been funded by grants from the Instituto de Salud Carlos III (FIS grant PI16/01296 and PFI17/00143), a grant from GETECCU (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa) and MSD. Funding agencies had no role in the study design, in the writing of the manuscript or in the decision to submit for publication. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Hospital Universitario de La Princesa (protocol code GIS-2015-Incidencia; date of approval 12 November 2015). Informed Consent Statement: Patient consent was waived in patients included only for incidence calculation, in order to have an acute estimation of the incidence. Informed consent was obtained from all subjects who accepted to participate in the follow-up study. Data Availability Statement: The data underlying this article cannot be shared publicly due to the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author. Acknowledgments: The authors wish to express thanks to Almudena Durán and Paloma Jiménez for database monitoring and to Guillermo Ortega and Ancor Sanz for hospital clustering. Conflicts of Interest: M.C. has served as a speaker, or has received research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Phar-ma. J.M.B. has served as a speaker, a consultant and advisory member or has received research or education funding from Dr. Falk Pharma, Faes Farma, Ferring, Shire Pharmaceuticals, MSD, Abbvie, Takeda and Janssen. F.G. has received fees for educational activities and grants to attend conferences from Janssen, Takeda, Abbvie and MSD. His group receives research funding from MSD, Abbvie, Janssen, Takeda, and Tillots. J.M.D.A. has received grants to attend conferences from MSD, ABBVIE, Takeda, Falk. M Rivero as served as a speaker, a consultant and an advisory member for MSD, Abbvie, Janssen and Pfizer. R.F.-I. has served as a speaker for or has received research funding from Takeda, MSD, Abbvie, Janssen, Palex, Shire Pharmaceuticals, Til-lottsPharma. V.H. has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, FAES Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Otsuka Pharmaceutical, Pfizer, Takeda, Jansen, KernPharma Biologics, Gebro Pharma, Adacyte, Sandoz and Biogen. I.M.-J. has served as a speaker, consultant or advisory board member for Abbvie, Amgen, Biogen, Celltrion, Fresenius, Ferring, Dr. Falk Pharma, Hospira, Janssen, MSD, Otsuka Pharmaceutical, Pfizer, Sandoz, Shire Pharmaceuticals, Takeda and Tillotts Pharma. M.J.C. has received education funding from Pfizer, Takeda, Janssen, MSD, Ferring and Abbvie MD M.A. has received fees as a speaker, consultant and advisory member for and has received research funding from MSD, AbbVie, Hospira, Pfizer, J. Clin. Med. 2021, 10, 2885 18 of 19 Takeda, Janssen, Shire Pharmaceuticals, Tillotts Pharma, Faes Pharma. I.V. has served as speaker, consultant and advisory member for and has received funding from MSD, Abbvie, Pfizer, Ferring, Shire Pharmaceuticals, Takeda and Jannsen. I.N. has received fees as a speaker from Takeda and Janssen. J.P.G. has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma. Rest of authors have nothing to declare. Abbreviations Inflammatory bowel disease, IBD; Crohn’s disease, CD; ulcerative colitis, UC; inflammatory bowel disease unclassified, IBD-U; interquartile range, IQR. References 1. Kaplan, G.G. The global burden of IBD: From 2015 to 2025. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 720–727. [CrossRef] [PubMed] 2. Ng, S.C.; Shi, H.Y.; Hamidi, N.; Underwood, F.E.; Tang, W.; Benchimol, E.I.; Panaccione, R.; Ghosh, S.; Wu, J.C.Y.; Chan, F.K.L.; et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. Lancet 2018, 390, 2769–2778. 3. 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