Duke Clinical Research Institute, Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill.
JAMA. 2020 Feb 4;323(5):432-443. doi: 10.1001/jama.2019.22450.
Intravenous iron enables rapid correction of iron-deficiency anemia, but certain formulations induce fibroblast growth factor 23-mediated hypophosphatemia.
To compare risks of hypophosphatemia and effects on biomarkers of mineral and bone homeostasis of intravenous iron isomaltoside (now known as ferric derisomaltose) vs ferric carboxymaltose.
DESIGN, SETTING, AND PARTICIPANTS: Between October 2017 and June 2018, 245 patients aged 18 years and older with iron-deficiency anemia (hemoglobin level ≤11 g/dL; serum ferritin level ≤100 ng/mL) and intolerance or unresponsiveness to 1 month or more of oral iron were recruited from 30 outpatient clinic sites in the United States into 2 identically designed, open-label, randomized clinical trials. Patients with reduced kidney function were excluded. Serum phosphate and 12 additional biomarkers of mineral and bone homeostasis were measured on days 0, 1, 7, 8, 14, 21, and 35. The date of final follow-up was June 19, 2018, for trial A and May 29, 2018, for trial B.
Intravenous administration of iron isomaltoside, 1000 mg, on day 0 or ferric carboxymaltose, 750 mg, infused on days 0 and 7.
The primary end point was the incidence of hypophosphatemia (serum phosphate level <2.0 mg/dL) between baseline and day 35.
In trial A, 123 patients were randomized (mean [SD] age, 45.1 [11.0] years; 95.9% women), including 62 to iron isomaltoside and 61 to ferric carboxymaltose; 95.1% completed the trial. In trial B, 122 patients were randomized (mean [SD] age, 42.6 [12.2] years; 94.1% women), including 61 to iron isomaltoside and 61 to ferric carboxymaltose; 93.4% completed the trial. The incidence of hypophosphatemia was significantly lower following iron isomaltoside vs ferric carboxymaltose (trial A: 7.9% vs 75.0% [adjusted rate difference, -67.0% {95% CI, -77.4% to -51.5%}], P < .001; trial B: 8.1% vs 73.7% [adjusted rate difference, -65.8% {95% CI, -76.6% to -49.8%}], P < .001). Beyond hypophosphatemia and increased parathyroid hormone, the most common adverse drug reactions (No./total No.) were nausea (iron isomaltoside: 1/125; ferric carboxymaltose: 8/117) and headache (iron isomaltoside: 4/125; ferric carboxymaltose: 5/117).
In 2 randomized trials of patients with iron-deficiency anemia who were intolerant of or unresponsive to oral iron, iron isomaltoside (now called ferric derisomaltose), compared with ferric carboxymaltose, resulted in lower incidence of hypophosphatemia over 35 days. However, further research is needed to determine the clinical importance of this difference.
ClinicalTrials.gov Identifiers: NCT03238911 and NCT03237065.
重要性：静脉铁剂能够快速纠正缺铁性贫血，但某些配方会引起成纤维细胞生长因子 23 介导的低磷血症。
目的：比较静脉注射异麦芽糖铁（现称铁去麦芽糖铁）与羧基麦芽糖铁治疗缺铁性贫血（血红蛋白水平≤11g/dL；血清铁蛋白水平≤100ng/mL）且不耐受或对 1 个月以上口服铁剂无反应的患者发生低磷血症的风险，以及对矿物质和骨代谢生物标志物的影响。
设计、地点和参与者：2017 年 10 月至 2018 年 6 月期间，在美国 30 个门诊站点共招募了 245 名年龄在 18 岁及以上、有缺铁性贫血（血红蛋白水平≤11g/dL；血清铁蛋白水平≤100ng/mL）且对 1 个月或更长时间口服铁剂不耐受或无反应的患者，参与了两项设计相同、开放标签、随机临床试验。排除了肾功能受损的患者。在第 0、1、7、8、14、21 和 35 天测量血清磷和 12 种其他矿物质和骨代谢生物标志物。试验 A 的最后随访日期为 2018 年 6 月 19 日，试验 B 的最后随访日期为 2018 年 5 月 29 日。
干预措施：第 0 天静脉给予异麦芽糖铁 1000mg，或第 0 和 7 天给予羧基麦芽糖铁 750mg。
主要结局和测量指标：主要终点是基线至第 35 天之间低磷血症（血清磷水平<2.0mg/dL）的发生率。
结果：在试验 A 中，123 名患者被随机分配（平均[标准差]年龄，45.1[11.0]岁；95.9%为女性），其中 62 名患者接受异麦芽糖铁治疗，61 名患者接受羧基麦芽糖铁治疗；95.1%的患者完成了试验。在试验 B 中，122 名患者被随机分配（平均[标准差]年龄，42.6[12.2]岁；94.1%为女性），其中 61 名患者接受异麦芽糖铁治疗，61 名患者接受羧基麦芽糖铁治疗；93.4%的患者完成了试验。异麦芽糖铁组的低磷血症发生率明显低于羧基麦芽糖铁组（试验 A：7.9%比 75.0%[调整后发生率差异，-67.0%（95%CI，-77.4%至-51.5%]，P<.001；试验 B：8.1%比 73.7%[调整后发生率差异，-65.8%（95%CI，-76.6%至-49.8%]，P<.001）。除低磷血症和甲状旁腺激素升高外，最常见的药物不良反应（发生例数/总例数）为恶心（异麦芽糖铁：1/125；羧基麦芽糖铁：8/117）和头痛（异麦芽糖铁：4/125；羧基麦芽糖铁：5/117）。
结论和相关性：在 2 项不耐受或无反应口服铁剂的缺铁性贫血患者的随机试验中，与羧基麦芽糖铁相比，异麦芽糖铁（现称铁去麦芽糖铁）在 35 天内导致低磷血症的发生率较低。然而，仍需要进一步的研究来确定这种差异的临床重要性。
试验注册：ClinicalTrials.gov 标识符：NCT03238911 和 NCT03237065。
