P541 Diagnosis, management, and evolution of acute pancreatitis secondary to thiopurines in patients with Inflammatory Bowel Disease: an ENEIDA registry study.

Guerra Marina, I.(1)*;Barros, F.(2);Mesonero, F.(3);de Francisco, R.(4);Cañete, F.(5,6);Benítez, J.M.(7);Sicilia, B.(8);Martín Arranz, M.D.(9);de Castro, L.(10);Carbajo, A.Y.(11);Gutiérrez, A.(6,12);Calvo, M.(13);Casanova, M.J.(6,14);González-Muñoza, C.(15);Miguel, M.(16);Alfambra, E.(6,17);Rivero, M.(18);Lucendo, A.J.(6,19);Tardillo, C.A.(20);Almela, P.(21);Bujanda, L.(6,22);Van Domselaar, M.(23);Ramos, L.(24);Fernández Sánchez, M.(25);Hinojosa, E.(26);Verdejo, C.(27);Gimenez, A.(28);Piqueras, M.(29);Rodríguez-Lago, I.(30);Manceñido, N.(31);Pérez Calle, J.L.(32);Moreno, M.D.P.(33);Delgado, P.G.(34);Antolín, B.(35);Ramírez de la Piscina, P.(36);Bermejo, F.(37);Carracedo, Á.(38);Domènech, E.(5,6);Gisbert, J.P.(6,14);

(1)Hospital Universitario de Fuenlabrada, Gastroenterology, Fuenlabrada, Spain;(2)Fundación Pública Galega de Medicina Xenómica. Sergas., Unidad de Medicina Molecular, Santiago de Compostela, Spain;(3)Hospital Universitario Ramón y Cajal, Gastroenterology, Madrid, Spain;(4)Hospital Universitario Central de Asturias- Instituto de Investigación Sanitaria del Principado de Asturias ISPA-, Gastroenterology, Oviedo, Spain;(5)Hospital Universitari Germans Trias i Pujol, Gastroenterology, Badalona, Spain;(6)Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHD, Gastroenterology, Spain, Spain;(7)Hospital Universitario Reina Sofía e Instituto Maimónides de Investigación Biomédica de Córdoba IMIBIC, Gastroenterology, Córdoba, Spain;(8)Hospital Universitario de Burgos, Gastroenterology, Burgos, Spain;(9)Hospital Universitario La Paz, Gastroenterology, Madrid, Spain;(10)Hospital Alvaro Cunqueiro-Complexo Hospitalario Universitario de Vigo- Instituto de Investigación Biomédica Galicia Sur, Gastroenterology, Vigo, Spain;(11)Hospital Universitario Rio Hortega, Gastroenterology, Valladolid, Spain;(12)Hospital General Universitario Dr Balmis de Alicante. ISABIAL., Gastroenterology, Alicante, Spain;(13)Hospital Universitario Puerta de Hierro-Majadahonda, Gastroenterology, Madrid, Spain;(14)Hospital Universitario de La Princesa- Instituto de Investigación Sanitaria Princesa IIS-Princesa- UAM, Gastroenterology, Madrid, Spain;(15)Hospital de la Santa Creu i Sant Pau, Gastroenterology, Barcelona, Spain;(16)Hospital Clínico Universitario de Valencia, Gastroenterology, Valencia, Spain;(17)Hospital Clínico Universitario “Lozano Blesa” e Instituto de Investigación Sanitaria de Aragón IIS Aragón, Hospital Clínico Universitario “Lozano Blesa” e Instituto de Investigación Sanitaria de Aragón IIS Aragón, Zaragoza, Spain;(18)Hospital Universitario Marqués de Valdecilla e IDIVAL, Gastroenterology, Santander, Spain;(19)Hospital General de Tomelloso, Gastroenterology, Ciudad Real, Spain;(20)Hospital Universitario Nuestra Señora Candelaria, Gastroenterology, Santa Cruz de Tenerife, Spain;(21)Hospital General Universitari de Castelló, Gastroenterology, Castelló, Spain;(22)Hospital Donostia/Instituto Biodonostia- Universidad del País Vasco UPV/EHU, Gastroenterology, Donostia/San Sebastián, Spain;(23)Hospital Universitario de Torrejón y Universidad Francisco de Vitoria, Gastroenterology, Madrid, Spain;(24)Hospital Universitario de Canarias, Gastroenterology, Santa Cruz de Tenerife, Spain;(25)Hospital General Universitario de Elche, Gastroenterology, Alicante, Spain;(26)Hospital de Manises, Gastroenterology, Valencia, Spain;(27)Hospital General Universitario de Ciudad Real, Gastroenterology, Ciudad Real, Spain;(28)Hospital Sant Joan de Déu-Althaia, Gastroenterology, Manresa, Spain;(29)Consorci Sanitari Terrasa, Gastroenterology, Terrasa, Spain;(30)Hospital de Galdakao, Gastroenterology, Galdakao, Spain;(31)Hospital Universitario Infanta Sofía, Gastroenterology, San Sebastián de los Reyes- Madrid, Spain;(32)Hospital Universitario Fundación Alcorcón, Gastroenterology, Madrid, Spain;(33)Hospital General La Mancha Centro, Gastroenterology, Alcázar de San Juan- Ciudad Real, Spain;(34)Hospital General de Granollers, Gastroenterology, Granollers, Spain;(35)Hospital Clínico Universitario de Valladolid, Gastroenterology, Valladolid, Spain;(36)Hospital Universitario de Áraba, Gastroenterology, Áraba, Spain;(37)Hospital Universitario de Fuenlabrada, Gastroenterology, Madrid, Spain;(38)Fundación Pública Galega de Medicina Xenómica. Sergas, Unidad de Medicina Molecular, Santiago de Compostela, Spain; On behalf of the ENEIDA project of GETECCU.


Treatment with thiopurines in patients with Inflammatory Bowel Disease (IBD) may be associated with different adverse effects, including acute pancreatitis. Our aims were to evaluate the clinical presentation, severity and management of acute pancreatitis related to thiopurines in patients with IBD.


IBD patients with acute pancreatitis secondary to treatment with thiopurines for IBD were identified from the prospectively maintained ENEIDA registry of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU).  We included those patients who met the Atlanta diagnostic criteria and had an imaging test that ruled out biliary origin of pancreatitis. Investigators at each participating centre provided additional information on pancreatitis clinical evolution and management.


We included 290 patients with pancreatitis in 34 centres; 54% were women, 84% had Crohn’s disease and 56% were smokers.  Five (1.7%) had had pancreatitis before, but no patient met criteria for chronic pancreatitis. The median age at pancreatitis was 36 years (IQR 27-50). In 94% of cases, pancreatitis occurred after the first thiopurine drug. Azathioprine was the thiopurine used in 97% of cases (median dose 2.3 mg/kg/day (IQR 2-2.5)), and 6% were treated with mercaptopurine (1.5 mg/kg/day (IQR 1-1.5)). Pancreatitis was diagnosed after a median of 23 days (IQR 14-35) since the start of the treatment with thiopurines. 81% required hospitalization for pancreatitis for a median of 5 days (IQR 4-7). Four (1.4%) were severe pancreatitis, 16 (5.5%) moderate, and the rest mild, according to the Atlanta classification. No epidemiological or treatment factors were associated with the severity of pancreatitis. Thiopurine was withdrawn in all patients upon diagnosis of pancreatitis. After 2 months (IQR 1-28) of pancreatitis, 16 patients (5.5%) received thiopurines again (5 the same, 11 a different thiopurine), suffering a new episode of pancreatitis in 12 (75%) after a median of 12 days (IQR 5-34). Pancreatitis occurred in all smokers that were treated again with thiopurines (n=7), compared to 5 of the 9 (56%) non-smokers or former smokers (p=0.04, RR 1.8; 95% CI 1.1-3.2).


Acute pancreatitis secondary to treatment with thiopurines is mild in most patients, usually appearing during the first month of treatment. The reintroduction of thiopurines, although feasible in some cases, is not recommended due to the high risk of developing a new pancreatitis, especially in smokers.