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. 2019 Aug;50(4):407-415. doi: 10.1111/apt.15402.
Low-dose thiopurine-allopurinol (LDTA) combination therapy is a commonly applied optimisation strategy in IBD patients with a skewed thiopurine metabolism.
To assess continued LDTA maintenance treatment at annual intervals and explore risk factors for treatment cessation METHODS: Adult IBD patients treated with LDTA between 2009 and 2016 were retrospectively included. Data on the incidence of clinical and laboratory adverse events (AEs), including hepatotoxicity and myelotoxicity resulting in imposing LDTA therapy cessation and associated risk factors were collected.
In total, 221 IBD patients (46% male, median age 42 years) were included. Maintenance LDTA treatment was continued in 78% of patients at 1 year (n = 145), 66% at 2 years (n = 83), 57% at 3 years (n = 52) and 52% at 4 years (n = 33). Treatment in patients receiving LDTA therapy for AEs during thiopurine monotherapy was more often continued than in patients initiating LDTA for other indications (eg, ineffectiveness of thiopurine monotherapy, routinely discovered skewed metabolism) (P = 0.016). Myelotoxicity during thiopurine monotherapy resolved in 87% and hepatotoxicity in 86% after median of 1.2 and 1.4 months after LDTA initiation. Cumulative incidence of AEs during LDTA resulting in therapy cessation within total follow-up of 449 treatment-years was 7% for clinical AEs, 4% for myelotoxicity and 1% for hepatotoxicity.
LDTA therapy is a safe and beneficial optimisation strategy in IBD patients. Continued maintenance LDTA treatment is 52% after 4 years of treatment and most commonly affected by ineffectiveness of LDTA rather than LDTA-attributed toxicity. LDTA optimisation strategy is most advantageous in patients failing thiopurine monotherapy due to AEs.
低剂量巯嘌呤-别嘌呤醇（LDTA）联合治疗是一种常用于巯嘌呤代谢异常的 IBD 患者的优化策略。
评估每年一次的 LDTA 维持治疗，并探讨治疗终止的危险因素。
回顾性纳入 2009 年至 2016 年接受 LDTA 治疗的成年 IBD 患者。收集包括肝毒性和骨髓毒性导致 LDTA 治疗终止在内的临床和实验室不良事件（AE）的发生率，以及相关的危险因素。
共纳入 221 例 IBD 患者（46%为男性，中位年龄 42 岁）。1 年时（n=145）78%的患者继续维持 LDTA 治疗，2 年时（n=83）66%，3 年时（n=52）57%，4 年时（n=33）52%。在因 AE 接受 LDTA 治疗的患者中，继续治疗的比例高于因其他原因（如巯嘌呤单药治疗无效、常规发现代谢异常）开始 LDTA 治疗的患者（P=0.016）。巯嘌呤单药治疗期间发生的骨髓毒性在 LDTA 治疗开始后中位数 1.2 个月和 1.4 个月分别有 87%和 86%得到缓解。在 449 个治疗年的总随访期间，LDTA 相关 AE 导致治疗终止的累积发生率为临床 AE 7%，骨髓毒性 4%，肝毒性 1%。
LDTA 治疗是 IBD 患者安全有效的优化策略。在 4 年的治疗后，继续维持 LDTA 治疗的比例为 52%，最常见的原因是 LDTA 治疗无效，而不是 LDTA 相关毒性。在因 AE 而导致巯嘌呤单药治疗失败的患者中，LDTA 优化策略最具优势。
