Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AG&M Research Institute, Amsterdam, The Netherlands.
Aliment Pharmacol Ther. 2020 Jun;51(12):1353-1364. doi: 10.1111/apt.15734. Epub 2020 Apr 28.
To timely detect myelotoxicity and hepatotoxicity, laboratory monitoring at 3-month intervals is advised throughout thiopurine maintenance treatment for IBD. However, reported incidence rates of myelotoxicity and hepatotoxicity in maintenance treatment are low.
To assess incidence rates and clinical consequences of myelotoxicity and hepatotoxicity in thiopurine maintenance therapy after at least 1 year of thiopurine treatment.
Retrospective analysis of therapy adjustment for laboratory toxicity in adult IBD patients after 12 consecutive months of azathioprine (AZA) or mercaptopurine monotherapy (ie baseline) between 2000 and 2016. Incidence rates of laboratory toxicity (ie myelotoxicity [leucocyte count <4.0 × 10e9/L, and/or platelet count <150 × 10e9/L] and/or hepatotoxicity (gamma-glutamyltransferase [GGT], alkaline phosphatase [AP], ALT and/or AST above ULN, excluding isolated increased AST/AP]) and associated diagnostic procedures and complications were assessed.
In total, 12,391 laboratory assessments were performed on 1132 patients (56% female, AZA 74%) during 3.3 years of median follow-up. Median monitoring frequency was 3.1 assessments/treatment year. Only 83/12,391 (0.7%) assessments resulted in therapy adjustment, dose reduction in 46 patients, cessation in 28 and allopurinol initiation in nine; risk of therapy adjustment was 1.9% per treatment year. Incidence rates of myelotoxicity were 7.1% (5.1% mild/1.8% moderate/0.1% severe) and hepatotoxicity 5.1% (3.8% mild/1.1% moderate/0.2% severe) per treatment year. Treatment-related complications with concurrent laboratory toxicity occurred in 12 patients (1.1%) and would not have been prevented by monitoring.
Severe laboratory toxicity is uncommon after 1 year of thiopurine monotherapy at 4-month monitoring intervals. Therapy adjustments are rare after detection of laboratory toxicity. After 1 year of thiopurine monotherapy, laboratory monitoring may be lowered to less than a 4-month interval.
为了及时发现骨髓毒性和肝毒性，建议在使用硫嘌呤维持治疗 IBD 期间每 3 个月进行一次实验室监测。然而，维持治疗中骨髓毒性和肝毒性的报告发生率较低。
评估硫嘌呤维持治疗至少 1 年后硫嘌呤治疗中骨髓毒性和肝毒性的发生率和临床后果。
回顾性分析 2000 年至 2016 年间，12 例连续接受硫唑嘌呤（AZA）或巯嘌呤单药治疗（即基线）的成人 IBD 患者，在 12 个月后进行实验室毒性（即骨髓毒性[白细胞计数<4.0×10e9/L，和/或血小板计数<150×10e9/L]和/或肝毒性[γ-谷氨酰转移酶（GGT）、碱性磷酸酶（AP）、ALT 和/或 AST 高于 ULN，排除单独的 AST/AP 增加]）的治疗调整，并评估相关的诊断程序和并发症。
在中位随访 3.3 年期间，对 1132 例患者的 12391 次实验室评估中，共有 83 次（0.7%）评估导致治疗调整，46 例患者减少剂量，28 例停止治疗，9 例开始使用别嘌呤醇；治疗年的治疗调整风险为 1.9%。骨髓毒性的发生率为每年 7.1%（5.1%轻度/1.8%中度/0.1%重度），肝毒性的发生率为每年 5.1%（3.8%轻度/1.1%中度/0.2%重度）。在有实验室毒性的情况下，12 例患者（1.1%）出现与治疗相关的并发症，监测不能预防这些并发症。
在 4 个月监测间隔的硫嘌呤单药治疗 1 年后，严重的实验室毒性并不常见。在检测到实验室毒性后，治疗调整很少发生。在硫嘌呤单药治疗 1 年后，实验室监测可减少至不到 4 个月的间隔。
