Oral versus intramuscular cobalamin treatment in megaloblastic anemia: A single-center, prospective, randomized, open-label study

Background: Cobalamin (vitamin B12) deficiency, the most common cause of mega-loblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (PO) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. Objective: This study assessed the effects and cost of PO versus IM cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. Methods: This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged ≥ 16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-μg cobalamin PO once daily for 10 days (PO group) or 1000-μg cobalamin IM once daily for 10 days (IM group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Results: Sixty patientss completed the study 26 in the PO group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the IM group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the PO group, at days 30 and 90, all hematologic parameters changed signiificantly versus day 0 (mean hemoglobin levels increased [both P < 0.001]; mean corpuscular volume decreased [both P < 0.001]; mean white blood cell count increased [day 30, P < 0.01; day 90, P < 0.001]; and mean platelet count increased [both P < 0.001]). The mean serum vitamin B12 concentration incerased significantly from day 0 to 90 (P < 0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the PO group and 9 of 12 patients (75.0%) in the IM group at day 30. Conclusions: In this study of patients with megaloblastic anemia due to cobalamin deficiency, PO cobalamin treatment was as effective as IM cobalamin treatment. PO treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of PO cobalamin treatment.