Natural history and impact of irritable bowel syndrome-type symptoms in inflammatory bowel disease during 6 years of longitudinal follow-up.

BACKGROUND: The long-term natural history and impact of irritable bowel syndrome (IBS)-type symptoms on outcomes in inflammatory bowel disease (IBD) are uncertain. AIM: To assess this in a longitudinal follow-up study of patients in secondary care METHODS: We assessed the natural history of IBS-type symptoms in IBD via Rome III criteria applied at baseline, and 2 and 6 years. We defined longitudinal disease activity as the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. To assess healthcare utilisation, we recorded the number of outpatient clinic attendances and investigations. We also collected anxiety, depression and somatoform symptom scores and quality of life scores during follow-up. RESULTS: Among 125 individuals with Rome III data at all three time points, only 41 (32.8%) never reported IBS-type symptoms. Fifteen patients (12.0%) had IBS-type symptoms at baseline that resolved, 19 (15.2%) had fluctuating symptoms, 35 (28.0%) had new-onset symptoms, and 15 (12.0%) had persistent symptoms. Among more than 300 patients with IBD activity data, IBS-type symptoms were not associated with an increased likelihood of the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. However, the mean numbers of outpatient appointments and endoscopic investigations were significantly higher among those with IBS-type symptoms. Anxiety, depression and somatoform symptom scores were significantly higher, and quality of life scores were significantly lower, in those reporting IBS-type symptoms at least once during the study. CONCLUSIONS: IBS-type symptoms affected more than two-thirds of patients with IBD during >6 years of follow-up and were associated with increased healthcare utilisation, and worse anxiety, depression, somatoform symptom and quality of life scores, but not adverse disease activity outcomes.

Infliximab Therapeutic Drug Monitoring in Inflammatory Bowel Disease Virtual Biologics Clinic Leads to Durable Clinical Results.

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels and anti-drug antibodies in conjunction with symptoms, disease history, and investigations can aid decision-making. This study evaluated 1-year outcomes of patients with decisions that were altered on the basis of TDM results, in order to investigate whether outcomes from TDM-based decisions to adjust or stop IFX treatment are durable. METHODS: We retrospectively collected clinical outcomes 12 months post treatment decisions based on proactive TDM. Patients whose initial treatment decisions were altered on the basis of TDM results were compared with those where the decision remained unchanged. Events of interest were inpatient admissions with active inflammatory bowel disease (IBD), further changes to biologic therapy, and IBD-related health-care costs. RESULTS: Of 189 patients, 54 (28%) had initial treatment decisions altered in the light of TDM results. The 135 patients whose initial decision was not altered in light of TDM results served as the comparator. There were no differences in hospitalization rates or subsequent biologic switches between the altered decision groups and the comparator group. IBD-related health-care costs were higher in those whose initial decision was altered (median GBP 7,912 vs. GBP 6,521; p < 0.0001) due to higher drug costs (median GBP 7,062 vs. GBP 6,012; p < 0.0001). CONCLUSION: Our study demonstrates good outcomes from changes to IFX treatment based on TDM. Patients with a decision to stop, switch, or continue with an adjusted IFX dose experienced comparable clinical outcomes but had higher drug-related expenditure than those whose treatment decision was not altered in light of TDM.

Noninvasive Monitoring of Mantle Cell Lymphoma by Immunoglobulin Gene Next-Generation Sequencing in a Phase 2 Study of Sequential Chemoradioimmunotherapy Followed by Autologous Stem-Cell Rescue.

BACKGROUND: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment. PATIENTS AND METHODS: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay. RESULTS: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse. CONCLUSION: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.

The Association of Introducing a Faecal Calprotectin Testing Pathway for Suspected Inflammatory Bowel Disease in Primary Care and Time to Diagnosis or Treatment.

BACKGROUND: Primary care faecal calprotectin (FC) was introduced in Leeds in 2014 to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome and with the hope that it may reduce time to IBD diagnosis and treatment. This study examines the association of FC with referral routes, time to diagnosis, and time to treatment. METHODS: All patients newly referred to IBD clinics in 2013 and 2016 were studied. Data on referral routes and dates, FC, date of first treatment, and proxy outcomes for disease severity were collected. RESULTS: In 248 patients, there were no differences between 2013 and 2016 cohorts regarding baseline data and disease severity. The number of direct referrals to gastroenterology rose from 3% (2013) to 17% (2016), whilst 10% were diagnosed during emergency admissions. Referrals via suspected cancer pathways remained high (38% in 2013, 28% in 2016), whilst many had initial investigations at independent centres (16% in 2013, 24% in 2016). Time from referral to diagnosis was similar between 2013 (0.77 month) and 2016 (1.10 months, p = 0.2). A total of 48 (33.3%) patients had FC checked prior to referral, and 37.5% of these were referred directly to gastroenterology. Time from diagnosis to treatment reduced from 1.37 months (2013) to 0.72 month (2016, p = 0.01). CONCLUSION: Patients present via a multitude of referral pathways, but FC was associated with increased direct referrals to gastroenterology. We found a variation in time to diagnosis and treatment depending on referral routes. Further work is required to ensure patients with suspected IBD get referred to IBD services in a timely manner.

The influence of the brain-gut axis in inflammatory bowel disease and possible implications for treatment.

Brain-gut interactions affect psychological wellbeing and symptom reporting in functional gastrointestinal disorders; the presence of anxiety or depression is associated with the development of new-onset gastrointestinal symptoms, and the presence of gastrointestinal symptoms is associated with the development of psychological disorders de novo. In inflammatory bowel diseases (IBD), the reporting of irritable bowel syndrome (IBS)-type symptoms by patients with quiescent disease is common, and is associated with psychological disorders, impaired quality of life, and increased health-care use. In IBD, data from observational studies suggest that psychological disorders might be associated with relapse of disease activity, and that inflammatory activity is associated with the development of new psychological disorders, as has been described for functional gastrointestinal disorders such as IBS and functional dyspepsia. The brain-gut axis provides the physiological link between the CNS and gastrointestinal tract that might facilitate these relationships. In IBS, treatments targeting disordered brain-gut axis activity, including psychological therapies and antidepressants, might lead to improved symptoms and quality of life. However, in IBD, the benefit of these treatments is less certain because of a scarcity of interventional studies. Despite the scarcity of trials, observational data suggest that the effect of disordered brain-gut axis activity in IBD is substantial, and scope remains for further well designed trials of psychological therapies and antidepressants, particularly in the subset of patients who have coexistent psychological disorders, or in those who report IBS-type symptoms. Integrating these treatments into a biopsychosocial model of care has the potential to improve both psychological wellbeing and quality of life in some patients with IBD, reducing health-care use and altering the natural history of disease.

Randomized controlled trial: a pilot study of a psychoeducational intervention for fatigue in patients with quiescent inflammatory bowel disease.

INTRODUCTION: Fatigue is a frequent, debilitating symptom of inflammatory bowel disease (IBD). Despite this, studies report dissatisfaction among IBD patients regarding how little attention is given to fatigue-related issues during consultations. We performed a pilot randomized controlled trial (RCT) to assess whether a brief, structured, multidisciplinary psychological support program improved fatigue, mood and quality of life indices in patients with quiescent IBD. METHODS: The intervention consisted of three small-group psychoeducational sessions over 6 months. Primary outcomes were effect on fatigue severity and impact scores. Secondary outcomes included effect on depression, anxiety, somatization scores, generic and disease-specific quality of life. RESULTS: Twenty-three patients were enrolled, 10 in the intervention arm and 13 controls. Mean fatigue severity and impact scores improved for patients in the intervention group (by 14.5-13.1 and 49.7-45.8, respectively), and worsened in controls (by 11.5-12.6 and 33.5-35 respectively). Mean Short Form 36 (SF-36) scores for role limitations due to physical health decreased from 44.4 to 38.9 in the intervention group, but increased from 44.2 to 51.9 among controls. Energy scores in the intervention group improved from 17.8 to 26.6, but only from 31.4 to 31.7 among controls. Short IBD questionnaire scores improved in both groups, from 46.2 to 45.2 in controls compared with 44.4-40 in the intervention group. DISCUSSION: In this small pilot RCT, positive effects were demonstrated on fatigue, energy levels and other quality of life outcomes. Larger, adequately powered studies with longer follow up are required.ClincialTrials.gov identifier: NCT02709434.

Systematic Review and Network Meta-Analysis of Medical Therapies to Prevent Recurrence of Post-Operative Crohn's Disease.

BACKGROUND AND AIMS: Surgery is an important treatment for Crohn's disease [CD], but recurrence occurs in up to 80% of individuals post-operatively. The efficacy of several drugs to prevent post-operative recurrence has been studied in previous meta-analyses, but a number of randomized controlled trials [RCTs] have recently been published. We therefore performed an updated systematic review and network meta-analysis to investigate this issue. METHODS: We performed a comprehensive literature search through to July 2018 to identify RCTs investigating the endoscopic and clinical recurrence of CD at 12 months post-operatively. We performed a random-effects network meta-analysis to produce a pooled relative risk [RR] with 95% confidence intervals [CIs]. We ranked the treatments according to their P-score. RESULTS: We included 10 RCTs, containing 751 patients, in our primary analysis of endoscopic recurrence of CD at 12 months. Anti-tumour necrosis factor [TNF]-α therapies were significantly better than placebo, either alone [P-score 0.98, RR 0.13; 95% CI 0.04-0.39] or in combination with 5-aminosalicylates [5-ASAs] [P-score 0.81, RR 0.30; 95% CI 0.12-0.75], or 5-nitroimidazoles [P-score 0.75, RR 0.40; 95% CI 0.23-0.69]. Combination therapy with a thiopurine and 5-nitroimidazole was also more effective than placebo [P-score 0.59, RR 0.56; 95% CI 0.40-0.80], as was thiopurine monotherapy [P-score 0.31, RR 0.84; 95% CI 0.74-0.94]. However, neither 5-nitroimidazoles nor 5-ASAs alone were superior to placebo. CONCLUSIONS: In network meta-analysis, anti-TNF-α therapies alone, or in combination, appear to be the best medications for preventing endoscopic post-operative recurrence of CD.

The Effect of Antidepressants on the Course of Inflammatory Bowel Disease.

Background and Aims: Mood may have an important role in the natural history of inflammatory bowel disease (IBD). However, the impact of antidepressant use on prognosis is unknown. We aimed to address this in a longitudinal study in a referral population. Methods: We collected demographic data, clinical disease activity and mood using validated questionnaires, and antidepressant use at baseline. Longitudinal disease activity was defined by disease flare or need for glucocorticosteroids, escalation of medical therapy, hospitalisation, or intestinal resection. We compared rates of these over a minimum period of 2 years according to antidepressant use at baseline. Results: In total, 331 patients provided complete data, of whom 54 (15.8%) were taking an antidepressant at study entry. Older age, female gender, and abnormal mood scores were associated with antidepressant use. During longitudinal follow-up, there was a trend towards lower rates of any of the four endpoints of IBD activity of interest in patients with abnormal anxiety scores at baseline and who were receiving an antidepressant (42.3% versus 64.6%, P = 0.05). Based on univariate Cox regression analysis, there was a trend towards lower rates of escalation of medical therapy among patients receiving antidepressants at baseline (hazard ratio (HR) = 0.59; 95% confidence interval (CI) 0.35-1.00, P = 0.05). None of the differences observed persisted after multivariate Cox regression. Conclusions: Antidepressants may have some beneficial effects on the natural history of IBD, but larger studies with longer follow-up are required. Whether these effects are limited to patients with abnormal mood remains uncertain.

Golimumab induction and maintenance for moderate to severe ulcerative colitis: results from GO-COLITIS (Golimumab: a Phase 4, UK, open label, single arm study on its utilization and impact in ulcerative Colitis).

OBJECTIVE: GO-COLITIS aimed to measure the effectiveness of subcutaneous golimumab in tumour necrosis factor-α antagonist-naive patients with moderate to severe ulcerative colitis (UC) despite conventional treatment. DESIGN: GO-COLITIS was an open label, single arm, phase 4 study with a pragmatic design which reflected UK clinical practice. Adult patients were eligible if diagnosed with UC ≥3 months, partial Mayo score (PMS) 4-9. Patients received subcutaneous golimumab induction (200 mg initially and 100 mg at week 2) followed at week 6 by 50 mg or 100 mg (depending on weight) every 4 weeks until week 54 with a 12-week follow-up. Efficacy was measured by PMS at baseline, week 6, 30, 54 and 66. Health-related quality of life (HRQoL; Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQol Group 5 Dimensions Health Questionnaire (EQ-5D)) was assessed at baseline, week 6 and week 54. All safety adverse events (AEs) were recorded. RESULTS: 207 patients were enrolled and 205 received golimumab (full analysis set (FAS)205). At week 6, 68.8% (95% CI 62.0% to 75.1%) and 38.5% (95% CI 31.8% to 45.6%) of patients were in response and remission, respectively, using PMS. At the end of the induction phase, 140/141 patients in clinical response continued into the maintenance phase (Maintenance FAS). Sustained clinical response through week 54 was achieved in 51/205 (24.9%) of the FAS205 population and 51/140 (36.4%) of the Maintenance FAS population. Statistically significant improvements from baseline to week 6 were observed for the IBDQ total score and for each IBDQ domain score (bowel symptoms, emotional function, systemic symptoms and social function), as well as the EQ-5D index score and associated visual analogue scale score (p<0.0001). Improvement of HRQoL was sustained through week 54. Serious AEs leading to treatment discontinuation occurred in 8.8% of patients. CONCLUSION: In this study measuring patient-reported outcomes in patients with moderate to severe UC, golimumab induced and maintained response as measured by PMS and significantly improved quality of life measures. TRIAL REGISTRATION NUMBER: NCT02092285; 2013-004583-56.

Efficacy and tolerability of initiating, or switching to, infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD): a large single-centre experience.

OBJECTIVES: Recently, the infliximab biosimilar (CT-P13) received market authorisation for inflammatory bowel disease (IBD), allowing cost benefits when switching to CT-P13. We aim to assess the efficacy and safety of switching from originator infliximab to CT-P13 for new and existing patients. MATERIAL AND METHODS: Treatment response, remission, primary and secondary loss of response rates, and adverse events in patients who initiated infliximab originator in the 12 months pre-switch (n = 53) were compared with the patients who initiated CT-P13 in the 12 months post-switch (n = 69). Sustained responses were compared for existing infliximab originator patients who switched to CT-P13 (n = 191) and those who continued with the originator (n = 19). RESULTS: There was no difference in remission (58.1% vs. 47.4%, p = .37), response (12.6% vs. 10.5%, p = .80), secondary loss of response (24.6% vs. 42.1%, p = .10), or adverse events (4.7% vs. 0% p = 1.0) between those who switched to CT-P13 and those who continued infliximab originator. There was no difference in remission (42.0% vs. 26.4%, p = .074), response (21.7% vs. 22.6%, p = .91), primary non-response (5.8% vs. 15.1%, p = .09), secondary loss of response (21.7% vs. 22.6%, p = .91), or adverse events (8.7% vs. 11.3%, p = .63) in those who initiated CT-P13 compared with infliximab originator. CONCLUSIONS: There was no difference in the efficacy and safety of infliximab originator and CT-P13 during the first 12 months after switching.

No Significant Association Between the Fecal Microbiome and the Presence of Irritable Bowel Syndrome-type Symptoms in Patients with Quiescent Inflammatory Bowel Disease.

Background: The microbiome is implicated in the pathogenesis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Whether a distinct microbiome profile is associated with the reporting of IBS-type symptoms in IBD patients is uncertain. We aimed to resolve this issue using a cross-sectional study design. Methods: Using clinical disease activity indices, the Rome III criteria for IBS and fecal calprotectin levels, we divided IBD patients into 4 groups: IBS-type symptoms, quiescent disease, occult inflammation, and active disease. A16S rRNA microbiome analysis was performed to determine whether any taxa were differentially abundant, and whether there were any differences in alpha or beta diversity in patients reporting IBS-type symptoms compared with those in the other 3 groups. Results: Of 270 patients included, 70 (25.9%) had IBS-type symptoms, 81 (30.0%) quiescent IBD, 66 (24.4%) occult inflammation, and 53 (19.6%) active IBD. At phylum level, there was a nonsignificant increase in the abundance of Actinobacteria in patients reporting IBS-type symptoms, but no other differences at any taxonomic level. When compared with patients reporting IBS-type symptoms, mean alpha diversity was greater in patients with quiescent disease, although this was nonsignificant (28.6 vs 31.7, P = 0.33), and similar to those with occult inflammation and active disease. Beta diversity variation among the 4 groups was significant for unweighted (P = 0.002) but not weighted (P = 0.21) UniFrac analysis. Conclusions: Reporting IBS-type symptoms was not associated with distinct microbiome alterations. Unmeasured confounding could have impacted the significance of our findings.

Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin.

OBJECTIVES: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. METHODS: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn's disease (CD). Disease activity was assessed using clinical indices, self-reported flare or faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. RESULTS: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84-17.0] and UC (OR 10.8; 95% CI 1.8-64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49-5.39; and OR 0.21; 95% CI 0.21-1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84-34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46-6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47-43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28-14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. CONCLUSIONS: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

Bi-directionality of Brain-Gut Interactions in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are associated with mood disorders, such as anxiety or depression, but it is not clear whether one contributes to development of the other, or if the interaction is bi-directional (anxiety or depression contributes to the progression of IBD, and IBD affects psychological health). We performed a 2-year longitudinal prospective study of patients in secondary to care investigate the bi-directionality of IBD and mood disorders. METHODS: We collected data from 405 adult patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) from November 2012 through June 2017. Demographic features, subtypes of IBD, treatments, symptoms, somatization, and fecal level of calprotectin were recorded at baseline. IBD activity was determined at baseline and after the follow-up period (2 years or more) using the Harvey-Bradshaw Index for CD and the Simple Clinical Colitis Activity Index for UC (scores ≥5 used to define disease activity). Anxiety and depression data were collected using the Hospital Anxiety and Depression Scale (HADS), at baseline and after the follow-up period. Objective markers of disease activity, including glucocorticosteroid prescription or flare of disease activity, escalation of therapy, hospitalization secondary to IBD activity, and intestinal resection during follow-up were assessed via case note review. A brain-gut direction of disease activity was defined as development of new IBD activity in patients with quiescent IBD and abnormal HADS scores at baseline. A gut-brain direction of disease activity was defined by subsequent development of abnormal HADS scores in patients with active IBD and normal HADS scores at baseline. We performed multivariate Cox regression controlling for patient characteristics and follow-up duration. RESULTS: Baseline CD or UC disease activity were associated with an almost 6-fold increase in risk for a later abnormal anxiety score (hazard ratio [HR], 5.77; 95% CI, 1.89-17.7). In patients with quiescent IBD at baseline, baseline abnormal anxiety scores were associated with later need for glucocorticosteroid prescription or flare of IBD activity (HR, 2.08; 95% CI, 1.31-3.30) and escalation of therapy (HR, 1.82; 95% CI, 1.19-2.80). These associations persisted when normal IBD activity index scores and fecal level of calprotectin <250 µg/g were used to define quiescent disease at baseline. CONCLUSIONS: In a 2-year study of patients with CD or UC, we found evidence for bi-directional effects of IBD activity and psychological disorders. Patients with IBD should be monitored for psychological well-being.

Infliximab Therapeutic Drug Monitoring Changes Clinical Decisions in a Virtual Biologics Clinic for Inflammatory Bowel Disease.

BACKGROUND: Virtual biologics clinics are often used to review patients with inflammatory bowel disease receiving biological therapy, with decisions whether to continue, switch, or stop therapy made based on review of symptoms, disease history, and investigations. We aimed to investigate whether therapeutic drug monitoring of infliximab (IFX) trough levels and anti-drug antibodies influences decision making within a virtual biologics clinic. METHODS: For all patients with inflammatory bowel disease receiving IFX maintenance therapy, 2 decisions were recorded in a preset format. The first decision was based on assessment of clinical details, with clinicians blinded to IFX trough levels and anti-drug antibodies. The second decision was made after unblinding of these data. RESULTS: Among 191 patients (mean age 40 years; 106 (55.5%) male), IFX trough levels were sub-therapeutic in 53 (27.7%) (<2 mg/L), therapeutic in 100 (52.4%), and supra-therapeutic in 38 (19.9%) (>6 mg/L). Anti-drug antibodies were detected in 58 (30.4%), and were >50 AU/mL in 26 (13.6%). Blinded treatment decisions were changed on unblinding these data in 56 cases (29.3%; P < 0.0001). Knowledge of these data led to 7 (3.7%) patients receiving intensified IFX, whereas 33 (17.3%) patients were able to either dose de-escalate or stop IFX. CONCLUSIONS: Basing decisions on therapeutic drug monitoring, rather than clinical acumen alone, led to a change in almost one-third of decisions made, offering considerable cost savings and reducing exposure to potentially toxic therapies. Routine therapeutic drug monitoring should be considered an integral part of annual biologics assessment (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B629).

Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. AIM: To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). RESULTS: The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. CONCLUSIONS: VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.