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Treatment of pernicious anemia: Which is the best option?
Autoimmunity Reviews 13 (2014) 779
Contents lists available at ScienceDirect
Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev
Letter to the Editor Treatment of pernicious anemia: Which is the best option? We thank Dr. Andres for his interest in our review on the diagnosis and classification of pernicious anemia [1]. We are aware that oral administration of vitamin B12 has been proposed as an alternative to intramuscular injection. However, we based our very brief (and thus not exhaustive) description on the treatment of pernicious anemia on a recent systematic review [2] showing that there is still only limited evidence from randomized controlled trials that oral vitamin B12 is an effective short-term treatment for vitamin B12 deficiency. Conclusions from this review state that current evidence has serious limitations as it includes only a few open studies with relatively short follow-up periods, unclear methods of randomization and no intention-to-treat analysis. Even in a review authored by Andres and Dali-Youcef [3] it is said that the procedure for oral cobalamin therapy has not yet been completely validated in clinical practice, especially with respect to long-term efficacy. Another reason why we were cautious is that only a minority of the patients described in the studies cited were affected by pernicious anemia. Most of them had vitamin B12 deficiency that may have resulted from other causes, such as malabsorption, ileal resection or (rarely) insufficient dietary intake. To our knowledge, oral vitamin B12 is rarely prescribed other than in Scandinavia and Canada where it accounts for 6% of B12 treatment [4]. Probably, this “medicine's best kept secret” is less commonly used than injections because it requires much greater patient compliance. If patients did not undergo monthly or quarterly intramuscular injections, they would need to take one tablet of vitamin B12 per day. It is certainly debatable which of the two options is more advantageous to the doctor and the patient, and for which method compliance is more assured. Lastly, because of variability in absorption, lower oral doses may be not completely effective in some patients with pernicious anemia. Because of the possibility of erratic absorption, it is most appropriate to use oral treatment after the patient's cobalamin status has been normalized with parenteral treatment [5].
http://dx.doi.org/10.1016/j.autrev.2014.02.001 1568-9972/© 2014 Elsevier B.V. All rights reserved.
Notwithstanding these limitations, we recognize that Dr. Andres' advice warrants consideration and, indeed, we regret having omitted a more complete sentence stating that high-dose oral vitamin B12 administration has been proposed and that, although limited studies have been conducted to date, they have shown that oral treatment can be a promising alternative to intramuscular vitamin B12 administration [6].
References [1] Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev 2014;13:565–8. [2] Butler CC, Vidal-Alaball J, Cannings-John R, McCaddon A, Hood K, Papaioannou A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 2006;23:279–85. [3] Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. Q J Med 2009;102:17–28. [4] Graham ID, Jette N, Tetroe J, Robinson N, Milne S, Mitchell SL. Oral cobalamin remains medicine's best kept secret. Arch Gerontol Geriatr 2007;44:49–59. [5] Schrier SL. Diagnosis and treatment of vitamin B12 and folate deficiency. www. uptodate.com/store; 2014. [Last access: February 20th, 2014]. [6] Lin J, Kelsberg G, Safranek S, Neher JO. Is high-dose oral B12 a safe and effective alternative to a B12 injection? J Fam Pract 2012;61:162–3.
Nicola Bizzaro Laboratory of Clinical Pathology, San Antonio Hospital, Tolmezzo, Italy Corresponding author at: Laboratory of Clinical Pathology Ospedale S. Antonio via Morgagni, 18 33028 Tolmezzo (UD) Italy. Tel.: +39 0433 488261; fax +39 0433 488697. E-mail address: [email protected].
Antonio Antico Laboratory of Clinical Pathology, Civic Hospital, Santorso, Italy
20 February 2014
Contents lists available at ScienceDirect
Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev
Letter to the Editor Treatment of pernicious anemia: Which is the best option? We thank Dr. Andres for his interest in our review on the diagnosis and classification of pernicious anemia [1]. We are aware that oral administration of vitamin B12 has been proposed as an alternative to intramuscular injection. However, we based our very brief (and thus not exhaustive) description on the treatment of pernicious anemia on a recent systematic review [2] showing that there is still only limited evidence from randomized controlled trials that oral vitamin B12 is an effective short-term treatment for vitamin B12 deficiency. Conclusions from this review state that current evidence has serious limitations as it includes only a few open studies with relatively short follow-up periods, unclear methods of randomization and no intention-to-treat analysis. Even in a review authored by Andres and Dali-Youcef [3] it is said that the procedure for oral cobalamin therapy has not yet been completely validated in clinical practice, especially with respect to long-term efficacy. Another reason why we were cautious is that only a minority of the patients described in the studies cited were affected by pernicious anemia. Most of them had vitamin B12 deficiency that may have resulted from other causes, such as malabsorption, ileal resection or (rarely) insufficient dietary intake. To our knowledge, oral vitamin B12 is rarely prescribed other than in Scandinavia and Canada where it accounts for 6% of B12 treatment [4]. Probably, this “medicine's best kept secret” is less commonly used than injections because it requires much greater patient compliance. If patients did not undergo monthly or quarterly intramuscular injections, they would need to take one tablet of vitamin B12 per day. It is certainly debatable which of the two options is more advantageous to the doctor and the patient, and for which method compliance is more assured. Lastly, because of variability in absorption, lower oral doses may be not completely effective in some patients with pernicious anemia. Because of the possibility of erratic absorption, it is most appropriate to use oral treatment after the patient's cobalamin status has been normalized with parenteral treatment [5].
http://dx.doi.org/10.1016/j.autrev.2014.02.001 1568-9972/© 2014 Elsevier B.V. All rights reserved.
Notwithstanding these limitations, we recognize that Dr. Andres' advice warrants consideration and, indeed, we regret having omitted a more complete sentence stating that high-dose oral vitamin B12 administration has been proposed and that, although limited studies have been conducted to date, they have shown that oral treatment can be a promising alternative to intramuscular vitamin B12 administration [6].
References [1] Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev 2014;13:565–8. [2] Butler CC, Vidal-Alaball J, Cannings-John R, McCaddon A, Hood K, Papaioannou A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 2006;23:279–85. [3] Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. Q J Med 2009;102:17–28. [4] Graham ID, Jette N, Tetroe J, Robinson N, Milne S, Mitchell SL. Oral cobalamin remains medicine's best kept secret. Arch Gerontol Geriatr 2007;44:49–59. [5] Schrier SL. Diagnosis and treatment of vitamin B12 and folate deficiency. www. uptodate.com/store; 2014. [Last access: February 20th, 2014]. [6] Lin J, Kelsberg G, Safranek S, Neher JO. Is high-dose oral B12 a safe and effective alternative to a B12 injection? J Fam Pract 2012;61:162–3.
Nicola Bizzaro Laboratory of Clinical Pathology, San Antonio Hospital, Tolmezzo, Italy Corresponding author at: Laboratory of Clinical Pathology Ospedale S. Antonio via Morgagni, 18 33028 Tolmezzo (UD) Italy. Tel.: +39 0433 488261; fax +39 0433 488697. E-mail address: [email protected].
Antonio Antico Laboratory of Clinical Pathology, Civic Hospital, Santorso, Italy
20 February 2014