Objective To evaluate the efficacy, safety, and economy of 4 intravenous iron formulations in the treatment of iron deficiency anemia (IDA) by rapid health technology assessment, and to provide evidence for clinical decision-making.
Methods PubMed, Embase, the Cochrane Library, CNKI, WanFang, SinoMed, and official websites of international health technology assessment agencies were electronically searched to collect health technology assessment reports, systematic reviews/Meta-analysis, and pharmacoeconomic studies concerning the treatment of IDA with iron sucrose (IS), iron dextran (ID), ferric carboxymaltose (FCM), and iron isomaltoside (IIM) from the inception to August 15, 2024. Two researchers independently screened the studies, extracted data and assessed the quality of included studies. The results were then qualitatively described and analyzed.
Results A total of 32 studies were included, including one health technology assessment report, 16 systematic reviews/Meta-analysis, and 15 pharmacoeconomic evaluations. In terms of effectiveness, FCM had a higher response rate than that of IS (P﹤0.05), FCM and IIM had no statistical difference (P >0.05). Regarding hemoglobin level change, patients treated with FCM had higher hemoglobin levels than those treated with IS (P﹤0.05); the improvement in hemoglobin levels between IIM and FCM was inconclusive. In terms of ferritin level change, FCM might be superior to the other three intravenous iron formulations. In terms of safety, the adverse event rates for FCM, IS, ID and IIM were 12.0%, 15.3%, 12.0% and 17.0%, respectively; IIM was significantly associated with a lower rate of cardiovascular adverse events compared to FCM and IS (P﹤0.05); FCM had the highest rate of hypophosphatemia among the four formulations (P﹤0.05), and there was no significant difference among IIM, IS and ID (P>0.05); IIM had a lower risk of severe or serious hypersensitivity reactions compared to FCM and IS. In terms of economy, FCM and IIM had an economic advantage compared to IS. The economic efficiency ranking among IS, ID, and FCM was in the order of FCM, ID, and IS, the economic comparison between FCM and IIM remains inconclusive and needs to be further demonstrated.
Conclusion FCM and IIM have good efficacy, safety and economy in the treatment of IDA, but most of the included economy studies based on foreign populations, and domestic economic studies need to be further demonstrated.
1. GBD 2021 Anaemia Collaborators. Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the global burden of disease study 2021[J]. Lancet Haematol, 2023, 10(9): e713-e734. DOI: 10.1016/S2352-3026(23)00160-6.
2. Aleem A, Alsayegh F, Keshav S, et al. Consensus statement by an expert panel on the diagnosis and management of iron deficiency anemia in the Gulf Cooperation Council countries[J]. Med Princ Pract, 2020, 29(4): 371-381. DOI: 10.1159/000503707.
3. Api O, Breyman C, Çetiner M, et al. Diagnosis and treatment of iron deficiency anemia during pregnancy and the postpartum period: iron deficiency anemia working group consensus report[J]. Turk J Obstet Gynecol, 2015, 12(3): 173-181. DOI: 10.4274/tjod.01700.
4. Numan S, Kaluza K. Systematic review of guidelines for the diagnosis and treatment of iron deficiency anemia using intravenous iron across multiple indications[J]. Curr Med Res Opin, 2020, 36(11): 1769-1782. DOI: 10.1080/03007995. 2020.1824898.
5. 中华医学会血液学分会红细胞疾病(贫血)学组. 铁缺乏症和缺铁性贫血诊治和预防的多学科专家共识(2022年版)[J]. 中华医学杂志, 2022, 102(41): 3246-3256. DOI: 10.3760/cma.j.cn112137-20220621-01361.
6. 廖敏婧, 张连生. 铁缺乏及缺铁性贫血规范化诊治[J]. 中华内科杂志, 2023, 62(6): 722-727. [Liao MJ, Zhang LS. Standardized diagnosis and treatment of iron deficiency and iron-deficiency anemia[J]. Chinese Journal of Internal Medicine, 2023, 62(6): 722-727.] DOI: 10.3760/cma.j.cn112138-20230210-00074.
7. 刘立民, 吴德沛. 大剂量静脉铁剂治疗缺铁性贫血的应用进展[J]. 中华血液学杂志, 2022, 43(11): 960-963. [Liu LM, Wu DP. Application progress of high-dose intravenous iron in the treatment of iron deficiency anemia[J]. Chinese Journal of Hematology, 2022, 43(11): 960-963.] DOI: 10.3760/cma.j.issn.0253-2727.2022.11.014.
8. 中华医学会血液学分会红细胞疾病(贫血)学组. 静脉铁剂应用中国专家共识(2019年版)[J]. 中华血液学杂志, 2019, 40(5): 358-362. DOI: 10.3760/cma.j.issn.0253-2727.2019.05.002.
9. Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults[J]. Gut, 2021, 70(11): 2030-2051. DOI: 10.1136/gutjnl-2021-325210.
10. 杨欣, 李艺, 狄文, 等. 妇科围手术期患者血液管理的专家共识[J]. 中国妇产科临床杂志, 2019, 20(6): 560-563. DOI: 10.13390/j.issn.1672-1861.2019.06.027.
11. 中华医学会外科学分会, 中华外科杂志编辑委员会. 普通外科围手术期缺铁性贫血管理多学科专家共识[J]. 中华外科杂志, 2020, 58(4): 252-256. DOI: 10.3760/cma.j.cn112139-20200210-00073.
12. 中华医学会围产医学分会. 妊娠期铁缺乏和缺铁性贫血诊治指南[J]. 中华围产医学杂志, 2014, 17(7): 451-454. DOI: 10.3760/cma.j.issn.1007-9408.2014.07.006.
13. Centre for Perioperative Care. Guideline for the management of anaemia in the perioperative pathway [EB/OL]. (2022-09) [2024-03-02]. https://cpoc.org.uk/sites/cpoc/files/documents/2022-09/1.%20CPOC_GuidelinefortheManagementofAnaemia_September2022.pdf.
14. Mansour D, Hofmann A, Gemzell-Danielsson K. A review of clinical guidelines on the management of iron deficiency and iron-deficiency anemia in women with heavy menstrual bleeding[J]. Adv Ther, 2020, 38(1): 201-225. DOI: 10.1007/s12325-020-01564-y.
15. Auerbach M, Macdougall IC, Rodgers GM, et al. The iron revolution: keeping abreast of the developments in iron therapy[J]. Am J Hematol, 2022, 97(3): 250-252. DOI: 10.1002/ajh.26427.
16. 汤莹, 杜光, 孙秋雁. 缺铁性贫血临床药物治疗进展[J]. 中国医院药学杂志, 2022, 42(23): 2560-2566. [Tang Y, Du G, Sun YQ. Progress in clinical application of drugs to the treatment of iron deficiency anemia[J]. Chinese Journal of Hosptal Pharmacy, 2022, 42(23): 2560-2566.] DOI: 10.13286/j.1001-5213.2022.23.22.
17. INAHTA. INAHTA HTA Checklist English[EB/OL]. (2007-05) [2024-06-28]. http://www.Inahta.org/wp-content/up-loads/2014/04/INAHTA-HTA-Checklist-English.pdf.
18. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both[J]. BMJ, 2017, 358: j4008. DOI: 10.1136/bmj.j4008.
19. 姚媛, 苏芬丽, 孙旭, 等. 度拉糖肽治疗2型糖尿病的快速卫生技术评估[J]. 药物流行病学杂志, 2023, 32(8): 931-940. [Yao Y, Su FL, Sun X, et al. Rapid health technology assessment of dulaglutide for the treatment of type 2 diabetes mellitus[J]. Chinese Journal of Pharmacoepidemilolgy, 2023, 32(8): 931-940.] DOI: 10.19960/j.issn.1005-0698.202308012.
20. Husereau D, Drummond M, Augustovski F, et al. Consolidated health economic evaluation reporting standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations[J]. Value Health, 2022, 25(1): 3-9. DOI: 10.1016/j.jval.2021.11.1351.
21. 张莉, 冯钟文, 周鹏翔, 等. 替诺福韦治疗成人慢性乙型肝炎的快速卫生技术评估[J]. 临床药物治疗杂志, 2023, 32(18): 112-118. [Zhang L, Feng ZW, Zhou PX, et al. Rapid health technology assessment of tenofovir in the treatment of adult chronic hepatitis B[J]. Clinical Medication Journal, 2023, 32(18): 112-118.] DOI: 10.3969/j.issn.1006-4931.2023.18.024.
22. Aksan A, Işık K, Radeke HH, et al. Systematic review with network meta‐analysis: comparative efficacy and tolerability of different intravenous iron formulations for the treatment of iron deficiency anaemia in patients with inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2017, 45(10): 1303-1318. DOI: 10.1111/apt.14043.
23. Bellos I, Frountzas M, Pergialiotis V. Comparative risk of hypophosphatemia following the administration of intravenous iron formulations: a network meta-analysis[J]. Transfus Med Rev, 2020, 34(3): 188-194. DOI: 10.1016/j.tmrv.2020.07.002.
24. Glaspy JA, Lim-Watson MZ, Libre MA, et al. Hypophosphatemia associated with intravenous iron therapies for iron deficiency anemia: a systematic literature review[J]. Ther Clin Risk Manag, 2020, 16: 245-259. DOI: 10.2147/TCRM.S243462.
25. Gordon M, Sinopoulou V, Iheozor-Ejiofor Z, et al. Interventions for treating iron deficiency anaemia in inflammatory bowel disease[J]. Cochrane Database Syst Rev, 2021, 2021(1): 1-90. DOI: 10.1002/14651858.CD013529.pub2.
26. Kennedy NA, Achebe MM, Biggar P, et al. A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose[J]. Int J Clin Pharm, 2023, 45(3): 604-612. DOI: 10.1007/s11096-023-01548-2.
27. Moore RA, Gaskell H, Rose P, et al. Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (ferinject) from clinical trial reports and published trial data[J]. BMC Blood Disord, 2011, 11(1): 1-13. DOI: 10.1186/1471-2326-11-4.
28. Pollock RF, Biggar P. Indirect methods of comparison of the safety of ferric derisomaltose, iron sucrose and ferric carboxymaltose in the treatment of iron deficiency anemia[J]. Expert Rev Hematol, 2020, 13(2): 187-195. DOI: 10.1080/17474086.2020.1709437.
29. Pollock RF, Kalra PA, Kalra PR, et al. A systematic review, meta-analysis, and indirect comparison of blindly adjudicated cardiovascular event incidence with ferric derisomaltose, ferric carboxymaltose, and iron sucrose[J]. Adv Ther, 2022, 39(10): 4678-4691. DOI: 10.1007/s12325-022-02242-x.
30. Pollock RF, Muduma G. A systematic literature review and indirect comparison of iron isomaltoside and ferric carboxymaltose in iron deficiency anemia after failure or intolerance of oral iron treatment[J]. Expert Rev Hematol, 2019, 12(2): 129-136. DOI: 10.1080/17474086. 2019.1575202.
31. Qassim A, Mol BW, Grivell RM, et al. Safety and efficacy of intravenous iron polymaltose, iron sucrose and ferric carboxymaltose in pregnancy: a systematic review[J]. Aust N Z J Obstet Gynaecol, 2018, 58(1): 22-39. DOI: 10.1111/ajo.12695.
32. Rogozińska E, Daru J, Nicolaides M, et al. Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (frida): a systematic review and network meta-analysis[J]. Lancet Haematol, 2021, 8(7): e503-e512. DOI: 10.1016/S2352-3026(21)00137-X.
33. Schaefer B, Tobiasch M, Viveiros A, et al. Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside--a systematic review and meta‐analysis[J]. Br J Clin Pharmacol, 2021, 87(5): 2256-2273. DOI: 10.1111/bcp.14643.
34. Shin HW, Go DY, Lee SW, et al. Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for iron deficiency anemia in obstetric and gynecologic patients[J]. Medicine (Baltimore), 2021, 100(20): 1-10. DOI: 10.1097/MD.0000000000024571.
35. 黄媛, 苏娜, 李丹, 等. 不同静脉铁剂治疗贫血效果的网状meta分析[J]. 临床药物治疗杂志, 2022, 20(12): 29-34. [Huang Y, Su N, Li D, et al. Network meta-analysis of different intravenous irons in the treatment of anemia[J]. Clinical Medication Journal, 2022, 20(12): 29-34.] DOI: 10.3969/j.issn.1672-3384.2022.12.006.
36. Singh Y, Bharadwaj MK, Patrikar S. Comparative analysis of injection ferric carboxymaltose vs iron sucrose for treatment of iron-deficiency anemia in pregnancy: systematic review and meta-analysis[J]. J SAFOG, 2023, 15(5): 629-36. DOI: 10.5005/jp-journals-10006-2311.
37. Joshi B, Srimathi G, Revathy R, et al. Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: a systematic review and meta-analysis[J]. Indian J Med Res, 2024, 159(1). DOI: 10.4103/ijmr.ijmr_246_23.
38. Aksan A, Beales ILP, Baxter G, et al. Evaluation of the cost-effectiveness of iron formulations for the treatment of iron deficiency anaemia in patients with inflammatory bowel disease in the UK[J]. Clinicoecon Outcomes Res, 2021, 13: 541-552. DOI: 10.2147/CEOR.S306823.
39. Aksan A, Schoepfer A, Juillerat P, et al. Iron formulations for the treatment of iron deficiency anemia in patients with inflammatory bowel disease: a cost-effectiveness analysis in Switzerland[J]. Adv Ther, 2021, 38(1): 660-677. DOI: 10.1007/s12325-020-01553-1.
40. Argüelles-Arias F, Bermejo F, Borrás-Blasco J, et al. Cost-effectiveness analysis of ferric carboxymaltose versus iron sucrose for the treatment of iron deficiency anemia in patients with inflammatory bowel disease in Spain[J]. Therap Adv Gastroenterol, 2022, 15: 1-12. DOI: 10.1177/17562848221086131.
41. Bager P, Dahlerup JF. The health care cost of intravenous iron treatment in ibd patients depends on the economic evaluation perspective[J]. J Crohns Colitis, 2010, 4(4): 427-430. DOI: 10.1016/j.crohns.2010.01.007.
42. Basha A, Ibrahim MIM, Hamad A, et al. Efficacy and cost effectiveness of intravenous ferric carboxymaltose versus iron sucrose in adult patients with iron deficiency anaemia[J]. PLoS One, 2021, 16(8): 1-13. DOI: 10.1371/journal.pone.0255104.
43. Bhandari S. Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice[J]. Ther Clin Risk Manag, 2011, 7: 501-509. DOI: 10.2147/TCRM.S25882.
44. Calvet X, Gené E, Àngelruíz M, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose or oral iron as preoperative treatment in patients with colon cancer and iron deficiency anaemia[J]. Technol Health Care, 2016, 24(1): 111-120. DOI: 10.3233/THC-151074.
45. Calvet X, Ruíz MÀ, Dosal A, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency[J]. PLoS One, 2012, 7(9): 1-5. DOI: 10.1371/journal.pone.0045604.
46. Fragoulakis V, Kourlaba G, Goumenos D, et al. Economic evaluation of intravenous iron treatments in the management of anemia patients in Greece[J]. Clinicoecon Outcomes Res, 2012, 4: 127-134. DOI: 10.2147/CEOR.S30514.
47. Hu S, Liu L, Pollock RF, et al. Intravenous iron for the treatment of iron deficiency anemia in China: a patient-level simulation model and cost-utility analysis comparing ferric derisomaltose with iron sucrose[J]. J Med Econ, 2022, 25(1): 561-570. DOI: 10.1080/13696998.2022.2065092.
48. Pollock RF, Muduma G. A patient-level cost-effectiveness analysis of iron isomaltoside versus ferric carboxymaltose for the treatment of iron deficiency anemia in the United Kingdom[J]. J Med Econ, 2020, 23(7): 751-759. DOI: 10.1080/13696998.2020.1745535.
49. Szucs TD, Blank PR, Schwenkglenks M, et al. Potential health economic impact of intravenous iron supplementation to erythropoiesis-stimulating agent treatment in patients with cancer- or chemotherapy-induced anemia[J]. Oncology, 2011, 81(1): 45-49. DOI: 10.1159/000330738.
50. Aladham L, Benmouhoub N, Bradai M, et al. Cost-minimization analysis in iron-deficiency anemia comparing intravenous ferric carboxymaltose to standard of care in pregnant women in Algeria[J]. J App Hematol, 2023, 14(4): 281-6. DOI: 10.4103/joah.joah_64_23.
51. Iqbal TH, Kennedy N, Dhar A, et al. Cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anemia in England[J]. J Med Econ, 2024, 27(1): 392-403. DOI: 10.1080/13696998.2024.2313932.
52. 孙文韬, 庄铃香, 马爱霞. 羧基麦芽糖铁治疗中国缺铁性贫血成人患者的成本-效果分析[J]. 中国药房, 2023, 34(22): 2750-2755. [Sun WT, Zhuang LX, Ma AX, et al. Cost-effectiveness analysis of ferric carboxymaltose for treating iron deficiency anemia in adult Chinese patients[J]. China Pharmacy, 2023, 34(22): 2750-2755.] DOI: 10.6039/j.issn.1001-0408.2023.22.11.
53. CADTH. Cadth C, Iron (Ⅲ) isomaltoside 1000 [EB/OL].(2015-05-19) [2024-02-02]. https://www.cadth.ca/iron-iii-isomaltoside-1000.
54. Evstatiev R, Marteau P, Iqbal T, et al. Fergicor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease[J]. Gastroenterology, 2011, 141(3): 846-853. DOI: 10.1053/j.gastro.2011.06.005.