Eric G. Carter

Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome ☆

OBJECTIVES:Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients. The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind, randomized, placebo-controlled study.METHODS:Female IBS patients with lack of satisfactory control of bowel urgency were randomized 2:1 to alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS Global Improvement (responder defined as patient-reported moderate or substantial improvement in IBS symptoms) and improvements in bowel function (stool frequency, consistency, and sensation of incomplete evacuation).RESULTS:A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p < 0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.CONCLUSIONS:Alosetron is effective at managing bowel urgency in women with diarrhea-predominant IBS. The IBS Global Improvement assessment correlated with improvements in bowel function and may be a useful tool in future IBS clinical trials.

Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: Results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain

&NA; Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu‐opioid receptor (PAM‐OR) antagonist, in subjects with non‐cancer pain and opioid‐induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2‐week baseline period, 522 subjects reporting <3 spontaneous bowel movements (SBMs)/week (with ⩾25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to ⩾30 mg oral morphine/day were randomized to alvimopan 0.5 mg twice daily (BID), 1 mg once daily (QD), 1 mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5 mg BID (+1.71 mean SBMs/week), alvimopan 1 mg QD (+1.64) and alvimopan 1 mg BID (+2.52); P < 0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The alvimopan 0.5 mg BID regimen demonstrated the best benefit‐to‐risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia.

Effect of alosetron on bowel urgency and global symptoms in women with severe, diarrhea-predominant irritable bowel syndrome: Analysis of two controlled trials☆

BACKGROUND & AIMS The aim of this study was to assess the effect of alosetron on bowel urgency and irritable bowel syndrome (IBS) global improvement in diarrhea-predominant IBS (D-IBS). METHODS Women with a lack of satisfactory bowel urgency control at least 50% of the time during screening were randomized to receive alosetron 1 mg (n = 246) or placebo (n = 246) twice daily. The primary end point was the percentage of days with satisfactory control of bowel urgency. The response rate for the IBS global improvement scale (GIS) was a secondary end point. GIS responders were patients who recorded either moderate or substantial improvement in IBS symptoms relative to the way they felt before entering the study. Other end points included improvement in stool frequency, stool consistency, and percentage of days with incomplete evacuation. Further analyses were performed on a subset of patients who had at least 10 of 14 days during screening (>/=71% of days) with a lack of satisfactory control of bowel urgency. RESULTS Patients had severe chronic IBS symptoms, and 89% of patients had D-IBS. Alosetron resulted in a greater percentage of days with satisfactory control of urgency compared with placebo (69% vs. 56%, respectively, P < 0.001). Greater percentages of alosetron-treated patients were GIS responders at 4, 8, and 12 weeks compared with placebo (59% vs. 41%, 63% vs. 41%, and 68% vs. 46%, respectively, P < 0.001). Patients with more frequent urgency had similar results. Constipation occurred in 28% and 9% of subjects in the alosetron- and placebo-treated groups, respectively. No cases of ischemic colitis were reported. CONCLUSIONS Alosetron effectively manages bowel urgency and improves global symptoms in women with severe chronic D-IBS.

Validation of Irritable Bowel Syndrome Global Improvement Scale: An Integrated Symptom End Point for Assessing Treatment Efficacy

The Global Improvement Scale (GIS) assesses multiple irritable bowel syndrome (IBS) symptoms using a patient-defined 7-point Likert scale ranging from symptoms substantially worse to substantially improved. To evaluate the scale as an efficacy end point, data were collected from two 12-week randomized, double-blind, placebo-controlled studies of female nonconstipated IBS patients. GIS responders were defined as having substantial or moderate improvement in IBS symptoms. GIS responders had more days with satisfactory control of urgency, firmer stools, fewer stools per day, and fewer days with incomplete evacuation compared to nonresponders. Substantially more GIS responders (90% and 89% in studies 1 and 2, respectively) were satisfied or very satisfied with their treatment overall compared to nonresponders (13% and 11%) ( r = 0.8 in both studies). GIS responders had greater satisfaction with medication relief of pain and discomfort and the time needed to return to usual activities. Favorable correlations between GIS and work and nonwork productivity losses were observed. Correlation of the GIS measure with IBS clinical end points establishes the validity of the GIS for measuring improvement in IBS symptoms. The GIS may be useful in assessing the efficacy of IBS interventions in future clinical trials.

Women with irritable bowel syndrome: differences in patients' and physicians' perceptions.

The effective management of irritable bowel syndrome (IBS) is enhanced by a therapeutic relationship between healthcare providers and the patient. This survey focused on addressing the symptoms and impact of IBS in women, as well as physician perceptions regarding IBS. A national survey was undertaken to 1) describe the attitudes, knowledge, treatment strategies, and compliance of women with IBS; 2) compare women with IBS to those without IBS on general health and activity limitations; 3) compare women with IBS to physicians regarding their relative perceptions about the disorder; and 4) determine whether physician gender influenced patient satisfaction.

Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE:The efficacy and tolerability of alosetron in women with diarrhea-predominant irritable bowel syndrome (IBS) have been established in double-blind, placebo-controlled trials. However, the degree to which alosetron fulfills the needs of those suffering from IBS has not been thoroughly examined from the patients perspective. This randomized, double-blind, placebo-controlled study conducted in women with diarrhea-predominant IBS evaluated patients’ overall satisfaction with treatment as well as their satisfaction with respect to several specific medication attributes.METHODS:Patients randomized to receive either alosetron 1 mg b.i.d. (n = 532) or placebo (n = 269) were administered a questionnaire on which they rated on 7-point Likert scales their prestudy IBS treatment (at the screening visit) or study medication (on wk 12 or final study visit) with respect to overall satisfaction and 11 specific medication attributes.RESULTS:Whereas approximately 10% of patients were satisfied or very satisfied overall with prestudy IBS medication, 69% of patients were satisfied or very satisfied overall with alosetron and 46% with placebo (p < 0.001) at the end of 12 wk of therapy. The majority of alosetron-treated patients (61–87%) were satisfied or very satisfied with each of 11 specific medication attributes (p < 0.001 vs placebo for each attribute). Favorable satisfaction ratings for alosetron were assigned to the five medication attributes that patients considered to be most important, including relief of urgency (68% alosetron vs 41% placebo), speed of relief (71% vs 40%), time to return to normal activities (75% vs 49%), relief of abdominal pain (62% vs 44%), and prevention of return of urgency (68% vs 42%).CONCLUSIONS:Women with diarrhea-predominant IBS are satisfied with alosetron 1 mg b.i.d. treatment overall and also with respect to specific attributes of IBS medication they consider most important.

Irritable bowel syndrome. A survey of nurses' knowledge.

Nurses in a variety of clinical settings are often involved in educating and managing patients with irritable bowel syndrome, though their knowledge and perceptions of irritable bowel syndrome are not well known. A national survey was undertaken as a part of a larger study of patients and healthcare providers to determine nurses’ knowledge of irritable bowel syndrome, including diagnosis, etiology, disease impact, management, beliefs, and attitudes regarding irritable bowel syndrome. In addition, the nurses’ perceptions of the effect of irritable bowel syndrome on the patient’s lifestyle and the severity of symptoms were compared to those of irritable bowel syndrome patients. One hundred practicing registered nurses were randomly selected and then interviewed by telephone using a questionnaire. A random-digit dialing method was used to identify and recruit 1,014 women with irritable bowel syndrome. The majority of registered nurses interviewed (75%) felt that nurses played a moderate-to-major role in counseling patients with irritable bowel syndrome. Only 13%, however, were aware of the diagnostic criteria for irritable bowel syndrome. The majority of nurse subjects felt the current therapies for irritable bowel syndrome had limited effectiveness varying from 6–21% depending on the symptom being treated. Almost half of the nurses felt they had an important role in management of irritable bowel syndrome and that both they and their patients needed more education about irritable bowel syndrome. There was close agreement between the nurses and the patients with regard to the impact of irritable bowel syndrome. With increased public attention on irritable bowel syndrome as a common problem affecting women, there is a need for nurses working in a variety of settings to have increased knowledge regarding the syndrome. In this article, recommendations are made regarding how to increase nurses’ knowledge about this common health problem.

Impact of Lotronex® (Alosetron HCL) on workplace productivity and activity time in females with non-constipated irritable bowel syndrome (IBS)

Impact of Lotronex® (Alosetron HCL) on workplace productivity and activity time in females with non-constipated irritable bowel syndrome (IBS)

IBS prevalence: results from a community based patient registry based on the Rome II criteria

IBS prevalence: results from a community based patient registry based on the Rome II criteria

Satisfactory control of bowel urgency and global improvement in irritable bowel syndrome (IBS) with Lotronex® (Alosetron HCl) therapy

Purpose: Bowel urgency is one of the most bothersome symptoms for subjects with nonconstipated IBS, affecting subjects on over 70% of days. This study screened for subjects with bowel urgency and compared treatment with Lotronex to placebo. Furthermore, the impact on global improvement of IBS symptoms and the relationship between global improvement and satisfactory control of urgency was evaluated.