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

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 100-300 µg/L have not been well established. The aim of this study is to assess the efficacy and safety of IV iron in RLS patients 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 RLS patients treated with 1000 mg of ferric carboxymaltose (FCM), with baseline serum ferritin concentrations <300 µg/L. Patients were divided into two groups: Group A (serum ferritin <100 µg/L) and Group B (serum ferritin 100-300 µg/L). We compared changes in symptom severity (IRLS scale), substantia nigra iron deposits (SNEI), and systemic iron parameters.

Results: Both groups showed similar improvements in IRLS scores and SNEI. Serum ferritin increased significantly in Group B post-treatment, while no major differences were observed in TSAT or serum transferrin levels between the two groups. Regarding risk of iron overload, only 2 patients (Group B) showed a TSAT >45%. No harm resulted to either patient, with no hepatic dysfunction observed.

Conclusions: IV iron therapy is effective in RLS patients 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 RLS patients.