Authors' objectives: To compare the effectiveness, safety, cost-effectiveness, and organisational issues of IVI preparations that are available in the Malaysian market with oral iron or other alternatives in the treatment of adult patients with iron deficiency anaemia (IDA).

Authors' results and conclusions: Efficacy/ effectiveness: Limited fair to good level of retrievable evidence has shown significant improvement in haemoglobin (Hb) concentration with preoperative IVI as well as in pregnant and postpartum women when compared to oral iron. This effect, however, was not seen in other populations included in the review, as IVI did not demonstrate any apparent benefit over the control group. In trials that compared IVI to no iron therapy, there was no strong evidence to support that preoperative IVI has led to significant improvement in Hb concentration. Only one study included in this review investigated the postoperative effect of IVI and found that it has shown favourable results on day 14 of operation compared to no iron therapy. In all studies with positive results for perioperative IVI over the control group, IVI was administered at least 14 days prior to surgery, or improvement in Hb level measured 14 days after the first dose of IVI administration. There is also a lack of head-head trial comparing different types of IVI formulations. In one study, both intravenous ferric carboxymaltose (IV FCM) and intravenous iron sucrose (IV IS) markedly improved preoperative Hb concentration, with IV FCM achieving Hb correction about three days earlier than IV IS. However, no significant difference was observed between these two formulations. The impact of IVI on blood transfusion requirement among surgical patients and other populations cannot be established due to mixed results obtained from the included studies. Almost all studies that reported on serum ferritin level showed that IVI did significantly increase the mean ferritin level compared to the control group with oral iron or no iron therapy. There were mixed results for mean transferrin saturation level as some studies reported significant increased compared to control, while a few reported comparable effects were observed between groups. Safety: There was a substantial good level of retrievable evidence to suggest that the use of IVI is safe with no significant differences in mortality and severe adverse reactions/ events within the follow-up period were observed between IVI and control group. Similarly, infection rates were comparable among groups except for nondialysis CKD patients treated with IVI documented a higher incidence of hospitalised heart failure and significant lung and skin infection rates. IVI was also associated with decreased risk for gastrointestinal adverse events, particularly with IV IS, intravenous iron dextran (IV ID) and IV FCM, and when compared to oral iron or no iron therapy. On the other hand, the risk for neurologic and muscle and skeletal adverse events increased with IVI, particularly with IV IS and IV FCM, respectively. While there was no significant difference in risk for hypersensitivity reaction between IV FCM and IV IS, the odds of experiencing severe hypersensitivity reaction with intravenous iron derisomaltose (IV IIM) was 59% lower than that of IV FCM, and 49% lower than that of IV IS. The risk for cardiovascular adverse event was reported to comparable between IV FCM and IV IS. However, this risk was noted to be lower with IV FCM, while the use of intravenous ferric gluconate (IV FG) was associated with increased risk. There was also a risk for IVI-related infusion reaction, with increased risk for such reaction was observed for IV IS and IV FCM with more serious infusion reactions were seen with IV FG. Additionally, hypophosphataemia was one the common electrolytes imbalance documented with IVI therapy. Organisational: There was a limited fair to good level of retrievable evidence to suggest that treatment of IDA with IVI resulted in no significant difference in length of hospitalisation between IVI and control groups, be it in perioperative settings, critical care patients or pregnant women. Economic implication: Theoretical simulation comparing preoperative optimisation of Hb with IVI to oral iron in patients with primary knee arthroplasty has shown that IVI resulted in cost savings of €831 and €405 for blood transfusion avoided per patient and each RBC unit spared, respectively. Similarly, preoperative treatment with IVI in patients undergoing abdominal surgery has resulted in cost savings of €786 per case by reducing the blood transfusion rate and costs paid by hospitals for extended hospitalisation when compared with standard medical therapy. From these studies, factors that highly influenced the resulting cost savings were the cost of the outpatient clinic, transfusion rate in all treatment arms, as well as the length of hospitalisation.

Authors' recommendations: Based on the review, IVI may be considered for expediting haemoglobin response in patients with IDA where haemorrhage is anticipated. Nevertheless, given the current available evidence, the impact of IVI on allogeneic blood transfusion requirement among IDA patients remains inconclusive.

Authors' methods: Electronic databases searched through the Ovid interface: MEDLINE® and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) 1946 to May 19, 2020; EBM Reviews - Cochrane Database of Systematic Reviews 2005 to May 14, 2020; EBM Reviews - Database of Abstracts of Reviews of Effects 1st Quarter 2016; EBM Reviews - Cochrane Central Register of Controlled Trials April 2020; EBM Reviews - Health Technology Assessment 4th Quarter 2016; EBM Reviews - NHS Economic Evaluation Database 1st Quarter 2016. Searches were also run on PubMed, the United States Food and Drug Administration (US FDA) and INAHTA databases. No limits were applied. Additional articles were identified from reviewing the references of retrieved articles. The search strategy was updated until 20th May 2020. In addition, Google was used to search for additional web-based materials and information.

Project Status: Completed

URL for project: https://www.moh.gov.my/index.php/database_stores/store_view/30?mid=609

Year Published: 2020

URL for published report: https://www.moh.gov.my/index.php/database_stores/store_view_page/30/341

Requestor: Ministry of Health

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Malaysia

Organisation Name: Malaysian Health Technology Assessment

Contact Address: Malaysian Health Technology Assessment Section, Ministry of Health Malaysia, Federal Government Administrative Centre, Level 4, Block E1, Parcel E, 62590 Putrajaya Malaysia Tel: +603 8883 1229

Contact Name: htamalaysia@moh.gov.my

Contact Email: htamalaysia@moh.gov.my

Copyright: Malaysian Health Technology Assessment Section (MaHTAS)