Efficacy and safety of intravenous iron in patients with restless legs syndrome with normal serum ferritin levels: a stratified subanalysis.

STUDY OBJECTIVES: Restless legs syndrome (RLS) has long been associated with iron deficiency. Current clinical guidelines recommend intravenous (IV) iron therapy for patients with serum ferritin levels ≤ 100 µg/L, but the effectiveness and safety of IV iron in patients with ferritin levels between 100 and 300 µg/L have not been well established. The aim of this study is to assess the efficacy and safety of IV iron in patients with RLS with serum ferritin levels both below and above the 100 µg/L threshold, hypothesizing no significant differences in therapeutic response between these groups. METHODS: We conducted a longitudinal retrospective analysis of 58 patients with RLS treated with 1,000 mg of ferric carboxymaltose, with baseline serum ferritin concentrations < 300 µg/L. Patients were divided into 2 groups: group A (serum ferritin < 100 µg/L) and group B (serum ferritin 100-300 µg/L). We compared changes in symptom severity (International Restless Legs Syndrome Severity Scale), substantia nigra iron deposits (substantia nigra echogenicity index), and systemic iron parameters. RESULTS: Both groups showed similar improvements in International Restless Legs Syndrome Severity Scale scores and substantia nigra echogenicity index. Serum ferritin increased significantly in group B posttreatment, while no major differences were observed in transferrin saturation or serum transferrin levels between the 2 groups. Regarding risk of iron overload, only 2 patients (group B) showed a transferrin saturation > 45%. No harm resulted to either patient, with no hepatic dysfunction observed. CONCLUSIONS: IV iron therapy is effective in patients with RLS without hepatic iron overload with serum ferritin levels ranging from 100-300 µg/L. These findings challenge current guidelines and suggest that IV iron could be considered for a broader range of patients with RLS. CITATION: Garcia-Malo C, Garcia-Borreguero D, Silber MH. Efficacy and safety of intravenous iron in patients with restless legs syndrome with normal serum ferritin levels: a stratified subanalysis. J Clin Sleep Med. 2025;21(12):2023-2029.