Correcting iron deficiency in patients with inflammatory bowel disease (IBD) is now a lot simpler than it used to be, thanks to the availability of rapid iron infusion protocols to address this common issue.

The introduction of rapid iron infusion protocols has made it simpler to correct iron deficiency in patients with IBD, according to Professor Peter Gibson. This has resulted in clinicians more readily testing iron levels and correcting iron deficiency, to the benefit of patients, he says.

“It’s gratifying to see the improvement in patient wellbeing after addressing iron deficiency,” Professor Gibson says. “Patients feel the benefits quickly, and they’re usually very grateful for what you’ve done.” He suggests that any potential disadvantages of iron infusions – in terms of possible short-term flare-ups of inflammation – are outweighed by the advantages to quality of life. “If my patient mentions that their disease got worse immediately after an iron infusion and I ask if they’d have the infusion again, they typically say that they would because they recognise the benefits,” he says.

Although testing iron levels has been routine for many years, correcting iron deficiency has become much more of a focus. Low iron levels were once tested merely to detect sub-optimally controlled disease, and it was difficult to sufficiently replenish iron stores. These days, clinicians are more actively trying to correct iron deficiency when it’s detected, says Professor Gibson. “It’s very good to see that iron deficiency is becoming a greater focus for clinicians, and patients will thank us for it,” he says.

Despite the ease of correcting iron deficiency since the introduction of high-dose iron infusions, Professor Gibson warns against complacency when managing patients who again present with low iron after having already received an iron infusion. “We should question whether we’re adequately treating the disease if a patient requires ongoing iron infusions,” he explains. He says that recurrent low iron levels may indicate ongoing inflammation and disease activity.

Iron deficiency is common in IBD

Iron deficiency is considered to be the most common nutritional problem in IBD, and iron deficiency anaemia is estimated to occur in around a third of patients, significantly impacting quality of life.¹

Factors causing anaemia in IBD include insufficient dietary intake or absorption, chronic blood loss, and the impact of the hepcidin response due to chronic inflammation. The hepicidin-mediated block is commonly recognised to inhibit oral iron absorption, rendering oral iron supplements largely ineffective.¹

The hepcidin response is also understood to inhibit mobilisation of iron stores, but high-dose intravenous iron overcomes this block, allowing the successful treatment of anaemia of chronic disease.¹

Apart from considerations related to the hepcidin response, there are a number of other reasons why oral iron therapy may not be an appropriate choice for IBD patients, says Professor Gibson. “I would not recommend oral iron therapy for patients with inflammatory bowel disease,” he says, and lists issues with oral iron supplements, including poor tolerability, time (usually months) to adequately replenish iron stores, irritation to the gut, and poor adherence.

Don’t wait for iron deficiency anaemia

Professor Gibson believes that focus should be on correcting iron deficiency, as opposed to treating iron deficiency anaemia. A serum ferritin level below 30 µg/L for an adult is diagnostic for iron deficiency (anaemia is diagnosed when the haemoglobin level is below the normal reference range for the laboratory performing the test).²

‘Focusing on iron deficiency anaemia seems to miss the point when we can correct the underlying micronutrient deficiency’, says Professor Gibson. He adds that iron is involved in multiple metabolic pathways, so correcting any deficiency will possibly have other benefits for the patient, in addition to treating or preventing anaemia.

High-dose iron needs in IBD

International guidelines suggest that anaemic patients will rarely have an iron deficit of less than 1,000mg.³ Except for patients with a lower body weight (50 – 70 kg) and a haemoglobin level above 100 g/L, most patients with iron deficiency will need a dose of iron between 1,500 mg and 2,000 mg.⁴

An analysis of seven clinical studies examining the benefits of higher doses⁵ found that cumulative doses of 1,000mg were insufficient in the majority of anaemic patients and that doses around 1,500mg were closer to the iron deficit in these patients.

An observational study⁶ looking at treatment efficacy, dosing needs and prescribing practices in 282 iron deficient patients (with Crohn’s disease, ulcerative colitis, chronic blood loss, malabsorption or malignancy) found that the mean calculated total iron need was 1,481 mg. However, patients typically received lower doses than the calculated total iron need, which had implications for effectiveness.

Overall, response following the first treatment was achieved in 75% of patients who were anaemic at baseline.⁶ Response rates after first treatment increased with increasing doses: response rates ranged from 57% for doses below 1,000 mg, to 73% for doses of 1,000 mg, to 86% for doses above 1,000 mg. These were found to be statistically significant increases, even when correcting for baseline haemoglobin (p<0.05).⁶

The results showed that those who received an iron dose above 1,000 mg had a 65% lower probability of needing retreatment compared with those given 1,000 mg. “A high dose, especially over 1,000 mg, reduced the need for retreatment. The administration of higher doses, as recommended in current guidelines, seems required for full iron correction and prevention of iron deficiency anaemia,” the authors conclude.⁶

The convenience of high-dose iron infusions

Although most high-dose iron therapies have a ceiling dose of 1,000 mg, the formulation of ferric derisomaltose (Monofer) allows for it to be given in single doses of up to 20mg/kg to a maximum of 1,500 mg over 30 minutes or more.⁴ This is the result of the controlled slow release of iron, which is tightly bound to the carbohydrate in a matrix structure, limiting the potential for toxicity.⁶

The higher dosing range for ferric derisomaltose may be useful in patients with IBD, since those requiring doses above 1,000 mg (and below 1,500 mg) can receive their full iron requirement in a single clinic visit. It’s been suggested that the convenience of reduced clinic visits will result in improved patient compliance, reduced patient costs associated with clinic attendance, and reduced healthcare costs associated with nursing time and patient throughput.¹

Iron deficiency has a clear impact on quality of life

A recent observational study⁷ found a 37% prevalence of iron deficiency without anaemia in patients with inflammatory bowel disease, with female gender and the presence of inflammatory activity associated with its occurrence. Patients with iron deficiency without anaemia had lower overall quality of life scores and there was an increase in the presence of extreme fatigue of around 30% in these patients. The authors concluded that iron deficiency, “has a clear negative impact on HRQoL.” They suggested, “A more active approach is needed to treat this complication.”

References

1. Gozzard D. When is high-dose intravenous iron repletion needed: Assessing new treatment options. Drug Des Devel Ther 2011;5:51-60 https://www.ncbi.nlm.nih.gov/pubmed/21340038
2. Red Cross Blood Service 2017, Diagnosis and investigation of iron deficiency anaemia, Red Cross Blood Service, viewed 8^th May, 2019, <https://transfusion.com.au/transfusion_practice/anaemia_management/iron_deficiency_anaemia/diagnosis_and_investigation>
3. Gasche C, et al. 2007 Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis. 2007 Dec;13(12):1545–53. https://www.ncbi.nlm.nih.gov/pubmed/17985376
4. Monofer Australian Product Information https://www.tga.gov.au/sites/default/files/auspar-ferric_derisomaltose-181105-pi.pdf
5. Koch TA, et al. Intravenous iron therapy inpatients with iron deficiency anemia: Dosing considerations. Anemia. 2015;2015:763576. https://www.ncbi.nlm.nih.gov/pubmed/26257955
6. Frigstad SO, et al. The NIMO Scandinavian Study: A prospective observational study or iron isomaltoside treatment in patients with iron deficiency. Gastroenterol Res Pract. 2017;2017:4585164. doi: 10.1155/2017/4585164. https://www.ncbi.nlm.nih.gov/pubmed/29213281/
7. Gonzalez Alayon C, et al. Prevalence of iron deficiency without anaemia in inflammatory bowel disease and impact on health-related quality of life. Gastroenterol Hepatol. 2018 Jan;41(1):22–29. https://www.ncbi.nlm.nih.gov/pubmed/28899570