Background and Objectives: Corpus atrophic gastritis (CAG) is associated with vitamin B₁₂ deficiency due to impaired gastric acid and intrinsic factor secretion. Untreated vitamin B₁₂ deficiency can lead to pernicious anemia, severe neurological consequences, and acute cardiocerebral-vascular events. Timely vitamin B₁₂ supplementation is relevant; however, the dosage of intramuscular (IM) vitamin B₁₂ supplementation has not been standardized to date. The objective was to assess the efficacy of a 1st and 2nd treatment schedule of IM-cyanocobalamin treatment in CAG patients with vitamin B₁₂ deficiency at long-term follow-up and to identify the predictors of increased cyanocobalamin requirement. Methods: This monocentric real-life cohort study included 213 CAG patients with vitamin B₁₂ deficiency. Inclusion criteria were adult age, histological diagnosis of CAG with vitamin B₁₂ deficiency (<220 pg/mL), and follow-up of more than 12 months. The 1st-treatment-schedule (TxA) was 5000 µg IM cyanocobalamin every 5 days for 3 times, followed by 5000 µg IM cyanocobalamin every 3 mos (20,000 µg/yr); the 2nd-treatment-schedule (TxB) was 5000 µg IM cyanocobalamin every 5 days for 3 times, followed by 5000 µg IM cyanocobalamin every 2 mos (30,000 µg/yr). The treatment endpoint was serum vitamin B₁₂ normalization. Clinical-biochemical follow-up was scheduled every 12 ± 6 mos: patients who satisfied the endpoint maintained the TxA, otherwise, TxB was prescribed. Results: Of the 213 CAG patients with vitamin B₁₂ deficiency, 48.3% had anemia, and 26.3% macrocytosis without anemia. TxA efficaciously corrected vitamin B₁₂ deficiency in 146 (68.5%) patients, maintaining efficacy until the longest available follow-up (42.2 ± 2.6 months). The remaining 67 patients (31.5%) were switched to TxB due to persistent vitamin B₁₂ deficiency observed at 12 (6–36) months and were maintained until the longest available follow-up (50.2 ± 4.1 months). At the longest available follow-up, a significant increase in Hb (TxA: 11.9 ± 0.2 to 13.1 ± 0.1 g/dL, p < 0.001; TxB: 12.2 ± 0.3 to 13.6 ± 0.2 g/dL, p = 0.003) and serum vitamin B₁₂ (TxA: 168 ± 7 to 402 ± 19 pg/mL, p < 0.0001; TxB: 157 ± 12 to 340 ± 24 pg/mL, p < 0.0001) was shown in both schedules. A significant decrease in MCV was shown in TxB only (p = 0.0003). In logistic regression, switching to TxB was significantly associated with severe corpus intestinal metaplasia (OR 11.0, 95% CI 2.8–43.7), macrocytosis at CAG diagnosis (OR 2.7, 95% CI 1.2–6.3), and male sex (OR 2.4, 95% CI 1.1–5.2). Conclusions: In this real-world setting, at long-term follow-up, nearly 70% of CAG patients with vitamin B₁₂ deficiency restored their vitamin B₁₂ levels with 20,000 µg/yr of cyanocobalamin, while the remaining 30% required 30,000 µg/yr. Male vitamin B₁₂-deficient CAG patients with advanced gastric damage and severe macrocytosis required higher dosages of cyanocobalamin. They should be carefully monitored to avoid suboptimal supplementation and potentially dangerous consequences of vitamin B₁₂ deficiency.

Background/Objectives: Autoimmune gastritis (AIG), celiac disease (CD), and gastric surgery (GS) often cause iron deficiency anemia (IDA) due to iron malabsorption. In this clinical context, IDA treatment is often challenging. The first-line IDA treatment is oral iron supplementation followed by intravenous (IV) iron administration when ineffective or not tolerated. Ferric carboxymaltose (FCM) showed efficacy in various clinical settings. Prospective data evaluating the efficacy of IV FCM in IDA patients secondary to iron malabsorption are scant. The aim of the current study was to assess the tolerability, efficacy, and QoL impact of IV FCM for the treatment of IDA patients with iron malabsorption. Methods: Study design: single-center, prospective observational study: n = 37 adults with AIG, CD, or GS with IDA receiving IV FCM were consecutively included. Endpoints were (i) safety tolerability, (ii) efficacy on IDA recovery (Hb normalization), and (iii) QoL impact. At baseline (T0) and 12 weeks after treatment (T12), a QoL-SF12 questionnaire was assessed. Complete blood count (CBC) and iron status (ferritin, iron, transferrin, transferrin saturation (TS)) were assessed at T0, 4 weeks (T4), and T12 after treatment. Results: Of the 37 IDA patients, 19 (51.4%) had AIG, 9 (24.3%) CD, and 9 (24.3%) GS; Based on Ganzoni’s formula, 24 (64.9%) patients received a single IV FCM infusion (mean ± SEM dosage of 975 ± 12 mg); 13 (35.1%) required two IV infusion sessions with a mean ± SEM cumulative dose of 1400 ± 77 mg. One patient (2.7%) experienced mild adverse events without need for treatment interruption or hospitalization. At T0, anemia was moderate in 7 (18.9%) patients and severe in 1 (2.7%). IDA recovery was achieved in 26 (70.3%) patients at T4 and in 29 (78.4%) at T12. At T4, mean ± SEM Hb increased from 10.8 ± 0.2 g/dL to 12.7 ± 0.1 g/dL, ferritin from 28.5 ± 11.2 ng/mL to 188.2 ± 25.7 ng/mL, and TS from 6.7 ± 0.5% to 23.7 ± 1.9% (p < 0.0001). At T12, mean ± SEM Hb further increased to 13.1 ± 0.2 g/dL (p < 0.05 vs. T4), ferritin slightly decreased to 125 ± 26.7 ng/mL, and TS to 22.7 ± 2.8%. At T12, nonsignificant increases in QoL scores relative to baseline were observed. Conclusions: IV FCM is a safe and effective treatment leading to IDA recovery in nearly 80% of patients at T12. Thus, when oral iron treatment is not feasible or has failed, IV FCM treatment might be considered a first-line therapeutic option for IDA consequent to iron malabsorption.