Treatment of anaemia in inflammatory bowel disease: authors’ reply

Authors

  • A. de Silva,

    1. Queen Mary School of Medicine and Dentistry, and Barts and the London, Centre for Gastroenterology, Institute of Cell and Molecular Science, London, UK
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  • D. S. Rampton

    1. Queen Mary School of Medicine and Dentistry, and Barts and the London, Centre for Gastroenterology, Institute of Cell and Molecular Science, London, UK
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Sirs,

We thank Dr Koutroubakis et al. for their comments. We shall not repeat all the theoretical, animal and anecdotal clinical evidence about the possible adverse effects of oral iron to which they refer, and which prompted us to do our prospective comparative study to assess the efficacy, tolerability and safety of oral ferrous sulphate in patients with iron deficiency anaemia because of inflammatory bowel disease and other causes.1 We would like, however, to allude to their interpretation of our data and that of others.2, 3

In particular, in relation to the possible risk of increased disease activity in response to oral iron in our study,1 we would like to emphasize that only one measure, the Simple Clinical Colitis Activity Index (SCCAI) showed a statistically significant deterioration; all the other changes listed by Dr Koutrabakis, most of which were minimal in clinical terms, unsurprisingly failed to reach the P < 0.05 level. As we pointed out in the paper, only one patient with ulcerative colitis, who incurred a definite relapse within 3 days of starting on iron, showed a rise in SCCAI, which was associated with rectal bleeding: in every other instance, the increased SCCAI score was because of symptoms such as abdominal pain which could well have been because of the non-specific gastro-intestinal side effects of oral ferrous sulphate, which we found to be as common in patients without as with inflammatory bowel disease.

Perhaps we could add a few comments about the two published clinical studies to which Dr Koutrabakis refers. 2, 3 Neither, unfortunately, were double-blind: without such a trial design, it is impossible validly to compare the efficacy or side effects of oral and intravenous (i.v.) iron. In the cross-over study,2 although it was claimed that oral ferrous fumarate increased disease activity on the basis of symptom scores, the changes recorded could have been, as indicated above, because of iron intolerance rather than an increase in disease activity; indeed, oral ferrous fumarate, like i.v. iron-sucrose, did not alter either C-reactive protein or faecal calprotectin. More importantly perhaps, iron–sucrose injections actually increased plasma malondialdehyde and reduced vitamin C and betacarotene levels, indicating a systemic pro-oxidant effect, which was not seen after oral iron therapy in that, or in our own study.

We would like to restate our finding that in only two of 33 patients was relapse associated with, if not necessarily because of, oral ferrous sulphate therapy. However, we fully agree that our own trial may have turned out to be insufficiently powered to detect a small difference in the tolerability or safety of oral iron between patients with anaemia because of inflammatory bowel disease or other causes. What is clearly needed, as we and Schroder et al.3 concluded in our papers, is a large randomized, double-blind, longer-term controlled trial to compare oral iron and i.v. iron–sucrose in well-characterized patients with inflammatory bowel disease. Such a study will need to recruit only iron-naïve patients if bias because of selection of iron-tolerant, or exclusion of iron-intolerant subjects is to be avoided. Until we have such data, it is difficult to justify the use of the more inconvenient and expensive i.v. preparation except in individual patients with proven failure of response or intolerance to oral iron therapy.

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