- Email: [email protected]
Mo1279 Durability of Benefit in IBS-D Patients Responding to a 2-Week Course of Rifaximin: Results From TARGET 3
Questionnaire), and general HRQOL (SF-36)]. GI symptoms were assessed using the GI Symptom Rating Scale for IBS (GSRS), and IBS-related HRQOL using the BEST questionnaire. Physician assessment of IBS symptom severity was documented using an established 4-point Likert scale (0= no symptoms, 3= disabling symptoms). Prescription of an opioid (agent, dose) was documented at initial presentation. Results: A current opioid was reported by 59 (43.1%) of IBS patients. Controlling for age and sex, opioid use was significantly related to depression (OR 2.9, 95%CI 1.3-6.8, p=0.01), anxiety (OR 3.0, 95%CI 1.3-6.9, p=0.003), and high somatization (OR 3.0, 95%CI 1.3-6.6, p=0.009). (Need to mention how many had a history of abuse here). 30 (50.8%) IBS patients with a history of abuse were on opioids, compared to 26/78 (33.3%) without abuse histories (X2=4.3, p=0.039). Despite their intended analgesic benefits, IBS patients with opioid prescriptions reported worse GI symptom severity (GSRS total: 49.0±2.3 vs 42.5±1.8, p=0.034) GI HRQOL (BEST: 103.1±33.5 vs 50.1±3.7, p=0.026) and poorer general HRQOL (50.6±2.7 vs 35.6±3.2, p<0.001). Despite patient perceptions, physician assessment of IBS symptom severity was comparable across participants, independent of opioid use (p=0.35). Conclusion: Prescription opioid use is prevalent among IBS patients, and is strongly associated with psychiatric comorbidity and history of abuse. IBS patients using prescription opioids report more severe GI symptoms, as well as poorer IBS related and general HRQOL despite physician perceptions of their clinical status. Understanding the cause-effect relationship of these observations will be paramount to the successful reduction of opioid prescriptions in FGID patients.
AGA Abstracts
Most common adverse events during double-blind phase (>3% of subjects)
Mo1278 Review of Systems and Medication Allergies Predict Presence and Severity of Functional GI Disorders (FGIDs) Pratibha Abraham, Navya D. Kanuri, Benjamin Cassell, Britt M. Gott, Billy D. Nix, C. Prakash Gyawali, Gregory S. Sayuk Figure. Study flow
Background: Functional GI disorder (FGID) manifest clinically-unexplained symptoms with an abdominal pain predominance. FGID patients have higher numbers of non-GI functional syndromes, recent somatic symptoms, and greater psychiatric comorbidity compared to non-FGID controls (Sayuk et al Clin Gastro Hep 2007). Previously it has been demonstrated that simple review of systems (ROS) checklists have predictive value in establishing FGID diagnoses (Brown JH et al J Clin Gastro 2003). FGID patients may report higher numbers of medication allergies/intolerances as part of hypersensitivity; thus this factor may serve as an additional clinical clue to FGID diagnoses. This study was conducted to assess the relationship of medication intolerances and ROS with FGID symptom severity and GI healthrelated quality of life (HRQOL). We also sought to evaluate the association of ROS and allergy reports with psychiatric comorbidity (anxiety, depression, somatization). Methods: 208 patients (156 F, 49.9±1.2 yrs) seen in a tertiary GI setting from 8/2009-5/2014 completed self-reports of ROS (51 symptoms without GI symptoms/79 with GI symptoms) and medication allergies. Validated instruments assessed mood (Beck Depression/Anxiety Inventories), somatization (PHQ-12), and general HRQOL (SF-36). GI symptoms were assessed using the GI Symptom Rating Scale (GSRS) and the B.E.S.T. questionnaire measured bowel-related HRQOL. ROME III Research Diagnostic Questions confirmed FGID diagnoses (FD and/or IBS). Results: 153 (73.6%) patients met ROME criteria for at least one FGID (110FD, 128 IBS). Compared to non-FGID GI patients, FGID subjects had twice the number of positive ROS (14.1±0.9 vs 7.0±0.8, p=0.019) but similar mean numbers of medication allergies (1.3±0.2 vs 1.0±0.2, p=0.36). Patients endorsing more than 7 ROS had a three-fold higher likelihood of a FGID diagnosis (OR 3.4, 95%CI 1.8-6.4, p<0.001). ROS correlated with depression, anxiety, and somatization (r=0.5-0.7, p<0.001 for each). ROS remained as an independent predictor of FGID in multivariate regression analysis with all psychiatric measures included (p=0.023). Controlling for age and sex, greater numbers of ROS and medication allergies both significantly predicted higher GSRS (B=0.53, p=0.002; B=3.6, p= 0.003,respectively). Only ROS predicted poorer GI HRQOL (B=0.92, p=0.004) and general HRQOL (B=-1.4, p<0.001). Conclusion: High numbers of endorsed symptoms on selfreport ROS checklists predict FGID diagnoses, and along with medication allergies are associated with more severe GI symptoms. ROS also strongly correlate with psychiatric measures; when present in high numbers, ROS and medication allergies should raise clinical suspicion of the hypersensitivity common to FGIDs.
Mo1276 Abuse Histories Predict Greater Functional GI and Pain Comorbidities in Irritable Bowel Syndrome (IBS) Patients Navya D. Kanuri, Pratibha Abraham, Steven E. Bruce, Kamila S. White, Benjamin Cassell, Britt M. Gott, Billy D. Nix, C. Prakash Gyawali, Gregory S. Sayuk Background: IBS is a common functional GI syndrome with a prominent pain component. History of physical, sexual, and/or emotional abuse is more prevalent among IBS sufferers. Previously we reported that abuse is linked to more severe and frequent IBS symptoms and poorer health related quality of life (HRQOL). If abuse experiences heighten brain neurocircuitry sensitivity to pain experiences as has been suggested (Ringel Y et al Gastroenterol 2008), this study then sought to examine the effects of an abuse history on rates of functional GI disorder (FGID) diagnoses, non-GI diagnoses, and recent pain symptoms among an IBS population; further, we aimed to determine whether experiences of multiple forms of abuse resulted in greater likelihood of developing functional GI and non-GI complaints. Methods: Consecutive GI outpatients were invited to complete ROME III Research Diagnostic Questionnaire to establish FGID criteria. Self-report questionnaires on abuse history (Life-Stress Questionnaire) were obtained, with a focus on physical, sexual, and emotional abuse. IBS patients with histories of any form of these abuse experiences were defined as IBS+/Abuse+. Recent non-GI somatic symptoms (PHQ-12), and historical somatic pain diagnoses (e.g., fibromyalgia, headache, chronic back pain) were recorded. 272 ROMEdefined IBS subjects (50.1±0.9 yrs, 81% female) were identified, and reported greater rates of abuse compared to a non-IBS comparator group (n=246): physical (18.1% vs 6.6%), sexual (15.5% vs 7.4%), and emotional (31.7% vs 16.9%) (p<0.005 for each). Results: In total, n=95 (34.9%) IBS subjects reported at least one form of abuse (IBS+/Abuse+), and n= 54 (19.8%) reported experiencing >1 form of abuse. Compared to IBS subjects without abuse histories (IBS+/Abuse-), IBS+/Abuse+ subjects had greater total numbers of ROME diagnoses (2.5±0.3 vs 2.1±0.3, p=0.10), non-GI pain diagnoses (1.9±0.2 vs. 0.9±0.08, p<0.001), and more recent somatic symptoms (9.6±0.5 vs. 7.7±0.4, p=0.001). All forms of abuse experiences imposed similar risk of functional syndromes. An additive effect of multiple forms of abuse was observed, such that greater numbers non-GI pain disorders (F=13.5, p<0.001) and somatic symptom complaints (F=5.8, p=0.001) were noted with the experience of multiple forms of abuse. This additive effect was not relevant to the number of ROME diagnoses recorded, however (F=0.69, p=0.55). Conclusions: Abuse experiences common in IBS patients are associated with reports of greater non-GI symptoms, historical somatic diagnoses, and to a lesser extent additional FGID diagnoses in IBS patients; these relationships are particularly robust when multiple forms of abuse have been experienced. These observations provide indirect evidence of an enhanced susceptibility to both GI and somatic functional disorders following abuse.
Mo1279 Durability of Benefit in IBS-D Patients Responding to a 2-Week Course of Rifaximin: Results From TARGET 3 Mark Pimentel, Lin Chang, Anthony Lembo, Andrew C. Barrett, Jing Yu, Enoch Bortey, Craig Paterson, William P. Forbes Background: Rifaximin (RFX) has demonstrated efficacy in the treatment of IBS-D symptoms in 2 large, randomized, controlled trials of 12 weeks duration following a single 2-week treatment. Current evidence suggests that the durability of effect may persist beyond the 12 weeks evaluated in the pivotal studies. The objective of this analysis was to more accurately characterize the duration of benefit in patients who respond to an initial course of rifaximin therapy. Methods: Patients with IBS-D (Rome III criteria) with average symptom severity scores of ≥ 3 for IBS-related abdominal pain (AP, scale 0-10) and bloating (scale 0-6), with ≥ 2 stools with Bristol Stool Scale (BSS) Type 6 (loose) or 7 (watery) during the 7-day baseline were entered into the open-label phase (OL) of the trial (Figure 1). In OL, all patients were treated with RFX 550 mg TID for 2 weeks, followed by a 4-week treatmentfree follow-up period to assess response to treatment. A responder was defined as meeting weekly response criteria for both AP (≥30% decrease from baseline in mean weekly pain score) and stool consistency (SC) (≥50% decrease from baseline in number of days/week with BSS Type 6 or 7) for ≥2 of 4 weeks. Responders in the OL phase were subsequently followed until relapse (up to 18 additional weeks), upon which they were randomized to receive 2 double-blind, placebo-controlled, repeat treatments (RFX 550 mg TID or placebo) separated by 10 weeks. Relapse was defined as loss of response for either AP OR SC for ≥ 3 out of a 4 week period during the 18-week maintenance phase. Results: Of 2579 patients (mean age: 46.4; 68% female; mean daily bowel movements: 3.9; mean daily AP score: 5.5; mean daily SC score: 5.6) who received OL RFX, 2331 were evaluable for efficacy, of which 1074 (46%) were responders based on the composite endpoint of AP and SC. This initial
Mo1277 Clinical Factors Associated With Opioid Prescription Use Among Irritable Bowel Syndrome (IBS) Patients Navya D. Kanuri, Pratibha Abraham, Benjamin Cassell, Steven E. Bruce, Kamila S. White, Britt M. Gott, Billy D. Nix, C. Prakash Gyawali, Gregory S. Sayuk Background: Prescription of opioids for non-cancer pain indications is increasing dramatically in the US, without evidence for established benefit in many of these settings (Eriksen et al, Pain 2006). As chronic abdominal pain is a predominant symptom in IBS, this patient population may be particularly at risk for treatment with opioids (Rx). Opioids paradoxically may worsen IBS symptoms via alterations in intestinal transit, upregulation of pain pathways and development of narcotic bowel syndrome. We evaluated the relationship between opioid prescriptions and self-reported or physician assessed IBS symptoms in determining clinical and psychological factors associated with prescription opioid use in IBS patients. Methods: 137 clinically-diagnosed IBS patients (112 F, 49.9±1.2 yrs) seen in a tertiary GI setting over a 5 years completed questionnaires [mood (Beck Depression/Anxiety Inventories), somatization (PHQ-15), abuse history (physical, sexual, and/or emotional on Life-Stress
AGA Abstracts
S-658
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).
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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
AGA Abstracts
Most common adverse events during double-blind phase (>3% of subjects)
Mo1278 Review of Systems and Medication Allergies Predict Presence and Severity of Functional GI Disorders (FGIDs) Pratibha Abraham, Navya D. Kanuri, Benjamin Cassell, Britt M. Gott, Billy D. Nix, C. Prakash Gyawali, Gregory S. Sayuk Figure. Study flow
Background: Functional GI disorder (FGID) manifest clinically-unexplained symptoms with an abdominal pain predominance. FGID patients have higher numbers of non-GI functional syndromes, recent somatic symptoms, and greater psychiatric comorbidity compared to non-FGID controls (Sayuk et al Clin Gastro Hep 2007). Previously it has been demonstrated that simple review of systems (ROS) checklists have predictive value in establishing FGID diagnoses (Brown JH et al J Clin Gastro 2003). FGID patients may report higher numbers of medication allergies/intolerances as part of hypersensitivity; thus this factor may serve as an additional clinical clue to FGID diagnoses. This study was conducted to assess the relationship of medication intolerances and ROS with FGID symptom severity and GI healthrelated quality of life (HRQOL). We also sought to evaluate the association of ROS and allergy reports with psychiatric comorbidity (anxiety, depression, somatization). Methods: 208 patients (156 F, 49.9±1.2 yrs) seen in a tertiary GI setting from 8/2009-5/2014 completed self-reports of ROS (51 symptoms without GI symptoms/79 with GI symptoms) and medication allergies. Validated instruments assessed mood (Beck Depression/Anxiety Inventories), somatization (PHQ-12), and general HRQOL (SF-36). GI symptoms were assessed using the GI Symptom Rating Scale (GSRS) and the B.E.S.T. questionnaire measured bowel-related HRQOL. ROME III Research Diagnostic Questions confirmed FGID diagnoses (FD and/or IBS). Results: 153 (73.6%) patients met ROME criteria for at least one FGID (110FD, 128 IBS). Compared to non-FGID GI patients, FGID subjects had twice the number of positive ROS (14.1±0.9 vs 7.0±0.8, p=0.019) but similar mean numbers of medication allergies (1.3±0.2 vs 1.0±0.2, p=0.36). Patients endorsing more than 7 ROS had a three-fold higher likelihood of a FGID diagnosis (OR 3.4, 95%CI 1.8-6.4, p<0.001). ROS correlated with depression, anxiety, and somatization (r=0.5-0.7, p<0.001 for each). ROS remained as an independent predictor of FGID in multivariate regression analysis with all psychiatric measures included (p=0.023). Controlling for age and sex, greater numbers of ROS and medication allergies both significantly predicted higher GSRS (B=0.53, p=0.002; B=3.6, p= 0.003,respectively). Only ROS predicted poorer GI HRQOL (B=0.92, p=0.004) and general HRQOL (B=-1.4, p<0.001). Conclusion: High numbers of endorsed symptoms on selfreport ROS checklists predict FGID diagnoses, and along with medication allergies are associated with more severe GI symptoms. ROS also strongly correlate with psychiatric measures; when present in high numbers, ROS and medication allergies should raise clinical suspicion of the hypersensitivity common to FGIDs.
Mo1276 Abuse Histories Predict Greater Functional GI and Pain Comorbidities in Irritable Bowel Syndrome (IBS) Patients Navya D. Kanuri, Pratibha Abraham, Steven E. Bruce, Kamila S. White, Benjamin Cassell, Britt M. Gott, Billy D. Nix, C. Prakash Gyawali, Gregory S. Sayuk Background: IBS is a common functional GI syndrome with a prominent pain component. History of physical, sexual, and/or emotional abuse is more prevalent among IBS sufferers. Previously we reported that abuse is linked to more severe and frequent IBS symptoms and poorer health related quality of life (HRQOL). If abuse experiences heighten brain neurocircuitry sensitivity to pain experiences as has been suggested (Ringel Y et al Gastroenterol 2008), this study then sought to examine the effects of an abuse history on rates of functional GI disorder (FGID) diagnoses, non-GI diagnoses, and recent pain symptoms among an IBS population; further, we aimed to determine whether experiences of multiple forms of abuse resulted in greater likelihood of developing functional GI and non-GI complaints. Methods: Consecutive GI outpatients were invited to complete ROME III Research Diagnostic Questionnaire to establish FGID criteria. Self-report questionnaires on abuse history (Life-Stress Questionnaire) were obtained, with a focus on physical, sexual, and emotional abuse. IBS patients with histories of any form of these abuse experiences were defined as IBS+/Abuse+. Recent non-GI somatic symptoms (PHQ-12), and historical somatic pain diagnoses (e.g., fibromyalgia, headache, chronic back pain) were recorded. 272 ROMEdefined IBS subjects (50.1±0.9 yrs, 81% female) were identified, and reported greater rates of abuse compared to a non-IBS comparator group (n=246): physical (18.1% vs 6.6%), sexual (15.5% vs 7.4%), and emotional (31.7% vs 16.9%) (p<0.005 for each). Results: In total, n=95 (34.9%) IBS subjects reported at least one form of abuse (IBS+/Abuse+), and n= 54 (19.8%) reported experiencing >1 form of abuse. Compared to IBS subjects without abuse histories (IBS+/Abuse-), IBS+/Abuse+ subjects had greater total numbers of ROME diagnoses (2.5±0.3 vs 2.1±0.3, p=0.10), non-GI pain diagnoses (1.9±0.2 vs. 0.9±0.08, p<0.001), and more recent somatic symptoms (9.6±0.5 vs. 7.7±0.4, p=0.001). All forms of abuse experiences imposed similar risk of functional syndromes. An additive effect of multiple forms of abuse was observed, such that greater numbers non-GI pain disorders (F=13.5, p<0.001) and somatic symptom complaints (F=5.8, p=0.001) were noted with the experience of multiple forms of abuse. This additive effect was not relevant to the number of ROME diagnoses recorded, however (F=0.69, p=0.55). Conclusions: Abuse experiences common in IBS patients are associated with reports of greater non-GI symptoms, historical somatic diagnoses, and to a lesser extent additional FGID diagnoses in IBS patients; these relationships are particularly robust when multiple forms of abuse have been experienced. These observations provide indirect evidence of an enhanced susceptibility to both GI and somatic functional disorders following abuse.
Mo1279 Durability of Benefit in IBS-D Patients Responding to a 2-Week Course of Rifaximin: Results From TARGET 3 Mark Pimentel, Lin Chang, Anthony Lembo, Andrew C. Barrett, Jing Yu, Enoch Bortey, Craig Paterson, William P. Forbes Background: Rifaximin (RFX) has demonstrated efficacy in the treatment of IBS-D symptoms in 2 large, randomized, controlled trials of 12 weeks duration following a single 2-week treatment. Current evidence suggests that the durability of effect may persist beyond the 12 weeks evaluated in the pivotal studies. The objective of this analysis was to more accurately characterize the duration of benefit in patients who respond to an initial course of rifaximin therapy. Methods: Patients with IBS-D (Rome III criteria) with average symptom severity scores of ≥ 3 for IBS-related abdominal pain (AP, scale 0-10) and bloating (scale 0-6), with ≥ 2 stools with Bristol Stool Scale (BSS) Type 6 (loose) or 7 (watery) during the 7-day baseline were entered into the open-label phase (OL) of the trial (Figure 1). In OL, all patients were treated with RFX 550 mg TID for 2 weeks, followed by a 4-week treatmentfree follow-up period to assess response to treatment. A responder was defined as meeting weekly response criteria for both AP (≥30% decrease from baseline in mean weekly pain score) and stool consistency (SC) (≥50% decrease from baseline in number of days/week with BSS Type 6 or 7) for ≥2 of 4 weeks. Responders in the OL phase were subsequently followed until relapse (up to 18 additional weeks), upon which they were randomized to receive 2 double-blind, placebo-controlled, repeat treatments (RFX 550 mg TID or placebo) separated by 10 weeks. Relapse was defined as loss of response for either AP OR SC for ≥ 3 out of a 4 week period during the 18-week maintenance phase. Results: Of 2579 patients (mean age: 46.4; 68% female; mean daily bowel movements: 3.9; mean daily AP score: 5.5; mean daily SC score: 5.6) who received OL RFX, 2331 were evaluable for efficacy, of which 1074 (46%) were responders based on the composite endpoint of AP and SC. This initial
Mo1277 Clinical Factors Associated With Opioid Prescription Use Among Irritable Bowel Syndrome (IBS) Patients Navya D. Kanuri, Pratibha Abraham, Benjamin Cassell, Steven E. Bruce, Kamila S. White, Britt M. Gott, Billy D. Nix, C. Prakash Gyawali, Gregory S. Sayuk Background: Prescription of opioids for non-cancer pain indications is increasing dramatically in the US, without evidence for established benefit in many of these settings (Eriksen et al, Pain 2006). As chronic abdominal pain is a predominant symptom in IBS, this patient population may be particularly at risk for treatment with opioids (Rx). Opioids paradoxically may worsen IBS symptoms via alterations in intestinal transit, upregulation of pain pathways and development of narcotic bowel syndrome. We evaluated the relationship between opioid prescriptions and self-reported or physician assessed IBS symptoms in determining clinical and psychological factors associated with prescription opioid use in IBS patients. Methods: 137 clinically-diagnosed IBS patients (112 F, 49.9±1.2 yrs) seen in a tertiary GI setting over a 5 years completed questionnaires [mood (Beck Depression/Anxiety Inventories), somatization (PHQ-15), abuse history (physical, sexual, and/or emotional on Life-Stress
AGA Abstracts
S-658
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