A Randomised Controlled Trial Comparing the Efficacy of Intravenous Iron Sucrose and Oral Iron Sulfate in Patients With Iron Deficiency.

1.1 Literature

Iron deficiency anemia is a common and a major management issue in Inflammatory Bowel disease [1-3]. Moreover, no factor has been identified in predicting recurrent iron deficiency anemia [4]. Iron deficiency and anemia are well recognized causes of fatigue, poor concentration and decreased energy level which impact on one's quality of life and ability to maintain employment or managing activities of daily living [2, 5]. Iron deficiency anemia is multi-factorial in origin and its causes can be divided into disease or patient origin. Disease factors include active blood loss from gastrointestinal mucosal ulceration, impairment of iron absorption if disease affects the proximal small bowels or a history of extensive small bowel resection. Iron absorption and utilization may also be influenced by inflammation inducible production of the hepatic origin peptide hormone called hepcidin [5], Interleukin 10 (IL10) [6] and interleukin 6 (IL 6) [7, 8]. Inflammatory cytokines such as Tumour Necrosis Factor alpha (TNFa) and IL-6 have been shown to cause anorexia in the animal model [9]. The major patient factor is dietary aversion of certain food in order to avoid exacerbation of existing symptom [10, 11].

Iron can be replaced either orally or intravenously. To date five studies directly compare oral versus intravenous iron therapy in patients with inflammatory bowel disease. Three of the studies suggested intravenous iron was superior [12-14], one suggested oral iron was superior [15]and one showed no difference[16]. This confusion is evident by a retrospective review of a gastroenterology outpatient clinic's experience in detecting and managing iron deficiency anaemia in both IBD and non IBD patients[17]. Furthermore, there are studies advocating the concurrent use of Erythropoietin which makes it difficult to draw a definite conclusion.

Studies have shown that iron deficient without anaemia is associated with reduced cognitive performance and it is reversible with iron supplementation.(18)19) In combination with other non specific symptoms such as fatigue and poor concentration span, many clinicians have been treating iron deficiency before anaemia occurs. Moreover, the World Health Organization (WHO) estimated the number of iron deficient people to be twice that of diagnosed anaemic people, (20) therefore, it is more appropriate to use iron deficiency as the inclusion criterion. This is in contrast with most of the clinical trials examining iron replacement therapy use iron deficiency anaemia as the inclusion criteria. The approach of stratifying the route of iron replacement therapy by the degree of anaemia is logical but not evidence based. This study seeks to investigate the efficacy of intravenous iron versus oral iron replacement in iron deficient patients.

Bone marrow biopsy staining for iron store is the gold standard for assessing iron store but it is invasive, therefore surrogate serum markers such as ferritin and iron saturation are used in clinical practice and they have been shown to be accurate.(21) Low ferritin level is associated with high (78%-100%) specificity and low iron saturation has a high sensitivity for iron deficiency (59%-88%). (22) Moreover, in anaemic IBD population, low ferritin level has >90% specificity for iron deficiency. (23) Given some of the IBD patients will have 'functional' iron deficiency with elevated ferritin and CRP and a low iron saturation, we have decided to use iron saturation <16% and ferritin less than 100ug/L to indicate iron deficient state. This cut off is consistent with the laboratory standard for University of Alberta Hospital.