According to a randomized European trial, modern intravenous iron replacement therapy resulted in a much higher incidence of hypophosphatemia in patients with anemia associated with inflammatory bowel disease (IBD), despite a comparable effect on hemoglobin and iron stores.
Heinz Zoller, MD, reports that in the PHOSPHARE-IBD study of 97 IBD patients with iron deficiency anemia scheduled for iron carboxymaltose (FCM; Injectafer) versus iron demethylmaltose (FDI; Monoferric). higher in patients. , Medical University of Innsbruck, Austria, and colleagues.
From baseline to day 35, 51% of FCM patients and 8.3% of FDI patients had hypophosphatemia at any time, as evidenced by serum phosphate levels less than 2.0 mg/dL (adjusted risk difference – 42.8, 95% CI -57.1 to -24.6). , P<0,0001), — написала группа в Gut. , P<0.0001), the group wrote in Gut.
The researchers used the same doses based on hemoglobin and body weight for both products to rule out possible confounding factors in previous trials. The highest incidence of hypophosphatemia occurred within the first 2 weeks of infusion, and remained elevated in the FCM group at 70 days (59.2% vs 12.5%, P<0.0001). The highest incidence of hypophosphatemia occurred within the first 2 weeks of infusion, and remained elevated in the FCM group at 70 days (59.2% vs 12.5%, P<0.0001). Самая высокая частота гипофосфатемии возникла в течение первых 2 недель инфузии и оставалась повышенной в группе FCM через 70 дней (59,2% против 12,5%, P<0,0001). The highest incidence of hypophosphatemia occurred during the first 2 weeks of infusion and remained elevated in the FCM group after 70 days (59.2% vs 12.5%, P<0.0001).低磷血症的最高发生率发生在输注的前2 周内，并且在FCM 组在70 天时仍然升高（59.2% vs 12.5%，P<0.0001）。低磷血症的最高发生率发生在输注的前2 周内，并且在FCM 组在70 天时仍然升高（59.2% vs 12.5%，P<0.000 Самая высокая частота гипофосфатемии возникла в течение первых 2 недель инфузии и оставалась повышенной в течение 70 дней в группе FCM (59,2% против 12,5%, P<0,0001). The highest incidence of hypophosphatemia occurred during the first 2 weeks of infusion and remained elevated for 70 days in the FCM group (59.2% vs 12.5%, P<0.0001).
“Despite the same efficacy and no differences in allergic reactions, the two most commonly used modern intravenous iron preparations in Europe have a clear safety profile, as desmethylmaltose iron can be considered a safer preparation,” Zoller told MedPage Today.
Iron deficiency anemia is a common extraintestinal complication of IBD that can impair physical and cognitive function and increase the risk of hospitalization. As mentioned earlier, FCM and FDI showed comparable efficacy in correcting iron deficiency anemia with almost the same increase in hemoglobin after 70 days (25.2 and 24.9 g/l, respectively).
Differences in the incidence of hypophosphatemia between the two iron replacement drugs observed in the past were partly explained by the severity or etiology of iron deficiency, the underlying renal function of the patients, and different dosing regimens for intravenous drugs. . A previous randomized trial comparing two iron replacement therapies, the US PHOSPHARE-IDA trial, also showed a higher incidence of hypophosphatemia in FCM, although dosage and dosing schedules varied according to the relevant FDA-approved prescribing information.
“The current study also showed that, despite recovery from hypophosphatemia, the course of a cascade of biochemical changes associated with high expression of FGF23 [fibroblast growth factor 23], called “6H syndrome”, is independent of patients receiving FCM,” Zoller. and colleagues wrote.
“In particular, bone-specific [alkaline phosphatase] remained elevated in the FCM group compared to the FDI group at day 70, meaning that FCM affected bone turnover throughout the trial and beyond,” they continued. “This finding may link hypophosphatemia to osteomalacia, a growing complication of FCM that was recently listed as a special warning in the European information for patients with FCM.”
Zoller told MedPage Today that further research “is focused on understanding why the two drugs differ in their induction of FGF23, a hormone that causes a complex response leading to hypophosphatemia, to avoid future drug development.” To have this side effect and understand this dysregulation.” .”
PHOSPHARE-IBD is a double-blind, randomized trial of 97 IBD patients – 61% with ulcerative colitis (UC) and 39% with Crohn’s disease (CD) – in 20 European hospitals since 2018. 2020.
Eligible patients required a serum ferritin level of 100 ng/mL or lower, a hemoglobin level of less than 130 g/L, and required rapid iron supplementation or had oral iron intolerance/insensitivity, among other criteria.
Participants were randomized in a 1:1 ratio to receive the same dose of FDI or FCM based on hemoglobin and body weight at baseline and 35 days later. For patients with hemoglobin levels below 100 g / l, the total dose is 1500 mg for patients weighing less than 70 kg and 2000 mg for patients weighing 70 kg or more. Patients with a hemoglobin level of 100 g/l and above received a total dose of 1500 mg.
Zoller and colleagues wrote: “Given the design of the study, it can be concluded that the observed differences in the incidence of hypophosphatemia are entirely due to differences in iron preparations, and not to the total dose of iron, dosing regimen, differences in CD compared with UC. or other patient-related factors such as kidney function, severity of inflammation, degree of iron deficiency, or vitamin D deficiency.”
The median age of patients in the study was 42 years, 53% were women, the majority were white (86%), and the mean body mass index was 27.6. The mean hemoglobin level at baseline was 105 g/l.
The frequency of adverse events (AEs) and serious adverse events (AEs) was similar for different products, but most of them were mild (80-83%). The FCM group had more vitamin D deficiency (35% vs 23%) and more cases of nasopharyngitis (20% vs 17%) than the FDI group. In the FDI group, headache (19% vs. 10%) was more common, as was nausea (13% vs. 2%). More patients in the FDI group discontinued treatment due to AEs (6% vs 2%).
Although both interventions resulted in improvement in patient-reported fatigue scores, larger and faster improvements were seen in the FDI group, although this difference lost significance after 70 days.
Data limitations include short follow-up time and inability to fully evaluate clinical outcomes.
Zaina Hamza is MedPage Today’s staff writer for gastroenterology and infectious diseases. She is based in Chicago.
Zoller announced funding from Abbvie, Bayer, Falk, Gilead, Merz, Medice, Pierre Fabre, Pharmacosmos, Sanofi and Vifor. The co-authors report relationships with several pharmaceutical and industrial companies. The co-author also reported co-authors of patents related to parenteral iron preparations.
LINK TO SOURCE: Zoller H et al. “Hypophosphatemia after administration of iron desferiomaltose and iron carboxymaltose in patients with iron deficiency anemia due to inflammatory bowel disease (Phosphare-IBD): a randomized clinical trial” Gut 2022; DOI: 10.1136/gutjnl-2022-327897.
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Post time: Sep-23-2022