Bowel Disease Patients In Remission Research Articles

Depression symptoms increase the risk for initiation or switching to biologic therapy in pediatric inflammatory bowel disease patients in remission

Background and aimsAnxiety and depression symptoms are common in IBD population, both adult and pediatric patients. Increased psychological distress might contribute to initiation and switching to biologic therapy in adult patients with IBD or other chronic inflammatory diseases. Aim of the present study are to evaluate anxiety and depression symptoms in IBD pediatric patients with disease remission and investigate their role in initiation or switching to biologic therapy.MethodsWe performed a retrospective analysis on IBD pediatric patients, assessing for anxiety (GAD-7) and depression (PHQ-9) symptoms. Demographic and disease characteristics were obtained from medical records.ResultsEighty-six patients [31 (36%) females - mean age = 15.6 (SD = 2.8) years] were included. Patients scored above cut-off (> 10) on PHQ-9 and GAD-7 were 17 (19.7%) and 18 (20.9%), respectively. No differences were found between UC and CD patients. Baseline clinically relevant depression symptoms were significantly associated with the odds of initiating or switching to biologic therapy within 2 years [OR = 4.5 (1.4–14.3)], even after confounders adjustment [4.2 (1.2–14.9)]. Relationship was not significant with anxiety symptoms.ConclusionAnxiety and depression symptoms is relatively common in pediatric IBD population, even with disease remission. Pediatric IBD patients with high depression symptoms are at increased risk of initiating or switching to biologic therapy. Mental health screening programs should be incorporated in routine clinical practice, especially for depression, regardless of disease activity and disease type. Early diagnosis and proper intervention for mental illness should be part of routine IBD management.

A Pilot Study of Clinical Evaluation and Formation Mechanism of Irritable Bowel Syndrome-like Symptoms in Inflammatory Bowel Disease Patients in Remission.

Background/AimsSome inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS.MethodsForty-seven patients with Crohn’s disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot.ResultsPrevalence of IBS-like symptoms in Crohn’s disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity.ConclusionIBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.

P793 Patients’ concerns are strongly associated with distress and quality of life among family caregivers of adult inflammatory bowel disease patients in remission

Abstract Background Patients’ concerns were negatively associated with adaptation and outcomes in inflammatory bowel diseases (IBD), even when the disease is in remission. Concurrently, relatives overestimate patients’ worries with unknown implications on their quality of life (QoL).Our aim was to investigate the association among disease-related concerns, distress and QoL among family caregivers of adult IBD patients in remission. Methods One hundred and ninety-three consecutive IBD patient-caregiver dyads from the outpatient clinic of two referral centres were screened for eligibility. Dyads with psychiatric and other co morbidities were excluded. 66 patients were in remission and recruited. Patients’ concerns and caregivers’ distress were assessed by using the Rating Form of IBD patient Concerns (RFIPC) and the caregiver self-assessment questionnaire ‘How Are You?’ of the American Medical Association, respectively, whereas caregiver’s QoL was measured with the SF-36 questionnaire. Data are presented as median and range. The influence of population characteristics and patients’ concerns on caregivers’ distress and QoL were evaluated with linear regression. Results Sixty-six IBD patients (40[47] years, 51.5 % females, 37.9% full-time employment) and caregivers (47[33] years, 60% females, 60% 1st degree relative, 60% full-time employed) included in the analysis. Among patients, the median RFIPC score was 36.8 [43.52], whereas worries about the unknown nature of the disease, feeling out of control, having access to quality medical care, the fear of side effects and the energy level prevailed. Among caregivers, a median of 7 [14] hours were spent on care giving per week with 48.4 % of the caregivers developing distress and achieving low scores on sf-36. Among all examined variables, the increased level of concerns was the sole factor that was independently associated with increased distress (beta=0.947, p = 0.000) and low QoL (beta=–0.567–0.345, p = 0.000) in the caregivers’ population. Conclusion In remission, increased patients’ concerns was the only factor that was found to be strongly associated with increased level of distress and low QoL in family caregivers. Potential interventions might seek to provide support to those who care for IBD patients. References

Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity.

Background & AimsDespite achieving endoscopic remission, more than 20% of inflammatory bowel disease patients experience chronic abdominal pain. These patients have increased rectal transient receptor potential vanilloid-1 receptor (TRPV1) expression, a key transducer of inflammatory pain. Because inflammatory bowel disease patients in remission exhibit dysbiosis and microbial manipulation alters TRPV1 function, our goal was to examine whether microbial perturbation modulated transient receptor potential function in a mouse model.MethodsMice were given dextran sodium sulfate (DSS) to induce colitis and were allowed to recover. The microbiome was perturbed by using antibiotics as well as fecal microbial transplant (FMT). Visceral and somatic sensitivity were assessed by recording visceromotor responses to colorectal distention and using hot plate/automated Von Frey tests, respectively. Calcium imaging of isolated dorsal root ganglia neurons was used as an in vitro correlate of nociception. The microbiome composition was evaluated via 16S rRNA gene variable region V4 amplicon sequencing, whereas fecal short-chain fatty acids (SCFAs) were assessed by using targeted mass spectrometry.ResultsPostinflammatory DSS mice developed visceral and somatic hyperalgesia. Antibiotic administration during DSS recovery induced visceral, but not somatic, hyperalgesia independent of inflammation. FMT of postinflammatory DSS stool into antibiotic-treated mice increased visceral hypersensitivity, whereas FMT of control stool reversed antibiotics’ sensitizing effects. Postinflammatory mice exhibited both increased SCFA-producing species and fecal acetate/butyrate content compared with controls. Capsaicin-evoked calcium responses were increased in naive dorsal root ganglion neurons incubated with both sodium butyrate/propionate alone and with colonic supernatants derived from postinflammatory mice.ConclusionsThe microbiome plays a central role in postinflammatory visceral hypersensitivity. Microbial-derived SCFAs can sensitize nociceptive neurons and may contribute to the pathogenesis of postinflammatory visceral pain.

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial.

Background:Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment.Methods:This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn’s disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1 year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal.Results:Enrolment began in 2016, and the study is expected to end in 2020.Conclusions:This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission.Clinical trial reference number:EudraCT 2015-001410-10

Mo1944 - A Validated Study Protocol to Compare Microbiome and Mycobiome Profiles of Inflammatory Bowel Disease Patients in Remission and Active Flare

Mo1944 - A Validated Study Protocol to Compare Microbiome and Mycobiome Profiles of Inflammatory Bowel Disease Patients in Remission and Active Flare

P225 Usefulness of monocytosis as biomarker to predict relapse in inflammatory bowel disease patients in remission under maintenance treatment with anti-TNF drugs: A prospective longitudinal cohort study

P225 Usefulness of monocytosis as biomarker to predict relapse in inflammatory bowel disease patients in remission under maintenance treatment with anti-TNF drugs: A prospective longitudinal cohort study

The prevalence of irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease, and the relationship with biochemical markers of disease activity.

A large proportion (25-46%) of adults with inflammatory bowel disease in remission has symptoms of irritable bowel syndrome (IBS), which are thought to reflect ongoing inflammation. Data on paediatric inflammatory bowel disease patients are lacking. To investigate (i) the prevalence of IBS-type symptoms in paediatric inflammatory bowel disease patients in remission and (ii) the relationship of IBS-type symptoms with biochemical markers of disease activity. This cross-sectional study included all patients (<18 years) with Crohn's disease or ulcerative colitis attending the out-patient clinic of one of three Dutch hospitals between March 2014 and June 2015. Clinical disease activity was determined using the abbreviated-PCDAI or PUCAI. Biochemical disease activity was assessed using faecal calprotectin and serum CRP. IBS-symptoms were assessed using physician-administered Rome III-questionnaires. We included 184 patients (92 female; mean age: 14.5 years) (Crohn's disease: 123, ulcerative colitis: 61). The prevalence of IBS-type symptoms in children with inflammatory bowel disease in clinical remission was 6.4% (95% CI: 2.5-11.1%; Crohn's disease: 4.5%; ulcerative colitis: 10.8%). Prevalence of IBS-type symptoms in children with faecal calprotectin <250 μg/g was 16.1% (95% CI: 7.6-25.8%; Crohn's disease: 16.7%; ulcerative colitis: 10.8%). No difference in faecal calprotectin or CRP was found between patients in clinical remission with or without IBS-type symptoms (faecal calprotectin: IBS+ median 58 μg/g, IBS- 221 μg/g, P = 0.12; CRP: IBS+ median 1.4 mg/L, IBS- 1.1 mg/L, P = 0.63). The prevalence of IBS-type symptoms in children with inflammatory bowel disease is highly dependent on the definition of remission. Nonetheless, the prevalence is much lower than that previously reported in studies in adult inflammatory bowel disease patients. IBS-type symptoms appear to be unrelated to gastrointestinal inflammation.

Calprotectin Is a Useful Tool in Distinguishing Coexisting Irritable Bowel-Like Symptoms from That of Occult Inflammation among Inflammatory Bowel Disease Patients in Remission

Background and Aim. In the inflammatory bowel diseases (IBDs), many symptoms are similar to the functional disorder irritable bowel syndrome (IBS). A challenge is thus to distinguish symptoms of IBD from IBS. The aim of this study was to investigate the levels of calprotectin in IBS-positive IBD patients in remission. Methods. Remission was defined as a simple clinical colitis activity index (SCCAI) or simple crohn's disease activity index (SCDAI) score of less than three and less than four, respectively. The Rome II criteria were used to identify cases, and the calprotectin ELISA test was used to quantify calprotectin in stools. Results. The Rome II criteria were fulfilled in 24.6% of ulcerative colitis (UC) patients, while the comparable number for Crohn's disease (CD) was 21.4%. There was a tendency for elevated fecal calprotectin levels in IBS-positive patients, regardless of diagnosis. However, these differences were only significant in CD. Conclusions. Calprotectin levels are elevated in subgroups of IBD patients that are in remission and have coexisting IBS-like symptoms. This study underscores the clinical usefulness of a noninvasive marker to distinguish patients in need of intensified followup from those that do not need further workup.

Fatigue and disease-related worries among inflammatory bowel disease patients in remission; is it a reflection of coexisting IBS-like symptoms? A short report

ObjectivesIrritable bowel syndrome (IBS) like symptoms and fatigue are frequently reported in quiescent inflammatory bowel disease (IBD). We hypothesized that coexisting IBS-like symptoms might be associated with increased levels of fatigue and disease-related worries. MethodsA total of 140 IBD outpatients were assessed. Cut-off for remission was <4 and <3 on the disease activity indices SCDAI and SCCAI. In addition patients on current steroid treatment were excluded. A diagnosis of IBS was based on the Rome criteria. Fatigue was measured with the Fatigue Questionnaire (FQ), disease related worries with the Rating Form of IBD Patient Concerns (RFIPC). ResultsEighty-nine patients fulfilled the criteria for remission. Of these 89 patients, 21 and 30 were IBS positive according to the Rome II and III criteria, respectively. FQ scores were significantly elevated in IBS positive UC patients. Clinical significant differences were also found in relation to RFIPC scores. ConclusionCoexisting IBS-like symptoms among IBD patients in remission are associated with an increased level of fatigue and disease-related worries.

Response Friedman and Sparrow re: Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission. Inflamm Bowel Dis 2011 [Epub ahead of print

Response Friedman and Sparrow re: Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission. Inflamm Bowel Dis 2011 [Epub ahead of print

Response to Clarke K, Regueiro M. Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission. Inflamm Bowel Dis 2011 [Epub ahead of print

Response to Clarke K, Regueiro M. Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission. Inflamm Bowel Dis 2011 [Epub ahead of print

Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission

The emergence of biologic response modifiers and earlier use of immunomodulators for inflammatory bowel disease (IBD) patients have improved outcomes. Durable remissions have been achieved in many IBD patients on these treatments, but the duration of treatment and identifying which patients may stop therapy is yet unresolved. Recently, the term very deep remission (defined as clinical remission [CDAI < 150] and endoscopic remission) has been applied to patients on immunomodulators/biologics who have no clinical symptoms or objective signs of inflammatory disease. Whether or not patients who achieve and maintain a very deep remission may successfully stop treatment is not known. This article will review the current data on stopping treatment in IBD and identify certain factors that are associated with a high relapse rate after discontinuing treatment. Where evidence-based data are lacking, the authors provide their opinion.

T1355 High Prevalence of Obstructive Defecation in Inflammatory Bowel Disease Patients in Remission

T1355 High Prevalence of Obstructive Defecation in Inflammatory Bowel Disease Patients in Remission

Autonomic imbalance during the day in patients with inflammatory bowel disease in remission. Evidence from spectral analysis of heart rate variability over 24 hours

Background. Autonomic function in inflammatory bowel disease has not yet been studied by means of analysis of 24-hour heart rate variability. Aim. To measure heart rate variability in inflammatory bowel disease patients in remission. Patients and methods. Study population comprised 27 patients with inflammatory bowel disease in remission and 28 healthy, sex- and age-matched controls. Two frequency ranges were analysed: low frequency (0.06–0.15 Hz) and high frequency (0.15–0.40 Hz). Results. Mean values of low frequency and low frequency/high frequency ratio were lower in patients than in controls (p<0.001). High frequency in patients tended to be higher than in controls (p=0.09). The only factor that had a marginal effect on heart rate variability indexes was age. In high frequency, there was a significant time effect (p=0.001) for both groups. There was also a significant time effect in low frequency/high frequency ratio in both groups (p<0.001). During daytime, the mean values in low frequency/high frequency ratio were lower in patients than in controls (p<0.001). Conclusions. There is a shift in the autonomic balance in patients with inflammatory bowel disease in remission towards a condition of relative parasympathetic predominance, which, in the first place, reflects a sympathetic pullback. This imbalance has a circadian rhythm and it is more pronounced during the day.

Increased leucocyte adhesiveness/aggregation is a most useful indicator of disease activity in patients with inflammatory bowel disease.

The aim of the study was to determine the comparative usefulness of inflammatory markers, in evaluating disease activity in patients with inflammatory bowel disease. Disease activity was assessed by the Mayo Clinic score for ulcerative colitis, and Harvey-Bradshaw score for Crohn's disease. Five hundred normal blood donors who had no underlying inflammatory condition served as controls. The erythrocyte sedimentation rate, platelet and white blood cell count, C reactive protein, and the leucocyte adhesiveness/aggregation test (LAAT) were determined in each patient. One hundred and twenty four patients with inflammatory bowel disease were tested while in remission and 128 in relapse. Their mean (SD) per cent of aggregated white blood cells in the peripheral blood was 8 (5) and 17 (10) respectively compared with controls 6 (4) (p < 0.0001). Moreover, the LAAT could effectively discriminate between various grades of disease activity, the values in patients with active disease being 13 (6)% in mild, 17 (10)% in moderate, and 26 (10)% in severe disease (p < 0.0001). Other acute phase reactants including the erythrocyte sedimentation rate, the white blood cell count, the platelet count, neutrophil count, as well as, the C reactive protein concentration did not differentiate as well between the various groups. Using logistic regression analysis to differentiate between inflammatory bowel disease patients in remission or relapse, the LAAT was the single best indicator. The addition of any other test did not contribute to the discrimination. Among the different laboratory variables tested only the LAAT significantly discriminated between the five different subgroups of controls, remission and mild, moderate or severe disease activity.

Microalbuminuria in inflammatory bowel disease.

Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.