Efficacy and Safety of Alosetron in Women with Irritable Bowel Syndrome
abstract & commentary
Synopsis: Alosetron was well tolerated and clinically effective in alleviating pain and bowel-related symptoms in this population of women with IBS.
Source: Camilleri M, et al. Lancet 2000;355:1035-1040.
In this study, the efficacy of the new 5-ht3 receptor-antagonist alosetron was evaluated in 647 female patients with irritable bowel syndrome (IBS). Treatment with alosetron 1 mg b.i.d. or placebo was for 12 weeks followed by a four-week post-treatment period. The primary evaluation end point was adequate relief of pain and discomfort. Over the evaluation period, the drop-out rates were 24% and 16% for alosetron- and placebo-treated groups, respectively—the difference in drop-out rates being attributed to a higher rate of occurrence of constipation in the alosetron group. More patients in the alosetron group reported adequate relief at three months: 41% vs. 29%. Constipation occurred in 30% and 3% of the alosetron and placebo groups, respectively. Camilleri and colleagues conclude that alosetron was well tolerated and clinically effective in alleviating pain and bowel-related symptoms in this population of women with IBS.
Comment by Eamonn M. M. Quigley, MD
IBS remains a common and clinically challenging problem in primary care and subspecialty practices. There have been, however, significant advances in our understanding of the pathophysiology of this condition with visceral hypersensitivity and/or hyperalgesia attracting particular attention. Basic research has, in turn, revealed a significant role for serotonin (5-HT)-receptors, and the 5-HT3-receptor in particular, in the mediation of visceral sensation. Several antagonists to this receptor have been developed for, and tested in, functional bowel disorders; alosetron is the first to enter clinical practice and represents, therefore, a new departure in the therapy of IBS. How good is it? As this, and prior studies have demonstrated, alosetron is consistently and significantly superior to placebo in relieving pain and discomfort; two of the cardinal symptoms of IBS. Though the therapeutic gain may, at first sight, appear modest it must be viewed in the context of a disorder where quotable P values are a distinct rarity in clinical trials! Alosetron may not suit all patients; studies to date have shown efficacy only in females and especially in those with the somewhat less common diarrhea-predominant variety of the disorder. As illustrated by this study, constipation is a significant side effect issue and its use is probably inadvisable in those with a constipation-predominant form of IBS. How about its efficacy among those with what is, perhaps, the most common manifestation, namely, the "alternator," who alternates between diarrhea and constipation? We await the outcome of clinical trials. Comparisons with tricyclic and serotonin reuptake inhibitor classes of antidepressants as well as simple anti-diarrheals will also be of interest.
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