Safety and Efficacy of FCM in the Management of Iron Deficiency Anaemia: A Multi-Centre Cohort-Based Study

: This study investigated the efficacy and safety of ferric carboxymaltose (FCM) in the treatment of iron deficiency anaemia (IDA) in a cohort of 100 patients across four locations in West Bengal, India. The results demonstrated significant improvements in various hematological parameters, including a substantial increase in haemoglobin levels, following FCM administration. The study also highlighted the absence of adverse events, showcasing a favorable safety profile of FCM in this population. The use of FCM, a third-generation parenteral iron formulation, proved effective in addressing moderate-to-severe IDA, aligning with existing evidence supporting its efficacy and safety. The rapid and substantial improvement in haemoglobin levels observed within four weeks of FCM administration emphasizes its efficiency in iron repletion, particularly in cases where oral preparations may be insufficient. The absence of adverse effects further supports the tolerability of FCM, a crucial factor in its consideration for widespread use. The study contributes valuable real-world data, especially in the context of the high prevalence of anaemia in India. The findings underscore the potential of FCM as a cornerstone in the treatment of severe anaemia, advocating for its inclusion in targeted interventions and public health initiatives. Overall, this study adds to the growing body of evidence supporting FCM as a promising option in the management of iron deficiency anaemia.


Introduction
Anaemia stands as a pervasive global public health concern, impacting around one-third (22.8%) of the global population in the year 2019. 1 The 2019-2020 National Family Health Survey (NFHS-5) data reveals a significant prevalence of anaemia in India, where 57% of women and 25% of men between the ages of 15 and 49 exhibit this health condition. 1These statistics emphasising the urgency of targeted interventions and public health initiatives to address this critical health issue. 1 Moreover, the persistence of severe anaemia remains a significant challenge, delineated by haemoglobin (Hb) levels falling below 7 g/dL, despite the existence of Indian guidelines and dedicated efforts aimed at eradicating anaemia. 1 This underscores the need for a more targeted approach in addressing severe form of the disease. 1 Iron deficiency anaemia (IDA) stands out as the predominant cause of anaemia, with iron supplementation being the principal mode of treatment. 22] However, both oral and parenteral iron preparations have their side effects; thus, newer intravenous (IV) iron formulations with a favourable adverse events profile as compared to traditional parenteral iron products have been developed by Eskag Pharma Pvt Ltd.Ferric carboxymaltose (FCM), a third-generation parenteral iron formulation designed by Eskag Pharma Pvt Ltd could overcome the limitations of existing parenteral iron preparations.FCM, a novel non-dextran IV iron agent, had a very low immunogenic potential and thus predisposed no anaphylactic reactions to any of the participants.Its properties permitted the administration of large dosages (1000 mg/infusion) in a single session (15-minute infusion) without the necessity of a test dose.

Study design
This was a multicentre, cohort-based, observational, data collection study involving four Eskag Sanjeevani hospitals of West Bengal, India.A cohort of 100 human subjects was enrolled from four distinct centres: Basirhat (location 1), Behala (location 2), ID & BG (location 3), and Howrah (location 4).In the course of the ten-month study, commencing in June 2022 and concluding in March 2023, all participants received intravenous ferric carboxymaltose (FCM) in a diluted form (100 ml normal saline).At the commencement of the study, patient-specific information, encompassing their identities, haemoglobin levels, and batch numbers, were meticulously documented.

Patient details
Patients details along with their haemoglobin levels were recorded before administration of FCM.Other vitals, encompassing oxygen saturation, blood pressure, body temperature, pulse rate, vision, taste, anaphylactic shock, respiratory problems, and restlessness were documented as well.

Treatment characteristics
The cumulative FCM dosage for iron repletion was calculated considering both the patient's body weight and haemoglobin level.As an integral component of the standard care protocol, FCM 500/1K (manufactured by Eskag Pharma Pvt. Ltd., Kolkata, India) was administered intravenously, with each infusion not surpassing 1000 mg of iron.

Outcome Measures and Statistical Analysis
Patient data were sourced from their medical records.These records were then anonymized and meticulously documented by trained technicians using designated case record forms (CRF) tailored for the study.Additionally, the clinical opinions of physicians regarding the efficacy and safety of ferric carboxymaltose (FCM) were also recorded in the CRF.The evaluation of efficacy was conducted through a clinical assessment, considering both symptomatic and hematological improvements as documented in the medical records. 3Safety assessments were based on the scrutiny of adverse events and side effects associated with FCM, all of which were documented in the patients' medical records.

Efficacy outcomes
In the study population, noticeable improvements in various haematological parameters were observed after 4 weeks, demonstrating statistical significance (P < 0.001 for all).Specifically, haemoglobin (Hb) levels exhibited a substantial increase of 3.292 g/dL, while serum ferritin levels rose by 36.65 µg/L.Additionally, there were significant enhancements in red blood cell (RBC) count, hematocrit, mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH).Although a positive trend was noted, the increase in mean corpuscular haemoglobin concentration (MCHC) at 4 weeks compared to baseline did not reach statistical significance (P = 0.103).These findings underscore the effectiveness of the intervention in fostering improvements across a spectrum of haematological indicators, with particular emphasis on Hb levels, RBC characteristics, and iron stores.

Safety
The commonly documented adverse effects associated with ferric carboxymaltose (FCM) administration, such as nausea, headache, constipation, diarrhea, and allergic reactions, were notably absent in the present study. 4Strikingly, no adverse events, especially anaphylactic shock, were reported among the patients following FCM administration, resulting in a remarkable low rate of adverse events in the study, with 0% anaphylactic shock experienced by the patients (In the following images, value 1 depicts no adverse events).Previous studies have reported a high rate of anaphylaxis reaction after FCM injection. 5The present study proves potentiality and safety of Eskag sponsored FCM injection in this regard, with 0% rate of anaphylactic shock in the patients.This observation holds significance, particularly in the context of the study being sponsored by Eskag Pharma and involving the use of FCM injection.The absence of adverse effects underscores the potential safety profile and tolerability of FCM in the studied population.

Discussion
Expert consensus regarding the use of ferric carboxymaltose (FCM) in treating iron deficiency anaemia (IDA) underscores compelling evidence supporting both its efficacy and safety across various acute and chronic conditions.A comprehensive systematic review and network meta-analysis of 21 randomised controlled trials demonstrated significant improvements in serum ferritin levels (µg/L) with FCM compared to oral iron (∆ 172.8; 95% confidence interval [CI] 66.7-234.4).Furthermore, haemoglobin (Hb) levels (g/dL) showed significant improvement with FCM compared to intravenous ferric gluconate (∆ 0.6; 95% CI 0.2-0.9),oral iron (∆ 0.8; 95% CI 0.6-0.9),and placebo (∆ 2.1; 95% CI 1.2-3.0).Notably, FCM demonstrated a lower incidence of side effects compared to other parenteral therapies.Despite a scarcity of real-world studies on FCM, particularly from India, existing evidence suggests that haematological parameters in patients with moderate-to-severe IDA exhibit improvement within 6 to 12 weeks following intravenous (IV) iron supplementation.Oral iron supplementation, however, requires a more extended period for normalization.In contrast, Hb levels may significantly improve within two to four weeks of IV FCM supplementation, as evident in our study where Hb improvement was significant at week 4 across the entire study population, regardless of IDA severity.
A positive response to iron therapy, manifested by improved haematological parameters, serves as a reliable indicator of IDA.While Hb and ferritin are commonly used measures, their assessment can be influenced by various factors.Thus, evaluating a comprehensive array of haematological parameters provides a more thorough assessment of therapy response.In patients with hemodynamically stable IDA, FCM enables the rapid administration of high iron doses with low immunogenicity.Importantly, the observed improvements in Hb and ferritin levels are sustained for up to six months following a single IV infusion, aligning with the findings in our study, which demonstrated significant improvements in Hb, serum ferritin, RBC count, haematocrit, and MCH in subjects with severe IDA (P < 0.001 for all).

Conclusion
In conclusion, this study investigated the efficacy and safety of ferric carboxymaltose (FCM) in the treatment of iron deficiency anaemia (IDA) in a cohort of 100 patients across four locations in West Bengal, India.The results demonstrated significant improvements in various hematological parameters, including a substantial increase in haemoglobin levels, following FCM administration.The study also highlighted the absence of adverse events, showcasing a favorable safety profile of FCM in this population.
The use of FCM, a third-generation parenteral iron formulation, proved effective in addressing moderateto-severe IDA, aligning with existing evidence supporting its efficacy and safety.The rapid and substantial improvement in haemoglobin levels observed within four weeks of FCM administration emphasizes its efficiency in iron repletion, particularly in cases where oral preparations may be insufficient.The absence of adverse effects further supports the tolerability of FCM, a crucial factor in its consideration for widespread use.
The study contributes valuable real-world data, especially in the context of the high prevalence of anaemia in India.The findings underscore the potential of FCM as a cornerstone in the treatment of severe anaemia, advocating for its inclusion in targeted interventions and public health initiatives.Overall, this study adds to the growing body of evidence supporting FCM as a promising option in the management of iron deficiency anaemia.