Macaluso Fabio Salvatore, Renna Sara, Maida Marcello, Dimarco Mariangela, Sapienza Chiara, Affronti Marco, Orlando Emanuele, Rizzuto Giulia, Orlando Rosalba, Ventimiglia Marco, Cottone Mario, Orlando Ambrogio
a Di.Bi.M.I.S., Division of Internal Medicine , "Villa Sofia-Cervello" Hospital, University of Palermo , Palermo , Italy.
b Gastroenterology and Endoscopy Unit , "Villa Sofia-Cervello" Hospital , Palermo , Italy.
Scand J Gastroenterol. 2017 Sep;52(9):981-987. doi: 10.1080/00365521.2017.1333626. Epub 2017 May 29.
The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.
All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.
Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p = .01 and p = .03, respectively), and occurrence of nausea with Crohn's disease (p = .04).
Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.
硫嘌呤相关不良事件（AE）的发生可能会使炎症性肠病（IBD）患者的管理变得复杂。我们旨在评估在当前IBD背景下硫嘌呤的耐受性。
将2010年1月至2016年3月开始使用硫唑嘌呤（AZA）治疗的所有连续患者纳入一个前瞻性维护的数据库，并报告导致药物永久停用的AE。
共纳入253例患者。中位总随访时间为32个月（范围：0.2 - 75个月）。在研究结束时，160例患者（63.2%）停用了AZA。导致停药的主要原因是AE的发生（109/160例患者[68.1%]；整个队列中的累积发生率：43.1%）。总体而言，导致治疗停药的最常见AE是恶心（253例患者中的31例，12.3%）和主观症状，即定义不明确的副作用，如疲劳、头痛和肌肉疼痛（253例患者中的20例，7.9%）。在109例对AZA不耐受的患者中，44例（40.4%）换用了6 - 巯基嘌呤（6 - MP）。在随访结束时，44例患者中的35例（79.5%）停用了6 - MP，主要是由于AE（35例患者中的29例，82.8%）。硫唑嘌呤引起的肝脏和胰腺毒性与男性性别相关（分别为p = 0.01和p = 0.03），恶心的发生与克罗恩病相关（p = 0.04）。
我们的真实生活前瞻性队列显示，与迄今报道的相比，因AE导致硫嘌呤停药的累积发生率更高。从AZA换用6 - MP通常无效。
