Clinical Question: Is tegaserod effective for irritable bowel syndrome (IBS) without diarrhea?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Tegaserod is approved for use in women with constipation-predominant IBS. This manufacturer-sponsored study looked at the efficacy in a somewhat broader group of patients. The participants were men and women 18 to 65 years of age with IBS according to the Rome II criteria who did not have diarrhea as a predominant symptom. Although the difference is subtle, the group of patients with IBS without diarrhea as a predominant symptom is larger than the group with constipation-predominant IBS. Patients with mild symptoms, severe laxative dependence, or other gastrointestinal conditions were excluded from the study.
Patients were randomized (allocation concealed) to one of two groups: tegaserod in a dosage of 6 mg orally twice a day or matching placebo for 12 weeks. Patients were evaluated after four and 12 weeks of treatment, and again four weeks after treatment was withdrawn. The groups were similar at baseline, and analysis was by intention to treat. Of 327 patients randomized to receive tegaserod, 23 withdrew because of an adverse event, and 27 withdrew for other reasons, leaving 277 patients who completed treatment. Of 320 patients randomized to receive placebo, six withdrew because of an adverse event, and 25 withdrew for other reasons, leaving 287 patients who completed treatment.
The primary outcome measured was whether patients were responders, defined as answering yes at least 50 percent of the time in the first four weeks of treatment to the question, “Over the past week, do you consider that you have had satisfactory relief from your symptoms of IBS?” Patients in the tegaserod group were more likely to be responders in the first four weeks (26 percent versus 19 percent; absolute risk reduction [ARR] = 7 percent; number needed to treat [NNT] = 14). The researchers also looked at the mean proportion of patients getting satisfactory relief during the full 12-week study period, and again there was a modest benefit to tegaserod (34 percent versus 23 percent; ARR = 11 percent; NNT = nine).
Dropouts due to adverse events were more common in the tegaserod group (23 patients versus six patients in the placebo group), as was any adverse event (55 percent versus 50 percent). The most common adverse events were diarrhea and headache. The benefit was a bit less in men (ARR = 1.6 percent for the first four weeks, 10.5 percent for all 12 weeks), although the statistical significance for this subgroup analysis was not reported, and the total number of men (i.e., 91) was too small to support any conclusions.
Bottom Line: Tegaserod provides some modest benefit (NNT = 11 to 14) in women with IBS who do not have diarrhea as the predominant symptom. Although men appeared to experience some benefit as well, the number of men studied was too small to support any firm conclusions. (Level of Evidence: 1b)