The Potential of IV Iron Treatment in IBD Patients with Iron Deficiency Anemia
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PRIORITY PRESS - 8th Congress of the European Crohn’s and Colitis Organisation
Vienna, Austria / February 14-16, 2013
Vienna - Anemia is the most common complication of inflammatory bowel disease (IBD), iron deficiency anemia (IDA) being the most prevalent cause. Correction of iron deficiency and IDA in IBD patients reduces the associated fatigue and tiredness, factors related to quality of life. Several non-dextran IV iron formulations are being evaluated in IBD and results suggest they are safe and well tolerated, and increase hemoglobin in the majority of patients, increasing the rationale for IV rather than oral iron as the preferred treatment. Rapid delivery of some of the newer IV iron formulations is a step forward in convenience and in relieving symptoms of IDA in IBD.
Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec
According to Dr. Marte Lie Høivik, Oslo University Hospital, Norway, reduced quality of life (QoL) is observed in IBD patients with severe anemia and also in those with near normal hemoglobin (Hb) levels. In the IBSEN (Inflammatory Bowel Disease in South Eastern Norway) study using WHO definitions of anemia at diagnosis, anemia was reported in 50% of Crohn’s disease (CD) patients (n=225) and 21% of ulcerative colitis (UC) patients (n=465) (Abstract 28). Although the proportion of patients with anemia declined continuously during the 10-year follow-up, “These data underscore the importance of regular monitoring of anemia in all IBD patients,” Dr. Høivik stated.
Anemia—defined by World Health Organization (WHO) as a hemoglobin (Hb) <12 g/dL in women and <13 g/dL in men—manifests in approximately one-third of patients. Symptoms affecting QoL include fatigue, headache, dizziness and tachycardia as well as exertional and even resting dyspnea (Ann Gastroenterol 2012;26:1-10). Although anemia in IBD has multiple causes, the most frequent by far is iron deficiency anemia (IDA).
Treatment: A Patient Perspective
A patient perspective survey of 631 IBD patients was presented here by Hoffman et al. (Abstract P593). In approximately two-thirds, anemia had been diagnosed, and fatigue/tiredness was reported by 86% of the group. Fatigue had a major negative impact on daily life including physical activities, productivity and home life (76%, 63% and 60% respectively).
Treatments consisted of oral iron prescription (42%), intravenous (IV) iron (27%), non-prescription iron supplements (19%) and prescription liquid/syrup iron (10%). Primarily due to poor tolerability, most patients taking liquid/syrup iron (77%), oral iron (74%) and iron supplements (68%) were dissatisfied with their treatment. In contrast, 72% prescribed IV iron were satisfied with the treatment.
IV Iron Appropriateness
The first guidelines written specifically to address the issue of anemia in IBD patients were released in 2007 by Gasche et al., (Inflamm Bowel Dis 2007;13:1545-53). As the use of oral iron in IBD may be associated with disease exacerbation, these guidelines suggested that iron supplementation in IBD should be administered IV. Although 2010 guidelines from British Columbia state that oral iron replacement is preferred, IV therapy may be substituted when there is inadequate iron absorption, continued blood loss, noncompliance or intolerance to oral iron therapy (http://www.bcguidelines.ca/guideline_iron_deficiency.html).
Notably, a review of anemia management in the German AnemIBD study reported that only 43.5% of 193 IBD patients with diagnosed anemia had received some form of anti-anemic treatment in the 6 months prior to study inclusion (56% had received oral iron, 15% had received IV iron and 19% had received both oral and IV iron. While authors concluded that although IV administration of iron is recommended as the preferred route for IBD patients, current practice in Germany continues to rely on oral iron preparations (Abstract P552).
One explanation for the low use of IV iron may be due to the fact that until recently, the only IV iron formulations were low and high-molecular-weight iron dextrans, which carry a potential risk of anaphylactic reaction. Now, several dextran-free formulations have become available and have exhibited an excellent safety profile to date.
An international panel of experts used the RAND/University of California in Los Angeles Appropriateness Method (RUAM) to assess the appropriateness of different treatment regimens in patients both with IDA and those with iron deficiency without chemically manifest anemia (Abstract P435).
Treatment options included no active treatment, adjustment of IBD medication only, oral iron supplements, IV iron (both low and high-dose), IV iron plus erythropoietin stimulating agents and blood transfusions. It was concluded that “no treatment” was considered inappropriate and repeat treatment after previous failure was discouraged. Use of oral iron was mostly considered to be an option for iron deficient patients without biochemically manifest anemia provided they had previously been successful with this treatment. Of the IV regimens judged to be appropriate, high-dose IV iron was the preferred option in 77% of IDA scenarios.
“It’s my feeling that we are undertreating both anemia and iron deficiency, especially iron deficiency in IBD because we think there’s not much impact on QoL,” Dr. Laurent Peyrin-Biroulet, Head IBD, University Hospital, Vandoeuvre-lès-Nancy, France, stated. “Yet we know from other clinical conditions that it’s very important to treat iron deficiency, even when patients do not have anemia …and in clinical practice most patients should receive IV iron.”
Advances in IV Iron
In his private practice, Dr. David Hetzel, Clinical Senior Lecturer in Medicine, Royal Adelaide Hospital, Australia, has found IDA to be an “enormously common problem” among his own patients with IBD and identified IDA as a “QoL issue…and it’s not just tiredness and lethargy, it’s other symptoms such as restless leg syndrome that drive patients mad and which can be improved by supplementing patients with iron,” he remarked in an interview (as supported by Stein J, Dignass A. Ann Gastroenterol 2012;26:1-10).
In a randomized, controlled trial comparing the safety and efficacy of a 1-g course of IV ferumoxytol, 2 doses of 510 mg each given 2 to 8 days apart vs. 5 doses of iron sucrose 200 mg given over 14 days, Dr. Hetzel reported on a subgroup of 204 patients with IBD (138 on ferumoxytol and 66 on iron sucrose) and other causes of chronic gastrointestinal (GI) blood loss (Abstract P485) (Not approved for this indication in Canada). Results showed that 80% of patients in both arms had a >2 g/dL increase in Hb between baseline and week 5.
Increases in Hb occurred slightly more rapidly with the 2-dose approach compared with the 5-dose approach, Dr. Hetzel noted. Mean increases of 2.7 g/dL in Hb from baseline to week 5 for ferumoxytol were not inferior to mean increases of 2.5 g/dL for iron sucrose. Mean changes in transferrin saturation from baseline to week 5 were comparable at 12.7% for ferumoxytol and 10% for iron sucrose. Rates of serious adverse events (AEs) were also similar at 3.6% and 3%, respectively.
“There’s no doubt that oral iron preparations produce GI side effects—nausea, stomach pain, diarrhea in some and constipation in others—in patients with and without IBD,” Dr. Hetzel emphasized. “And when you are dealing with IBD, you really don’t want to confuse the issue by giving patients a drug that has similar adverse effects as the disease. So we are encouraged that ferumoxytol, even when given rapidly with relatively few injections, looks as though it’s safe.”
A 2-centre evaluation of IV ferric carboxymaltose in patients with IBD and IDA was reported by Millastre et al. (Not approved in Canada). Results showed that at 15 days, following 88 courses of IV iron, 63.6% had an increase in Hb although not normalization; 31.8% achieved a complete response and 4.6% had no increase in Hb (Abstract P494). At 90 days following 69 courses of IV iron, 81.1% achieved a complete response; Hb increased in another 14.6% but did not normalize, and 4.3% did not respond to treatment. Improvement in QoL as measured by the CCVEII-9 score correlated with Hb response. Only 1 AE required discontinuation of IV ferric carboxymaltose across the 88 courses of therapy.
A separate study by Jakobsen et al. also showed that ferric carboxymaltose, given as a single bolus of up to 500 mg within 2 minutes, is also safe and well tolerated in IBD patients and that it improves Hb among other indices of iron to an extent that is comparable to 500 mg of the same formulation given in a 15-minute IV infusion (Abstract P380).
Given that physicians have a mandate to improve QoL in IBD patients, correction of iron deficiency and IDA represents a major step forward in that direction. Studies have shown that patients respond well to IV iron formulations and the new dextran-free IV iron formulations are well tolerated and have demonstrated high efficacy and safety in this patient population. Well tolerated rapidly administered high dose IV formulations may be more convenient and acceptable for IBD patients with IDA.
Note: At time of print, ferumoxytol is indicated in Canada for the treatment of iron deficiency anemia in adult patients with chronic kidney disease.
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