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Mo1281 Optimal Dose of Ramosetron in Female Patients With Irritable Bowel Syndrome With Diarrhea: A Randomized, Placebo-Controlled Phase II Trial
treatment effect was similar to that observed in 2 previous double-blind, placebo controlled studies (TARGET 1 and 2) employing a single, 2-week course of treatment. Of the 1074 responders, 382 (36%) who entered the subsequent maintenance phase (18 weeks total) did not ever experience relapse. Of the 692 patients who relapsed, 636 were randomized to double-blind repeat treatment with RFX or placebo. In these patients, the mean time (±SD) to recurrence of symptoms was 11.9 (4.4) weeks (Figure 2). Interestingly, the majority of patients who did relapse based on severity of symptoms described only a partial recurrence of symptoms, with loss of response for either AP or SC components. Conclusions: In subjects responding to a single, 2-week course of rifaximin 550 mg TID, 36% did not relapse when followed for up to 18 additional weeks. Subjects who relapsed tended to exhibit symptom recurrence for either abdominal pain or stool consistency at a mean of approximately 3 months.
Mo1281
Background & Aims: Previous studies showed that 5 μg of a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist ramosetron is effective only in male patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D). We hypothesized that ramosetron is also effective in female patients with IBS-D but that the optimal dose in women is different from that in men. Methods: This randomized, double-blind, placebo-controlled, phase II dosefinding trial included 409 female outpatients with IBS-D treated in Japan. They were orally administered placebo (n = 102), 1.25 μg (n = 104), 2.5 μg (n = 104), or 5 μg (n = 99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rate of global improvement of IBS symptoms in the first month. Main secondary endpoints included monthly responder rate of global improvement of IBS symptoms in the second, third month, and last point as well as monthly responder rate of improvement of abdominal pain or discomfort, weekly mean changes in Bristol Stool Form Scale, and IBS-QOL. Results: The monthly responder rates of global improvement of IBS symptoms at the first month were 28.4% (95% CI, 19.9-38.2) in the placebo group, 39.4% (30.0-49.5) in the 1.25 μg of ramosetron group, 38.5% (29.1-48.5) in the 2.5 μg of ramosetron group, and 40.4% (30.7-50.7) in the 5 μg of ramosetron group (Shirley-Williams test, one-sided, α = 0.025, p = 0.048). Among the groups, the monthly responder rates of global improvement of IBS symptoms at the second month, third month, and last point were highest in the 2.5 μg of ramosetron group. Monthly responder rates of improvement of abdominal pain or discomfort at the second month (p = 0.002), third month (p = 0.005), and last point (p = 0.002) in the 2.5 μg of ramosetron group were significantly higher than those in the placebo group (χ2 test, two-sided, α = 0.05). Weekly mean changes in Bristol Stool Form Scale in the 2.5 μg or 5 μg of ramosetron group were significantly greater than those in the placebo group (p < 0.05) except at the 8th week of 2.5 μg. IBS-QOL did not change. Constipation was reported to have occurred in 5.9% of the patients in the placebo group, 12.5% of the patients in the 1.25 μg ramosetron group, 11.5% of the patients in the 2.5 μg ramosetron group, and 25.3% of the patients in the 5 μg ramosetron group. Conclusions: The study suggested that 2.5 μg of ramosetron is most effective and least harmful for treatment of female patients with IBS-D. The optimal dose of ramosetron for women is lower than that for men (Clinicaltrials.gov ID: NCT01274000).
Figure 1. Study flow
Mo1282 Attachment Styles in Patients With Irritable Bowel Syndrome (IBS), and Their Relationship With IBS Severity and Subtypes Carolina Bolino, Daria Piacentino, Horacio Vázquez, Monica Agdamus, Marcos Asade, Marina Furia, Lucila Facio, Ines Delli Quadri, Yen Ya Lien, Enrico Corazziari, Guido Iantorno Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder that negatively affects the quality of life. The social sphere is one of the most affected areas as the severity of symptoms of a stigmatized condition leads to social isolation and conflicts with others. Interpersonal relationships, additionally, can be a source of stress or an emotional support, with the consequent impact on the disease. Attachment paradigm is based on the concept that the loss of selective and stable bonding is detrimental to the maintenance of well-being. Little is known about the relationship between attachment styles and IBS, IBS severity and subtypes. Objectives: A)To describe and compare attachment styles in a group of IBS patients and healthy volunteers (HV). B) To evaluate if there is any association between the severity of IBS symptoms, IBS subtypes and IBS attachment styles. Materials and Methods: IBS patients and HV, all >18 years, were consecutively included. Major depression, delusional disorders, psychosis and /or treatment with antipsychotics were exclusion criteria. The study, with its cross-sectional and comparative design, was developed in the motility lab and mental health service of the Gastroenterology Hospital, in Buenos Aires, between June 2013 and November 2014. The severity of IBS symptoms questionnaire (IBS-SSS) and the interpersonal relationships questionnaire (ECRS) validated into Spanish were administered. Ethics: the protocol was approved by the local IRB. Statistical analysis: VCCSTAT 2.0. Medcalc 11.06., 95%CI; X2 test. Results: We included 50 patients and 20 HV. The demographic characteristics of the sample are described in the table. Education and offpring were different between groups (p<0.05). The main IBS subtypes were IBS-C and IBS-U, 36% each, followed by IBS-D 16% and IBS-M 12%. Most patients experienced moderate 42% (21/50) and severe 38% (19/50) symptoms. No relationship between age, subtypes and severity of symptoms was observed, however, moderate symptoms were predominant in women (p<0.05). A) Patients' attachment styles were: 36% (95%CI 23-50; 18/50) preoccupied, 34% (95%CI 21-48; 17/50) fearful-avoidant, 22% (95%CI 12-36; 11/50) secure, 8% (95%CI 2.2-19; 4/50) dismissive-avoidant. Fearful and secure attachment styles were more prevalent in patients and HV, respectively (p<0.05). B) No association between age, gender, subtypes, symptom severity and attachment styles was observed (p=ns). Conclusions: The predominant attachment styles were fearful in IBS patients and secure in HV. No relationship between age, gender, IBS subtypes and severity of symptoms and attachment styles was observed. Such findings suggest that attachment styles should be considered in the clinical management of IBS patients. Demographic characteristics of the sample
Figure 2. Survival function in open-label responders who relapsed and were randomized to double-blind repeat treatment (n=636) Mo1280 Effect of Ramosetron in Female Patients With Irritable Bowel Syndrome With Diarrhea: Phase III Long-Term Study Shin Fukudo, Yoshikazu Kinoshita, Toshikatsu Okumura, Motoko Ida, Kenta Hayashi, Hiraku Akiho, Yoshihiro Nakashima, Ken Haruma Background & Aims: Serious side effects like ischemic colitis have been reported in female patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D) treated with a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist alosetron. In contrast, no case in 901 IBS-D patients who were given ramosetron had ischemic colitis. However, the long-term safety of administration of ramosetron to female patients with IBS-D is unknown. The aim of this study was to assess the long-term safety of ramosetron for treatment of female patients with IBS-D. Methods: This was a phase III, non-blinded, long-term safety (LTS) trial for the treatment of Japanese female patients with IBS-D diagnosed with Rome III criteria. A total of 202 patients gave informed consent, but 51 were mainly excluded based on exclusion criteria. The remaining 151 patients were given 2.5 μg of ramosetron for 4 weeks and responders (n = 132) continued the same dose for another 48 weeks. Non-responders at 4 weeks (n = 19) were given 5 μg of ramosetron for 48 weeks. After week 52, 106 cases with 2.5 μg and 17 cases with 5 μg completed the study. Efficacy was evaluated by monthly responder rates with global improvement (0: completely relieved, 1: considerably relieved, 2: somewhat relieved, 3: unchanged, and 4: worsened) of overall IBS symptoms, improvement in stool consistency, improvement of abdominal pain and discomfort, Bristol Stool Form Scale, and IBS-QOL. Results: Ramosetron-treated patients showed high responder rates of global improvement [68.7% (95% CI, 60.0-76.5) with 2.5 μg, 84.2% (60.4-96.6) with 5 μg]. Stool consistency, abdominal pain and discomfort, and Bristol Stool Form Scale improved significantly at week 52. Changes in IBS-QOL at the last point were 20.7 (17.9-23.5) with 2.5 μg of ramosetron and 21.3 (14.2-28.4) with 5 μg of ramosetron. Concerning safety, no serious adverse event related to ramosetron, in particular ischemic colitis, was observed in patients with either dose. However, constipation occurred in 19.7% in patients given 2.5 μg of ramosetron and 10.5% in patients given 5 μg of ramosetron. Conclusions: The results suggest that 2.5 μg and 5 μg of ramosetron for female patients with IBS-D show long-term efficacy and safety. Clinicians should be aware that 1/5 of women with IBS-D receiving ramosetron may suffer from constipation during treatment (Clinicaltrials.gov ID: NCT01736423).
S-659
AGA Abstracts
AGA Abstracts
Optimal Dose of Ramosetron in Female Patients With Irritable Bowel Syndrome With Diarrhea: A Randomized, Placebo-Controlled Phase II Trial Shin Fukudo, Kei Matsueda, Ken Haruma, Motoko Ida, Hisatake Hayase, Hiraku Akiho, Yoshihiro Nakashima, Michio Hongo
Mo1281
Background & Aims: Previous studies showed that 5 μg of a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist ramosetron is effective only in male patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D). We hypothesized that ramosetron is also effective in female patients with IBS-D but that the optimal dose in women is different from that in men. Methods: This randomized, double-blind, placebo-controlled, phase II dosefinding trial included 409 female outpatients with IBS-D treated in Japan. They were orally administered placebo (n = 102), 1.25 μg (n = 104), 2.5 μg (n = 104), or 5 μg (n = 99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rate of global improvement of IBS symptoms in the first month. Main secondary endpoints included monthly responder rate of global improvement of IBS symptoms in the second, third month, and last point as well as monthly responder rate of improvement of abdominal pain or discomfort, weekly mean changes in Bristol Stool Form Scale, and IBS-QOL. Results: The monthly responder rates of global improvement of IBS symptoms at the first month were 28.4% (95% CI, 19.9-38.2) in the placebo group, 39.4% (30.0-49.5) in the 1.25 μg of ramosetron group, 38.5% (29.1-48.5) in the 2.5 μg of ramosetron group, and 40.4% (30.7-50.7) in the 5 μg of ramosetron group (Shirley-Williams test, one-sided, α = 0.025, p = 0.048). Among the groups, the monthly responder rates of global improvement of IBS symptoms at the second month, third month, and last point were highest in the 2.5 μg of ramosetron group. Monthly responder rates of improvement of abdominal pain or discomfort at the second month (p = 0.002), third month (p = 0.005), and last point (p = 0.002) in the 2.5 μg of ramosetron group were significantly higher than those in the placebo group (χ2 test, two-sided, α = 0.05). Weekly mean changes in Bristol Stool Form Scale in the 2.5 μg or 5 μg of ramosetron group were significantly greater than those in the placebo group (p < 0.05) except at the 8th week of 2.5 μg. IBS-QOL did not change. Constipation was reported to have occurred in 5.9% of the patients in the placebo group, 12.5% of the patients in the 1.25 μg ramosetron group, 11.5% of the patients in the 2.5 μg ramosetron group, and 25.3% of the patients in the 5 μg ramosetron group. Conclusions: The study suggested that 2.5 μg of ramosetron is most effective and least harmful for treatment of female patients with IBS-D. The optimal dose of ramosetron for women is lower than that for men (Clinicaltrials.gov ID: NCT01274000).
Figure 1. Study flow
Mo1282 Attachment Styles in Patients With Irritable Bowel Syndrome (IBS), and Their Relationship With IBS Severity and Subtypes Carolina Bolino, Daria Piacentino, Horacio Vázquez, Monica Agdamus, Marcos Asade, Marina Furia, Lucila Facio, Ines Delli Quadri, Yen Ya Lien, Enrico Corazziari, Guido Iantorno Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder that negatively affects the quality of life. The social sphere is one of the most affected areas as the severity of symptoms of a stigmatized condition leads to social isolation and conflicts with others. Interpersonal relationships, additionally, can be a source of stress or an emotional support, with the consequent impact on the disease. Attachment paradigm is based on the concept that the loss of selective and stable bonding is detrimental to the maintenance of well-being. Little is known about the relationship between attachment styles and IBS, IBS severity and subtypes. Objectives: A)To describe and compare attachment styles in a group of IBS patients and healthy volunteers (HV). B) To evaluate if there is any association between the severity of IBS symptoms, IBS subtypes and IBS attachment styles. Materials and Methods: IBS patients and HV, all >18 years, were consecutively included. Major depression, delusional disorders, psychosis and /or treatment with antipsychotics were exclusion criteria. The study, with its cross-sectional and comparative design, was developed in the motility lab and mental health service of the Gastroenterology Hospital, in Buenos Aires, between June 2013 and November 2014. The severity of IBS symptoms questionnaire (IBS-SSS) and the interpersonal relationships questionnaire (ECRS) validated into Spanish were administered. Ethics: the protocol was approved by the local IRB. Statistical analysis: VCCSTAT 2.0. Medcalc 11.06., 95%CI; X2 test. Results: We included 50 patients and 20 HV. The demographic characteristics of the sample are described in the table. Education and offpring were different between groups (p<0.05). The main IBS subtypes were IBS-C and IBS-U, 36% each, followed by IBS-D 16% and IBS-M 12%. Most patients experienced moderate 42% (21/50) and severe 38% (19/50) symptoms. No relationship between age, subtypes and severity of symptoms was observed, however, moderate symptoms were predominant in women (p<0.05). A) Patients' attachment styles were: 36% (95%CI 23-50; 18/50) preoccupied, 34% (95%CI 21-48; 17/50) fearful-avoidant, 22% (95%CI 12-36; 11/50) secure, 8% (95%CI 2.2-19; 4/50) dismissive-avoidant. Fearful and secure attachment styles were more prevalent in patients and HV, respectively (p<0.05). B) No association between age, gender, subtypes, symptom severity and attachment styles was observed (p=ns). Conclusions: The predominant attachment styles were fearful in IBS patients and secure in HV. No relationship between age, gender, IBS subtypes and severity of symptoms and attachment styles was observed. Such findings suggest that attachment styles should be considered in the clinical management of IBS patients. Demographic characteristics of the sample
Figure 2. Survival function in open-label responders who relapsed and were randomized to double-blind repeat treatment (n=636) Mo1280 Effect of Ramosetron in Female Patients With Irritable Bowel Syndrome With Diarrhea: Phase III Long-Term Study Shin Fukudo, Yoshikazu Kinoshita, Toshikatsu Okumura, Motoko Ida, Kenta Hayashi, Hiraku Akiho, Yoshihiro Nakashima, Ken Haruma Background & Aims: Serious side effects like ischemic colitis have been reported in female patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D) treated with a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist alosetron. In contrast, no case in 901 IBS-D patients who were given ramosetron had ischemic colitis. However, the long-term safety of administration of ramosetron to female patients with IBS-D is unknown. The aim of this study was to assess the long-term safety of ramosetron for treatment of female patients with IBS-D. Methods: This was a phase III, non-blinded, long-term safety (LTS) trial for the treatment of Japanese female patients with IBS-D diagnosed with Rome III criteria. A total of 202 patients gave informed consent, but 51 were mainly excluded based on exclusion criteria. The remaining 151 patients were given 2.5 μg of ramosetron for 4 weeks and responders (n = 132) continued the same dose for another 48 weeks. Non-responders at 4 weeks (n = 19) were given 5 μg of ramosetron for 48 weeks. After week 52, 106 cases with 2.5 μg and 17 cases with 5 μg completed the study. Efficacy was evaluated by monthly responder rates with global improvement (0: completely relieved, 1: considerably relieved, 2: somewhat relieved, 3: unchanged, and 4: worsened) of overall IBS symptoms, improvement in stool consistency, improvement of abdominal pain and discomfort, Bristol Stool Form Scale, and IBS-QOL. Results: Ramosetron-treated patients showed high responder rates of global improvement [68.7% (95% CI, 60.0-76.5) with 2.5 μg, 84.2% (60.4-96.6) with 5 μg]. Stool consistency, abdominal pain and discomfort, and Bristol Stool Form Scale improved significantly at week 52. Changes in IBS-QOL at the last point were 20.7 (17.9-23.5) with 2.5 μg of ramosetron and 21.3 (14.2-28.4) with 5 μg of ramosetron. Concerning safety, no serious adverse event related to ramosetron, in particular ischemic colitis, was observed in patients with either dose. However, constipation occurred in 19.7% in patients given 2.5 μg of ramosetron and 10.5% in patients given 5 μg of ramosetron. Conclusions: The results suggest that 2.5 μg and 5 μg of ramosetron for female patients with IBS-D show long-term efficacy and safety. Clinicians should be aware that 1/5 of women with IBS-D receiving ramosetron may suffer from constipation during treatment (Clinicaltrials.gov ID: NCT01736423).
S-659
AGA Abstracts
AGA Abstracts
Optimal Dose of Ramosetron in Female Patients With Irritable Bowel Syndrome With Diarrhea: A Randomized, Placebo-Controlled Phase II Trial Shin Fukudo, Kei Matsueda, Ken Haruma, Motoko Ida, Hisatake Hayase, Hiraku Akiho, Yoshihiro Nakashima, Michio Hongo