Results
Demographics
Figure 1 describes the progression of patients in the study. Full details of patients screened have been previously published. Of the 705 women with severe IBS-D who were randomised, at least 52% of patients in each treatment group completed the study. The primary reasons for premature discontinuation were adverse events (86 patients, 12%) and withdrawal of consent (92 patients, 13%). Compliance with study treatment evaluated from the telephone data entry system was similar between groups, with 87–93% of patients reporting >80% compliance.
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Figure 1.
Patient disposition. QD, once daily; BID, twice daily.
There were no significant differences in demographic features, including IBS symptom severity between the treatment arms at baseline (Table 1). All patients reported restriction of daily activities from IBS symptoms on ≥25% of days with actual restrictions on 68–70% of days.
Health-related Quality of Life Changes
Statistically significant improvements were observed for at least one alosetron dose in all IBSQOL domains relative to placebo, with the exception of sexual relations (Table 2).
Correlation of Health-related Quality of Life Changes With IBS Symptom Improvement
Correlations between Week 12 global improvement of IBS symptoms and changes from baseline in the nine IBSQOL domains are reported in Table 3 . For all nine IBSQOL scales, improvements in change from baseline scores were significantly correlated with Week 12 global improvement of IBS symptoms.
Productivity
Statistically significant reductions in LWP were observed in the 0.5 mg QD (decrease of 11.0 h; P < 0.05) and the 1 mg BID (decrease of 21.1 h; P < 0.001) groups compared with placebo (decrease of 7.2 h) (Figure 2). The change from baseline in LWP was negatively correlated with the Week 12 global improvement of IBS symptoms (Table 3), suggesting that reductions in LWP were associated with improvements in global IBS symptoms.
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Figure 2.
Mean number of hours of lost workplace productivity at baseline and Week 12 for the placebo (PBO) and alosetron treatment groups. BL, baseline; QD, once daily; BID, twice daily. *P < 0.05, ***P < 0.001, significantly different from placebo.
The number of days IBS symptoms caused restriction of daily activities (interfered with social/leisure activities) was significantly reduced in the 0.5 mg QD and 1.0 mg BID alosetron groups compared to placebo (P < 0.01) (Figure 3a). Although the number of days IBS symptoms interfered with household activities was reduced, the treatment differences did not reach statistical significance compared with placebo (Figure 3b).
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Figure 3.
Mean number of days IBS symptoms interfered with (a) social/leisure and (b) household activities at baseline and Week 12 for the placebo (PBO) and alosetron treatment groups. BL, baseline; QD, once daily; BID, twice daily. **P < 0.01, significantly different from placebo.
Treatment Satisfaction
Significant improvements in treatment satisfaction from baseline to Week 12 were observed in all treatment groups (P < 0.0001). At Week 12, significantly higher proportions of subjects in each alosetron dose group (P < 0.01) reported better satisfaction with their IBS medication compared with the placebo group (Figure 4). The number of subjects expressing treatment satisfaction with placebo increased from baseline by 29% to 45% after 12 weeks, representing a treatment difference of 21% for alosetron 0.5 mg QD vs. placebo at Week 12 (Figure 4). Greater satisfaction with IBS treatment at Week 12 was correlated with the Week 12 global improvement of IBS symptoms (Table 3).
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Figure 4.
Proportion of patients satisfied with their IBS treatment at baseline and Week 12 for the placebo (PBO) and alosetron treatment groups. BL, baseline; QD, once daily; BID, twice daily. **P < 0.01 significantly different from placebo, ***P < 0.0001 significantly different from baseline.
Safety
Safety results for this study have been previously reported. In summary, incidences of adverse events were similar across all treatment groups, with constipation being the most commonly observed adverse event. Patients experiencing adverse events were included in the analyses of patient-reported outcomes in this study. The incidence of constipation was dose-related in the alosetron groups (9%, 16%, and 19%, for the 0.5 mg QD, 1 mg QD and 1 mg BID groups respectively). Three serious adverse events were reported that were considered by investigators to be related to alosetron [two patients on 0.5 mg QD (bowel obstruction, ischaemic colitis]; one patient on 1 mg BID (faecal impaction)]. All three adverse events resolved shortly after discontinuation of treatment.