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Sirs,

We read the review by Chouchana et al.[1] with interest. We think this is a comprehensive and well-written update on the topic of thiopurine pharmacogenetics for IBD, particularly interesting because of recent prospective studies that were unable to find an association between thiopurine metabolites concentration and clinical response in IBD, which should be put in the perspective of current literature.

However, we underline that the statement that thiopurine-S-methyl-transferase (TPMT) activity does not seem to be altered in a relevant manner by age may not be perfectly accurate, particularly for children with IBD. Indeed, there are previous reports that young subjects have higher TPMT activity compared to older ones: Serpe et al. showed that TPMT activity is significantly higher in wild-type children than wild-type adults and, in particular, wild-type infants (0.08–2 years) had a 9% higher TPMT activity than other wild-type groups[2]; McLeod et al. reported similarly that in newborns TPMT activity and TPMT protein concentration in erythrocytes are 50% higher than in healthy adults.[3] Results consistent with these observations have been reported by other authors.[4, 5]

Moreover, a recent study showed that IBD patients 6 years of age or younger treated with thiopurines had an 85% increase in probability of response if taking a dose >3.0 mg/kg/day, that is considered the upper limit for the safe dose of this medication in the general adult population, compared to a dose of 2–3 mg/kg/day. These data support the view that closely monitored dose escalation beyond the standard dosing range, including evaluation of thiopurine metabolites, may be effective and well tolerated[6] in very young patients. Therefore, we think that prospective studies evaluating the possibility of treating young children with IBD with higher doses of thiopurines, in the perspective of their higher TPMT activity, while monitoring thiopurine metabolite concentrations may be of importance to improve treatment of this particularly relevant population of patients.

Acknowledgements

Declaration of personal interests: Dr Gabriele Stocco is supported by Associazione Genitori Malati Emopatici Neoplastici Friuli Venezia Giulia. Dr Sara De Iudicibus is supported by Associazione Italiana per i Bambini ed i Giovani con Malattie Infiammatorie Croniche Intestinali. Declaration of funding interests: None.

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