The Significance of Hypophosphatemia in Deciding on an Optimal Clinical Choice of Parenteral Iron Therapy in Patients with Chronic Inflammatory Bowel Disease in Slovenia: An Umbrella Review and Economic Evaluation

<b>Background/Objectives</b>: Iron-deficiency anemia (IDA) is a common extraintestinal complication of inflammatory bowel disease (IBD). Among high-dose intravenous (IV) iron options, ferric carboxymaltose (FCM) carries a higher risk of treatment-emergent hypophosphatemia than ferric derisomaltose (FDI), with potential clinical consequences. Slovenia's healthcare setting, characterized by very low IV iron infusion tariffs and recent pricing in which FCM is substantially less expensive than FDI, warrants a setting-specific cost effectiveness evaluation. <b>Methods</b>: We integrated two methodological components: (i) a payer-perspective cost-effectiveness analysis using a patient-level microsimulation model with (ii) an umbrella review of systematic reviews and a targeted search of expert consensus statements on IV-iron-associated hypophosphatemia. <b>Results</b>: In the base case, FDI required fewer infusions than FCM (11.1 vs. 14.2 over 10 years) but generated only €95 in IV iron administration savings due to low tariffs, while drug procurement was €1166 higher with FDI than FCM. When incorporating the clinical impact of hypophosphatemia, incremental quality-adjusted life years (QALYs) were 0.136, yielding an incremental cost-effectiveness ratio (ICER) of €6590/QALY. The umbrella review consistently showed higher hypophosphatemia incidence with FCM (up to 92%) compared with other IV iron formulations (<10%), with recent recommendations emphasizing phosphate monitoring and risk mitigation through alternative formulations. <b>Conclusions</b>: Despite Slovenia's low IV iron infusion tariffs and lower FCM price, FDI remained cost-effective in this model, largely due to its more favorable hypophosphatemia profile within the model. These findings suggest that hypophosphatemia risk should be considered when selecting IV iron therapy in routine IBD care.