Switching to a second thiopurine in adult and elderly patients with inflammatorybowel disease: a nationwide study from the ENEIDA registry

Calafat M1,2, Mañosa M1,2,3, Mesonero F4, Guardiola J5, Mínguez M6, Nos P3,7, Vera I8, Taxonera C9, Iglesias E10, Ricart E3,11, Gisbert JP3,12, Calvet X3,13, García-López S14, Monfort D15, Pérez Calle JL16, Riestra S17, Gomollón F3,18, Garcia-Planella E19, Bermejo F20, Vicent H21, Martín-Arranz MD22, Gutiérrez A3,23, Torres P1, Cañete F1,2,3, Domènech E1,2,3. J Crohns Colitis. 2020 Mar 23. pii: jjaa055. doi: 10.1093/ecco-jcc/jjaa055. [Epub ahead of print]


Author information

1 Hospital Universitari Germans Trias i Pujol (Badalona).

2 Departament de Medicina, Universitat Autònoma de Barcelona (Barcelona).

3 Centro de Investigación Biomédica en Red sobre enfermedades Hepáticas y Digestivas CIIBEREHD.

4 Hospital Universitario Ramón y Cajal (Madrid).

5 Hospital Universitari de Bellvitge, IDIBELL, (L'Hospitalet del Llobregat) Universitat de Barcelona (Barcelona).

6 Hospital Clínico de Valencia, Universitat de València (Valencia).

7 Hospital Universitari i Politècnic La Fe (Valencia).

8 Hospital Universitario Puerta de Hierro (Majadahonda).

9 Hospital Clínico San Carlos (Madrid).

10 Hospital Reina Sofía (Córdoba).

11 Hospital Clínic, IDIBAPS (Barcelona).

12 Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (Madrid).

13 Hospital Parc Taulí (Sabadell).

14 Hospital Universitario Miguel Servet (Zaragoza).

15 Consorci Sanitari de Terrassa (Terrassa).

16 Hospital Universitario Fundación de Alcorcón (Alcorcón).

17 Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) (Oviedo).

18 Hospital Clínico Lozano Blesa,  IIS Aragón (Zaragoza).

19 Hospital de la Santa Creu i Sant Pau (Barcelona).

20 Hospital Universitario Fuenlabrada (Fuenlabrada) and Instituto de Investigación Sanitaria Hospital La Paz (IdiPAZ).

21 Complexo Hospitalario Universitario de Vigo (Vigo) and Gastrointestinal Diseases Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur). SERGAS-UVIGO.

22 Hospital Universitario La Paz (Madrid).

23 Hospital General Universitario de Alicante (Alicante).


BACKGROUND AND AIMS: Although commonly used in inflammatory bowel disease (IBD), thiopurines frequently cause intolerance and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort and to assess the impact of age on tolerance.

METHODS: Adult IBD patients from the ENEIDA registry who were switched to a second thiopurine due to adverse events (excluding malignancies and infections) were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18-50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance and persistence with the second thiopurine were evaluated.

RESULTS: A total of 1,278 patients (13% over 60 years of age) were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, while persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (OR 1.49; 95%CI 1.07-2.07; P=0.017), previous gastrointestinal toxicity (OR 1.4; 95%CI 1.11-1.78; P=0.005), previous acute pancreatitis (OR 6.78; 95%CI 2.55-18.05; P<0.001), and exposure to the first thiopurine <6 months (OR 1.59; 95%CI 1.14-2.23; P=0.007).

CONCLUSIONS: In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended.

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