Can Lubiprostone Improve PEG-based Colonoscopy Prep?

Abstract & Commentary

By Malcolm Robinson, MD, FACP, FACG, AGAF, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson reports no financial relationship to this field of study.

Synopsis: Lubiprostone, the new drug for idiopathic constipation, improved PEG-based colonoscopy preparation.

Source: Stengel JZ, Jones DP. Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: A randomized, double-blind, placebo-controlled trial. Am J Gastroenterol 2008;103:2224-2230.

Although colonoscopy is widely recommended as a screening tool for the detection of polyps and early colon cancer, as well as for the diagnosis of many other important disorders, colon preparation prior to colonoscopy has been a major obstacle to patient acceptance. Poor preparations make colonoscopy difficult, potentially more dangerous, and impair diagnostic accuracy. Polyethylene glycol electrolyte solutions (PEG) are commonly used for colon cleansing, and they are considered to be generally safe and potentially effective. However, the high volumes that have to be consumed by patients are often poorly tolerated. For this reason, some clinicians have adopted a split-dose regimen that involves drinking half the solution the evening before the procedure and the other half early the next morning. To purge remaining liquid within the colonic lumen along with residual fecal material, bisacodyl tablets are often added to the PEG regimen. However, a significant number of patients experience bisacodyl-related abdominal cramping and/or nausea. Lubiprostone (Amitiza™) is a recently approved medication for the treatment of idiopathic constipation that stimulates the secretion of a chloride-rich fluid into the colonic lumen without affecting colonic fluid and electrolyte absorption. Lubiprostone is effective for the treatment of chronic constipation and constipation-predominant IBS. It is generally quite well tolerated. The present study enrolled 200 patients who were referred for colon cancer screening. All received split-dose PEG, and half took lubiprostone as a 24 µg oral gel cap at noon the day before the procedure and half received a matching placebo. All patients consumed a regular diet until 4:00 p.m. the day prior to colonoscopy and clear liquids thereafter until the time of the procedure. Endoscopists were blind to treatment allocation. The validated 5-point Ottawa bowel preparation scale was used to rate each section of the colon for cleanliness (right, mid, rectosigmoid). A 14-point scale for the amount of residual fluid was also utilized. Participants rated their degree of satisfaction with the colon preparation regimen using a 5-point scale. Ultimately, 94 patients completed each arm of the study. Mean age for participants was about 55 years. Gender and other clinical characteristics were evenly divided. Bowel preparation quality was superior in all colon segments in the patients who received lubiprostone (P < 0.001). There was no significant difference between active drug and placebo in the amount of residual colon fluid. The time required to complete the colonoscopy was lower in lubiprostone recipients (P = 0.021) Lubiprostone was preferred by patients in terms of the overall preparation experience (P = 0.003), and no difference in any adverse events was identified between active drug and placebo. The authors point out that these outpatients are likely to have had better colonoscopy preparation results than might have occurred in inpatients with their immobility and comorbidities. The study was funded by Takeda Pharmaceuticals.

Commentary

There is no doubt that colonoscopy preparation remains unsatisfactory for many patients, and poor colon preparation continues to occur frequently. Anything that might improve colonoscopy preparation would be most welcome. It appears that the anti-constipation drug lubiprostone offers a promising adjunct to PEG-based colon cleansing prior to colonoscopy. There is little doubt that the active drug provided significant benefits when compared to placebo. However, as the authors themselves point out, the conventional adjunct to PEG is bisacodyl. It seems to me that the ideal lubiprostone study would have compared lubiprostone plus PEG to a PEG preparation that utilized bisacodyl. Perhaps such a study is already planned, and I sincerely hope that this is the case. Meanwhile, we really don't know whether lubiprostone is a good alternative to bisacodyl. It certainly will be more expensive. A comparative study using bisacodyl in one arm and lubiprostone in the other arm would have uncertain results, and pharmaceutical companies often avoid performing studies where the outcome cannot be reasonably well predicted.