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P424 Is the switch to a second thiopurine a safe strategy in elderly patients with inflammatory bowel disease? A multi-centre cohort study of the ENEIDA registry

M. Calafat*1, M. Mañosa1,2, E. Ricart2,3, E. Iglesias4, M. Calvo5, F. Rodríguez-Moranta6, C. Taxonera7, P. Nos2,8, F. Mesonero9, M. Martín-Arranz10, M. Mínguez11, J. P. Gisbert2,12, S. García-López13, R. de Francisco14, F. Gomollón2,15, X. Calvet2,16, E. García-Planella17, M. Rivero18, J. Martínez-Cadila19, F. Argüelles20, L. Arias21, M. Cimavilla22, Y. Zabana2,23, F. Cañete1,2, E. Cabré1,2, E. Domènech1,2, ENEIDA Registry of GETECCU1

1Hospital Universitari Germans Trias i Pujol, Gastroenterology Department, Badalona, Spain, 2CIBERehd, Madrid, Spain, 3Hospital Clínic, Barcelona, Spain, 4Hospital Reina Sofía, Córdoba, Spain, 5Hospital Puerta de Hierro, Majadahonda, Spain, 6Hospital de Bellvitge, L'Hospitalet del Llobregat, Spain, 7Hospital Clínico San Carlos, Madrid, Spain, 8Hospital La Fe de Valencia, Valencia, Spain, 9Hospital Ramón y Cajal, Madrid, Spain, 10Hospital La Paz, Madrid, Spain, 11Hospital Clínico de Valencia, Valencia, Spain, 12Hospital Universitario de La Princesa, Madrid, Spain, 13H.U. Miguel Servet, Zaragoza, Spain, 14H.U. Central de Asturias, Oviedo, Spain, 15H. Clínico Lozano Blesa, Zaragoza, Spain, 16H. Parc Taulí, Sabadell, Spain, 17H. Santa Creu i Sant Pau, Barcelona, Spain, 18H.U. Marqués de Valdecilla, Santander, Spain, 19Complexo H.U. de Vigo, Vigo, Spain, 20H. Virgen de la Macarena, Sevilla, Spain, 21H.U. Burgos, Burgos, Spain, 22H. Río Hortega, Valladolid, Spain, 23H. Mútua de Terrassa, Terrassa, Spain

Background

Thiopurines are the most commonly used immunosuppressants in inflammatory bowel disease (IBD), but their main limitation is the high rate of drug-related adverse events (AE) and treatment discontinuation. Switching to a second thiopurine may be an alternative in these cases, but series published up to now, include a limited number of patients. In a previous study, we demonstrated that starting thiopurines in elderly age is associated with a higher incidence of AE. Our aim was to evaluate the tolerance of switch to a second thiopurine as well as the persistence of treatment and the factors associated with it.

Methods

Based on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD—GETECCU), adult IBD patients that switch to a second thiopurine due to AE were identified. Two cohorts were selected regarding the age at the beginning of thiopurine treatment: between 18 and 50 years, and over 60 years. The rate and concordance of AE that occurred with the second thiopurine, treatment discontinuation due to AE and the overall persistence of the second thiopurine were evaluated.

Results

Of the 17371 patients who started a first thiopurine in these two cohorts, 3903 patients discontinued thiopurine treatment due to AE. In 1278 of them (32%) a switch to a second thiopurine was performed (93% to mercaptopurine, 7% to azathioprine), 1105 patients below 50 years of age and 173 over 60 years. The AE of the first thiopurine were: digestive intolerance 60%, hepatotoxicity 13%, myelotoxicity 6%, acute pancreatitis 2%, other 19%. The rate of post-switch AEs was 58%, leading to the discontinuation due to AE of the second-thiopurine in 46% of cases. In those patients who presented post-switch AE, the most likely AE was the same that occurred with the first thiopurine, particularly digestive intolerance (61%). The cumulative probability of post-switch treatment discontinuation due to AE was 40%, 43%, 47%, and 50% at 6 months, 1–3–5 years, respectively. The persistence of post-switch treatment was 44%, 40%, and 34% at 1–3–5 years, respectively. The multi-variate analysis showed that the only independent risk factors of treatment discontinuation due to AE were the switch over 60 years (53% vs. 45%, OR 1.5, 95% CI 1.1–2.1), having developed digestive intolerance (48% vs. 41%, OR 1.4, 95% CI 1.1–1.8) or pancreatitis (83% vs. 45%, OR 6.8, 95% CI 2.6–18.2) with the first thiopurine.

Conclusion

In the largest series reported to date, we observed that switch to a second thiopurine is a valid strategy except in the case of pancreatitis. Close monitoring is advisable among elderly IBD patients switching to a second thiopurines because of AEs.