A reply to Moris et al.

To the Editor: We are pleased to provide the data derived from the analysis that was requested by Moris et al. We have performed a second modified efficacy analysis now including baseline hepcidin levels instead of baseline hepcidin/ferritin ratio. In line with the previous analysis, this analysis provided proof for the existence of a relevant influence of baseline hepcidin levels on treatment efficacy. In line with the original presented data, we divided the participants again in two groups based on baseline hepcidin (baseline hepcidin below group median, or baseline hepcidin above group median of 9.7 μg/L). In patients with a low baseline hepcidin level treatment with esomeprazole resulted in a significant reduction in LIC of 1.29 mg Fe/g dw (95% CI [0.60–1.97]; p = 0.001) larger than placebo. After esomeprazole, there was a mean reduction of LIC of 1.07 mg Fe/g dw (SD 1.27) versus an increase of 0.11 mg Fe/g dw (SD 0.77) after placebo. In patients with a high baseline hepcidin level esomeprazole led to a nonsignificant increase in LIC of 0.31 mg Fe/g dw (95% CI [ 0.30 to 0.92]; p = 0.30) greater than placebo. After esomeprazole treatment, there was a mean increase in LIC of 0.13 mg Fe/g dw (SD 0.62) versus a reduction of 0.31 mg Fe/g dw (SD 0.70) after placebo treatment. Therefore, in line with Moris et al., we conclude that PPI treatment should be considered in those patients with either low baseline hepcidin levels, or low baseline hepcidin/ferritin ratio. One limitation of the trial is the underrepresentation of patients with more severe iron overload. As a consequence, the exchangeability of hepcidin and hepcidin/ferritin ratios remains to be proven in those patients with moderate-to-severe iron overload.