背景:美沙拉嗪是炎症性肠病(IBD)中最常用的药物之一,尤其是溃疡性结肠炎.监管机构已将美沙拉嗪列为基于溶血风险的葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症受试者的不安全药物,虽然缺乏科学证据。评估了暴露于美沙拉嗪的G6PD缺乏症IBD患者的急性和/或慢性溶血性贫血的发生。
方法:在这项多中心研究中,G6PD缺乏的IBD患者(病例)接受美沙拉嗪进行回顾性评估,对于慢性,溶血。溶血性贫血的存在是基于红细胞和网织红细胞计数,血红蛋白,乳酸脱氢酶,未结合胆红素,和触珠蛋白水平。将病例与对照组(G6PD正常的IBD患者)进行比较。
结果:共纳入453例IBD患者(平均年龄52.1±16.0岁;58.5%为女性)。75%的患者存在溃疡性结肠炎。在17%的患者中检测到G6PD缺乏。67.9%的溃疡性结肠炎和32.4%的克罗恩病病例使用口服美沙拉嗪。78例接受美沙拉嗪治疗的G6PD缺乏症IBD患者均未接受急性溶血性贫血的住院治疗或特殊治疗。与接受美沙拉嗪(≤4500mg/天)的112例对照相比,在30例中未观察到慢性溶血标志物的相关差异。在无美沙拉嗪的病例中也观察到标志物修饰,与G6PD缺乏症的基础红细胞吞噬率一致。离体实验表明,在美沙拉嗪攻击后,缺乏G6PD的红细胞会释放高铁血红蛋白,仅高于2.5mg/mL,在临床环境中从未达到的浓度。
结论:这项研究提供了,第一次,证据表明,美沙拉嗪在G6PD缺乏症中的安全剂量高达4500毫克/天。
BACKGROUND: Mesalamine is one of the most-used drugs in inflammatory bowel disease (IBD), especially ulcerative colitis. Regulatory agencies have listed mesalamine as an unsafe drug in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency based on the risk of hemolysis, although scientific evidence is lacking. The occurrence of acute and/or chronic hemolytic anemia in IBD patients with G6PD deficiency exposed to mesalamine was evaluated.
METHODS: In this multicenter study, IBD patients with G6PD deficiency (cases) receiving mesalamine were retrospectively evaluated for acute, and prospectively for chronic, hemolysis. The presence of hemolytic anemia was based on red blood cell and reticulocyte count, hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and haptoglobin levels. Cases were compared with controls (IBD patients with normal G6PD).
RESULTS: A total of 453 IBD patients (mean age 52.1 ± 16.0 years; 58.5% female) were enrolled. Ulcerative colitis was present in 75% of patients. G6PD deficiency was detected in 17% of patients. Oral mesalamine was used in 67.9% of ulcerative colitis and in 32.4% of Crohn\'s disease cases. None of the 78 IBD patients with G6PD deficiency receiving mesalamine underwent hospitalization or specific treatment for acute hemolytic anemia. Relevant differences in chronic hemolysis markers were not observed in 30 cases compared with 112 controls receiving mesalamine (≤4500 mg/day). Marker modifications were also observed in mesalamine-free cases, consistent with the basal rate of erythrophagocytosis in G6PD deficiency. Ex vivo experiments showed the release of methemoglobin by G6PD deficient RBCs upon mesalamine challenge, only above 2.5 mg/mL, a concentration never reached in the clinical setting.
CONCLUSIONS: This study provides, for the first time, evidence that mesalamine is safe in G6PD deficiency at a dosage of up to 4500 mg/day.