Ironing Out the Efficacy and Safety Profile of Ferric Carboxymaltose Infusions for the Treatment of Iron Deficiency and Iron-Deficiency Anemia in Pediatric Inflammatory Bowel Disease

Background:
Anemia is frequently observed in inflammatory bowel disease (IBD), with a higher prevalence in children (16%–72%) compared to adults (4%–67%). Oral iron treatment is associated with poor tolerance leading to low compliance and reduced effectiveness in patients with active disease due to poor absorption, iron sequestration, and greater gastrointestinal intolerance. As a result, intravenous iron therapy is typically preferred. Ferric carboxymaltose (FCM) is an intravenous iron formulation that allows for larger doses to be administered in a single session, reducing treatment frequency and potentially improving patient compliance. Despite this, there is, however, limited data on the efficacy and safety of FCM infusions in pediatric IBD patients. Existing evidence consists mainly of small retrospective and prospective studies. We present here the largest retrospective study evaluating the efficacy and safety of FCM in pediatric IBD.
Methods:
Medical records of pediatric IBD patients who had received at least 1 FCM infusion in the outpatient setting between November 2017 and February 2020 at our tertiary care institution were analyzed. Patients were excluded if they had received blood transfusions or another intravenous iron formulation within 4 weeks prior to the FCM infusion or if they were taking concomitant oral iron. Data collected included baseline disease characteristics and clinical disease activity (Physician Global Assessment [PGA]), and biochemical profiles at baseline, 1-3 months, and 12 ± 3 months after the last FCM infusion. Efficacy endpoints included normalization of hemoglobin (Hb) levels or an increase of more than 2 g/dL from baseline, and ferritin levels of ≥30 ng/mL for inactive disease or ≥100 ng/mL for active disease by 12 weeks after the end of iron replacement. Adverse events related to FCM infusions were reviewed.
Results:
This retrospective analysis included 348 patients (median age 14.3 years), with 67% (n=234) diagnosed with Crohn’s disease and 33% (n=114) with ulcerative colitis or indeterminate IBD. Half of the patients (N = 177) had quiescent disease, while the other half had active disease ranging from mild to severe (N=171). For patients with quiescent disease, median Hb levels increased from 11.5 (IQR 1.7) to 13.05 (IQR 1.3) and median ferritin levels improved from 9.75 (IQR 8.6) to 126 (IQR 105.4), [P < 0.0001]. In patients with active disease, median Hb levels also rose from 10.7 (IQR 1.9) to 12.6 (IQR 1.5) and median ferritin levels improved from 15 (IQR 23.9) to 92.4 (IQR 125.3), [P < 0.0001]. These improvements were sustained at the 12-months post infusion. Three patients experienced infusion-related reactions, requiring pharmacologic intervention.
Conclusions:
FCM infusions appear to be a safe, effective and well-tolerated treatment option for iron deficiency and iron-deficiency anemia in pediatric patients with IBD, leading to significant improvements in Hb and ferritin levels. The incidence of adverse events was low, indicating a favorable safety profile. Ongoing statistical analysis and evaluation of hypophosphatemia risk are in progress. Further pediatric prospective studies including randomized controlled trials are warranted to confirm these results and optimize treatment protocols.