Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine

Guillermo Bastida; Diego Alvarez-Sotomayor; Mariam Aguas; Marisa Iborra; Javier Del Hoyo; Sergio Béjar-Serrano; Alejandro Garrido-Marín; Elena Valero-Pérez; Pilar Nos

doi:10.1016/j.gastrohep.2023.12.001

Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine

Gastroenterol Hepatol. 2023 Dec 10:S0210-5705(23)00491-0. doi: 10.1016/j.gastrohep.2023.12.001. Online ahead of print.

[Article in English, Spanish]

Authors

Guillermo Bastida¹, Diego Alvarez-Sotomayor², Mariam Aguas³, Marisa Iborra³, Javier Del Hoyo³, Sergio Béjar-Serrano³, Alejandro Garrido-Marín³, Elena Valero-Pérez⁴, Pilar Nos³

Affiliations

¹ Medicina Digestiva, Sección de Gastroenterología, Hospital Universitari i Politècnic La Fe, Avenida Fernando Abril Martorell 106, 46020 Valencia, Spain. Electronic address: guille.bastida@gmail.com.
² Medicina Digestiva, Hospital Verge de la Cinta, Carrer de les Esplanetes, 44-58, 43500 Tortosa, Tarragona, Spain.
³ Medicina Digestiva, Sección de Gastroenterología, Hospital Universitari i Politècnic La Fe, Avenida Fernando Abril Martorell 106, 46020 Valencia, Spain.
⁴ Medicina Interna, Sección de Digestivo, Hospital Universitario de La Ribera, Km 1, Ctra. Corbera, 46600 Alzira, Valencia, Spain.

PMID: 38072359
DOI: 10.1016/j.gastrohep.2023.12.001

Abstract

Background: Thiopurines such as azathioprine (AZA) and mercaptopurine (MP) are commonly utilized to treat inflammatory bowel disease (IBD). Their use is frequently restricted due to gastrointestinal intolerance (GI). Previous retrospective studies have reported that AZA-intolerant patients may benefit from a switch to MP; yet the effectiveness of this strategy has not been prospectively evaluated.

Aims: To assess GI tolerance to MP in patients who are intolerant to AZA, and to identify clinical predictors of GI intolerance to AZA or MP.

Methods: A prospective, observational, single-cohort study was performed in 92 thiopurine-naïve IBD patients. They were started on a 50mg dose of AZA and escalated to 2.5mg/kg per day by week 2. Those with GI intolerance were rechallenged with a 50% dose of AZA, after which another dose escalation attempt was made. If symptoms persisted, they were switched to MP.

Results: Thirty (32.6%) of the recruited patients suffered from GI intolerance to AZA. Of these, 15 did not present recurrence of symptoms after rechallenge with lower doses. Of 15 intolerant patients, 14 were switched to MP. Within the MP cohort, 8 patients (57%) were also intolerant to MP, 5 (36%) had no symptoms, and 1 (7%) was lost to follow-up. Female gender was the only independent predictor of GI intolerance to AZA.

Conclusions: Up to half of the AZA-intolerant patients tolerated a 50% dose rechallenge that was successfully escalated. A switch to MP was tolerated in over a third of cases whom rechallenge failed. Our strategy (challenge-rechallenge-switch) achieved an overall GI tolerance to thiopurines in most of the patients.

Keywords: Adverse events; Azathioprine; Azatioprina; Enfermedad inflamatoria intestinal; Eventos adversos; Inflammatory bowel disease; Intolerance; Intolerancia; Mercaptopurina; Mercaptopurine; Thiopurines; Tiopurinas.