Lubiprostone for Multiple Sclerosis-Associated Constipation

Background: Approximately 70% of patients with MS have bowel dysfunction most commonly seen as constipation, occurring in 43% of MS patients. The psychosocial impact of this problem is often underestimated, but bowel problems clearly reduce quality of life in patients with MS and can be an important contributor to unemployment and social withdrawal. We are not aware of any prior therapeutic trials specifically for MS-associated bowel dysfunction.

Objectives: To determine the effect of lubiprostone 24 mcg twice daily on spontaneous bowel movements in patients with MS-associated constipation. 

Methods: Single-center, randomized, double-blind, placebo-controlled, parallel-groups study.  Patients were monitored on lubiprostone or placebo for 21 days following a 14-day baseline/washout period.

Results: Of the 40 patients considered for randomization at baseline a total of 21 were assigned to one of the two treatment groups , 18 were ineligible due to a higher than expected baseline spontaneous bowel movement (SBM) count, and 1 was unable to schedule visits. All baseline measures were comparable between the Randomized and Not Randomized groups with the exception of SBM count and age. The significant difference in SBM count was expected since this was used as a criterion for eligibility. Of the patients randomized, all baseline measures were comparable between the placebo and lubiprostone treatment groups, with the exception of age where there is a 6 year difference. When all patients were included in the analysis regardless of completion of the trial and it was assumed the observed SBM rate of the patients who stopped early would have continued for the remainder of the follow-up period there was a significant difference in the within patient change in average weekly SBM count (p = 0.04). Of the three patients who stopped early two of the patients stopped after only two days due to a high frequency of diarrhetic events. In fact, when all three patients who stopped early are excluded from the analysis completely, the difference is no longer significant between the two treatment groups (p = 0.18). In either scenario where it is assumed the observed rate does not continue as observed over the remainder of the follow-up period, the difference between the two treatment groups is still not significant (p = 0.57 and p = 0.29).

Conclusions: BWCS change did not differ significantly between the two treatment groups, yet SBM appeared to increase more in the lubiprostone group. This would lead one to believe that lubiprostone was effective in increasing the number of SBM's at the price of an increase in diarrheic events, yet these adverse events did not heavily affect quality of life (as measured by the BWCS). Furthermore, for those patients who stopped treatment early due to adverse events, the BWCS did not show a clinically significant increase. This would indicate that lubiprostone is effective in relieving constipation, but it comes with the increased risk of diarrhea.