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In their long-term follow-up of prior randomised controlled trials of lubiprostone in constipation-predominant irritable bowel syndrome (IBS-C),[1] Chey and colleagues[2] provide us with an opportunity to gain valuable insights into two issues that are of considerable interest to the clinician: how well is this drug tolerated and are benefits sustained, in the longer term? The latter is especially important given the often reported complaint of our patients that ‘it only worked for a while and then my system seemed to get used to it’; ‘it’ being anything from a laxative to a prescription drug.

The data presented by Chey and colleagues appear reassuring at first look: responder rates, although not earth-shattering, do appear to be sustained, albeit in an open, uncontrolled study where everyone received the active agent. Furthermore, these long-term responses were still evident even when the data were adjusted to take account of dropouts. In assessing the real impact of the drug in IBS-C it must be remembered that 18.1% discontinued due to lack of efficacy, and 32% needed to take rescue medication, with only 58.2% completing the 36-week extension study.

So, valuable as these data are, they must, in terms of efficacy, and as conceded by the authors, be interpreted with caution bearing in mind that the preceding randomised controlled trials produced a therapeutic gain of 7–8% over a 12- to 16-week study period,[1] a far cry from the 37–44% observed at the end of the extension study. As would be predicted from the mechanism of action of the drug, the effects on pain and discomfort were more modest.

The experience with adverse events in the long-term extension was also, in general, reassuring. There were no surprises and, as expected, given the mode of action of the drug,[3] diarrhoea was one of the most common adverse events. Not as well understood, although again well described in the controlled studies,[1] is the 11% incidence of nausea; how a drug that seems to act exclusively on chloride channels in the colon and appears to be devoid of significant enteric sensori-motor effects[4, 5] can cause symptoms thought to originate from the proximal gut remains to be explained. Fortunately, withdrawal, due to adverse events, was rare.

The bottom line: reassuring data on long-term safety and efficacy but, as is often the case, controlled data are needed.

Acknowledgement

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  2. Acknowledgement
  3. References

Declaration of personal interests: Eamonn M. M. Quigley has served as a consultant, advisory board member and/or speaker for Movetis, Shire, Ironwood, Almirall, Janssen, Yakult, Procter and Gamble and Alimentary Health, and has been a non-executive board member of, and share-holder in, Alimentary Health. Declaration of funding interests: Eamonn M. M. Quigley has received research funding from Merck, Alimentary Health and Norgine.

References

  1. Top of page
  2. Acknowledgement
  3. References