title: Safety Profile of Thiopurines in Crohn Disease: Analysis of 893 Patient-Years Follow-Up in a Southern China Cohort.
abstract: Thiopurines have been associated with both clinical improvement and mucosal healing in treating Crohn disease (CD). Unfortunately, the high rate of adverse events (AEs) leading to drug withdrawal represents a major limitation in the use of these drugs.To evaluate the safety of thiopurines in patients with CD. To identify predictive factors associated with the development of thiopurine-induced AEs and withdrawal.This longitudinal cohort study examined patients from a university-based IBD referral center. Time-to-event analysis was performed with the Kaplan-Meier curve. Cox regression analysis was performed to identify potential predictive factors of AEs.Two hundred sixty-seven CD patients on thiopurines were included. A total of 143 AEs occurred at a median of 7.4 months (interquartile range, 3.7-15.3 months) after starting treatment. The cumulative incidence of AEs was 26%, with an annual risk of 4.3% per patient-year of treatment. The most frequent was leucopenia (41/267, 15.36%), followed by infections (29/267, 10.86%). Independent factors predictive of leucopenia were lower baseline hemoglobin (hazard ratio (HR), 0.34; 95% confidence interval (CI) 0.18-0.67) and the concomitant use of 5-aminosalicylic acid (HR, 3.05; 95% CI 1.44-8.76). Of the 28.44% (76/267) CD patients discontinued therapy, 14.61% due to AEs. A lower body mass index, the presence of extraintestinal manifestation, and the incidence of leucopenia independently predicted thiopurine withdrawal. In total, 37.5% of these patients restarted thiopurines and 52.3% of them had AEs again.About a quarter of patients on thiopurine therapy had AEs during follow-up and 1 of 7 patients had to discontinue thiopurines due to AEs.
authors.affiliation: From the Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
authors.forename: Ren
authors.initials: R
authors.lastname: Mao
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Zhang
authors.forename: Man-Ying
authors.initials: MY
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Bai-Li
authors.initials: BL
authors.lastname: Chen
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zeng
authors.forename: Min-Hu
authors.initials: MH
authors.lastname: Chen
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D002681:China; D003424:Crohn Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D012044:Regression Analysis; D012189:Retrospective Studies; D012959:Socioeconomic Factors
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine