克罗恩病患者贫血的治疗及生活质量改善:使用羧基麦芽糖铁的经验

TREATMENT OF ANEMIA AND IMPROVEMENT OF QUALITY OF LIFE AMONG PATIENTS WITH CROHN'S DISEASE: experience using ferric carboxymaltose.

作者信息

Sobrado Carlos Walter, Cançado Rodolfo Delfini, Sobrado Lucas Faraco, Frugis Marcos Onofre, Sobrado Marcel Faraco

机构信息

Centro de Doenças Anorretais, Hospital 9 de Julho, São Paulo, SP, Brasil.

Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.

出版信息

Arq Gastroenterol. 2015 Dec;52(4):255-9. doi: 10.1590/S0004-28032015000400002.

Abstract

OBJECTIVES

Anemia is the most common hematological alteration in patients with Crohn's disease, and is frequently related to intestinal inflammatory activity. Its cause is multifactorial and mostly associated with absolute iron deficiency (iron deficiency anemia) and/or functional iron deficiency (inflammation anemia or anemia of chronic disease). It may also be identified through other causes, such as folic acid or vitamin B12 deficiency and secondary to adverse effects from medications (salicylic derivatives and immunosuppressive drugs). In the present study, patients with active Crohn's disease and anemia were evaluated and treated with intravenous ferric carboxymaltose. We discuss the therapeutic schemes (doses), safety, results and improvement of quality of life.

METHODS

In the present prospective study, 10 consecutive patients with Crohn's disease, with moderate to severe activity, with anemia (Hb: 6.7 to 10 g/dL), who were attended between March 2014 and March 2015, were evaluated. Six (60%) were men and four were women, all with moderate or severe anemia (hemoglobin <10 g/dL). They were treated with a maximum of three intravenous infusions of 1000 mg of ferric carboxymaltose, of at least 15 minutes in duration. It was also sought to correlate the inflammatory Crohn's disease activity degree (measured using the Crohn's Disease Activity Index, CDAI) and C-reactive protein level with the severity of anemia. The primary outcome was an increase in Hb of ≥2 g/dL and the secondary outcome was the normalization of anemia (Hb ≥12 g/dL for women and ≥13 g/dL for men) and the improvement in quality of life seen 12 weeks after the last application of carboxymaltose.

RESULTS

Among the 10 patients studied, parenteral iron supplementation was administered in three cases during hospitalization and the others received this on an outpatient basis. The total iron dose ranged from 1,000 to 2,000 mg, with an average of 1,650 mg. Crohn's disease activity measured using CDAI and C-reactive protein correlated with the intensity of anemia. An increase of 2 g/dL occurred in eight (80%) patients after 12 weeks and normalization of anemia was found in seven (70%) patients. Improvements in quality-of-life scores were found for all (100%) patients after 12 weeks. Carboxymaltose was well tolerated. Three patients presented adverse reactions (two with nausea and one with headache) of mild intensity.

CONCLUSIONS

Anemia is a frequent complication for Crohn's disease patients. Intravenous iron therapy has been recommended for Crohn's disease patients, because for these patients, oral iron absorption is very limited. This is because of the inflammatory state and "blocking" of iron entry into enterocytes through hepcidin action on ferroportin, along with the elevated rates of gastrointestinal adverse events that compromise adherence to treatment and possibly aggravate the intestinal inflammatory state. The degree of Crohn's disease activity, as measured using CDAI and C-reactive protein, correlates with the severity of anemia. Carboxymaltose is a safe drug, which can be administrated in high doses (up to 1,000 mg per application per week) and corrects anemia and iron stocks over a short period of time, with consequent improvement in quality of life.

摘要

目的

贫血是克罗恩病患者最常见的血液学改变,且常与肠道炎症活动相关。其病因是多因素的,主要与绝对缺铁(缺铁性贫血)和/或功能性缺铁(炎症性贫血或慢性病贫血)有关。也可能由其他原因导致,如叶酸或维生素B12缺乏以及药物(水杨酸衍生物和免疫抑制药物)的不良反应。在本研究中,对患有活动性克罗恩病和贫血的患者进行了评估,并给予静脉注射羧基麦芽糖铁治疗。我们讨论了治疗方案(剂量)、安全性、结果以及生活质量的改善情况。

方法

在本前瞻性研究中,对2014年3月至2015年3月期间收治的10例连续性克罗恩病患者进行了评估,这些患者病情为中度至重度活动期且伴有贫血(血红蛋白:6.7至10g/dL)。其中6例(60%)为男性,4例为女性,均患有中度或重度贫血(血红蛋白<10g/dL)。他们接受了最多三次静脉输注1000mg羧基麦芽糖铁的治疗,每次输注持续至少15分钟。还试图将克罗恩病炎症活动度(使用克罗恩病活动指数,CDAI测量)和C反应蛋白水平与贫血严重程度相关联。主要结局是血红蛋白增加≥2g/dL,次要结局是贫血恢复正常(女性血红蛋白≥12g/dL,男性血红蛋白≥13g/dL)以及在最后一次应用羧基麦芽糖铁12周后生活质量得到改善。

结果

在研究的10例患者中,3例在住院期间接受了胃肠外铁补充治疗,其他患者在门诊接受治疗。总铁剂量范围为1000至2000mg,平均为1650mg。使用CDAI和C反应蛋白测量的克罗恩病活动度与贫血强度相关。12周后,8例(80%)患者血红蛋白增加了2g/dL,7例(70%)患者贫血恢复正常。12周后所有(100%)患者的生活质量评分均有改善。羧基麦芽糖铁耐受性良好。3例患者出现轻度不良反应(2例恶心,1例头痛)。

结论

贫血是克罗恩病患者常见的并发症。对于克罗恩病患者推荐静脉铁剂治疗,因为这些患者口服铁吸收非常有限。这是由于炎症状态以及通过铁调素对铁转运蛋白的作用“阻断”了铁进入肠细胞,同时胃肠道不良事件发生率较高,这会影响治疗依从性并可能加重肠道炎症状态。使用CDAI和C反应蛋白测量的克罗恩病活动度与贫血严重程度相关。羧基麦芽糖铁是一种安全的药物,可以高剂量给药(每周每次应用高达1000mg),并在短时间内纠正贫血和铁储备,从而改善生活质量。

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