To the editors:
We read the randomized control trial (RCT) by Ke et al. with interest.1 The authors reported the efficacy of prucalopride compared with placebo in the treatment of chronic idiopathic constipation (CIC) in the Asia-Pacific region. All RCTs of prucalopride, to date, have been conducted among Western populations, so the authors are to be congratulated for performing the first trial of the drug in Asia.
Data on the prevalence of CIC in Asia are sparse, but a recent systematic review and meta-analysis estimated that the prevalence was 11% in South East Asia, which was only slightly lower than that in European and North American populations.2 The trial demonstrated that prucalopride was more effective than placebo for the treatment of CIC in Asian patients, with a number needed to treat (NNT) of 4. In a recent meta-analysis of seven placebo-controlled trials of prucalopride conducted in North American and European populations,3 five used the same primary outcome measure as that of Ke et al. (≥3 complete spontaneous bowel movements per week), and the NNT when data from these five studies were pooled was lower at 7.
However, this apparent increased efficacy of the drug in Asians with CIC seems to come with a price. There was no detailed discussion of adverse event rates in the trial, and no statistical tests of significance were applied to these data, but total and individual adverse events (including abdominal pain, headache, nausea, and diarrhea) were all significantly commoner with active therapy. Despite the authors’ assertions that prucalopride was well-tolerated, the absolute difference in adverse event rates between the two treatment arms was similar to that for response to therapy, leading to a number needed to harm with prucalopride of 4. Interestingly, when total adverse events data from this trial are pooled with the four previous RCTs that compared a 2 mg dose of prucalopride with placebo, the results of Ke et al.’s. study are quite different (Fig. 1).
In summary, the results of this trial demonstrate that prucalopride is superior to placebo in the treatment of CIC in Asians. However, the balance of risks and benefits may be different in this population.