Date Published: September 10, 2012
Publisher: Blackwell Publishing Ltd
Author(s): F Cremonini, J P Nicandro, V Atkinson, R Shringarpure, E Chuang, A Lembo.
Patients with irritable bowel syndrome with diarrhoea (IBS-D) experience restriction in daily activities and decreased health-related quality of life (QOL).
To investigate effects of alosetron on patient-reported health-related QOL, satisfaction and productivity in women with severe IBS-D.
A total of 705 women (severe IBS-D, Rome II criteria) randomised to alosetron 0.5 mg QD, 1 mg QD, 1 mg BID, or placebo for 12 weeks were studied. IBSQOL, treatment satisfaction, daily activities, and lost workplace productivity (LWP) were evaluated at randomisation and Week 12.
One or more doses of alosetron significantly improved all IBSQOL domains except for sexual function from baseline vs. placebo. The magnitude of IBSQOL changes was consistent with a clinically meaningful effect. Alosetron 0.5 mg QD and 1 mg BID significantly reduced IBS interference with social/leisure activities and LWP from baseline vs. placebo [social/leisure (mean ±S.E.) days lost: −6.7 ± 0.8, −7.0 ± 0.9, P < 0.01; LWP (mean ± S.E.) h lost: −11.0 ± 3.3, −21.1 ± 4.1, P < 0.05 respectively]. Significantly more patients treated with alosetron reported satisfaction vs. placebo. Improvements in IBSQOL, LWP, and treatment satisfaction significantly correlated with global improvement of IBS symptoms. The incidence of adverse events with alosetron was low with constipation being the most commonly reported event. A single case of ischaemic colitis occurred, in a patient receiving alosetron 0.5 mg QD. In women with severe IBS-D, alosetron treatment, including 0.5 mg QD, resulted in statistically significant and clinically relevant improvements in health-related QOL, restriction of daily activities and treatment satisfaction over placebo. IBS symptom improvement corresponded with positive changes in IBSQOL, LWP and treatment satisfaction.
The impact of the irritable bowel syndrome (IBS) reaches beyond abdominal pain and altered bowel habits. Patients suffering with IBS, compared to individuals without IBS, generally experience differing levels of restriction in daily activities (e.g. diminished workplace productivity and reduced physical/social functioning), worse psychological well-being and lower quality of life. The estimated total direct and indirect healthcare costs associated with IBS are sixfold higher compared to healthy individuals,1, 2 and IBS patients are more likely to undergo unnecessary abdominal surgeries than individuals without IBS.3, 4 The burden of IBS on psychosocial, economic, quality of life and daily function aspects is even greater in patients with severe and refractory symptoms.5 The estimated proportion of IBS patients considered to have severe symptoms ranges from 20% to 55%.6
Patients were enrolled from June 2003 to June 2005 at multiple study sites in the United States. Institutional Review Boards at each individual site approved the protocol. Patients provided written informed consent upon study entry. The efficacy data of alosetron on IBS symptom relief from this study have been previously reported.15 Details of the clinical trial are publicly accessible at clinicaltrials.gov, registration number: NCT00067561.
This randomised, placebo-controlled study demonstrated that alosetron administration, including 0.5 mg QD, was associated with improved measures of IBS-related quality of life and treatment satisfaction in women with severe IBS-D. Moreover, the 0.5 mg QD dose of alosetron was associated with improvements in lost workplace productivity, and resulted in fewer days of restriction of daily activities caused by IBS symptoms. The effects of alosetron on quality of life, workplace productivity and restriction of daily activities were moderately correlated with drug efficacy, as reflected by improvement of global IBS symptoms. Since there are limited clinical trial data on the important association between symptom improvement and health outcomes in IBS patients, it is significant when therapeutic responses to IBS treatments are reported to correspond with positive changes in health-related quality of life measures.29