Rusfertide for iron overload in haemochromatosis

We read with great interest the phase 2, single-arm study on the use of rusfertide in haemochromatosis by Kris V Kowdley and colleagues. 1 Kowdley KV Modi NB Peltekian K et al. Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trial. Lancet Gastroenterol Hepatol. 2023; 8: 1118-1128 Summary Full Text Full Text PDF Scopus (1) Google Scholar Most society guidelines, including the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases, recommend serum ferritin and not transferrin saturation for deciding the need and timing of phlebotomy in haemochromatosis. 2 Zoller H Schaefer B Vanclooster A et al. EASL Clinical Practice Guidelines on haemochromatosis. J Hepatol. 2023; 791341 Google Scholar , 3 Bacon BR Adams PC Kowdley KV Powell LW Tavill AS Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011; 54: 328-343 Crossref PubMed Scopus (491) Google Scholar The recruited patients were already on maintenance phlebotomies, and it is reasonable to presume that the frequency of phlebotomies (before the trial) were largely dictated by ferritin levels in accordance with current practice guidelines. After initiation of rusfertide, the decision to assess the need for phlebotomy based on the serum ferritin and transferrin saturation values in comparison to the pre-phlebotomy parameters is akin to a shifting of goalposts and in our opinion is a major confounder in comparing the frequency of phlebotomies on rusfertide with the baseline frequency in the previous 24 weeks. It also complicates the assessment of other outcomes such as independence from phlebotomy and time to first phlebotomy. Indeed, a randomised controlled trial is needed to truly answer these questions. The mechanism and clinical significance of the paradoxical rise in ferritin with rusfertide also needs granular evaluation. Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trialRusfertide prevents iron re-accumulation in the absence of phlebotomies and could be a viable therapeutic option for selected patients with haemochromatosis. Full-Text PDF Rusfertide for iron overload in haemochromatosis – Authors' replyWe thank Muhammad Uwais Ashraf and colleagues for their interest in our single-arm phase 2 study on the use of rusfertide in haemochromatosis.1 While the average number of phlebotomies was 2·31 across 24 weeks, seven (44%) of 16 patients received three to four phlebotomies across 24 weeks. Full-Text PDF