Low Subjective Wellbeing Is Associated with Psychological Distress in People Living with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a common and debilitating disease of the gastrointestinal tract. Psychological distress is highly comorbid to IBD, especially during periods of active disease. However, a controversy exists on how to best manage its symptoms in the IBD population. AIMS: This study aimed to explore protective and risk factors of psychological distress in IBD. METHODS: A cross-sectional online survey was conducted via social media and online patient forums. Respondents (N = 235) filled out questionnaires on demographics, health characteristics and a range of psychological variables. Measures of pain, disease activity, comorbid functional symptom severity, social support, subjective wellbeing, sleep quality, fatigue, stress, age, BMI and gender were entered into the Classification and Regression Tree Analysis model. RESULTS: Overall, 87 participants (37%) reported distress. Self-reported stress significantly discriminated between cases of probable psychological distress. In those with high stress, patients with and without probable psychological distress were separated by subjective wellbeing. Among patients with low stress, fatigue was the primary discriminator. CONCLUSIONS: Monitoring patients for low subjective wellbeing and high stress in clinical settings could offer an opportunity to engage in early intervention to limit psychological distress development. Monitoring for fatigue in patients who seem otherwise psychologically well could offer preventative benefits.

Patients with inflammatory bowel disease at risk of sub-optimal outcomes report poorer biopsychosocial functioning than controls: data from two cross-sectional surveys.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Standard treatment focuses on reducing the inflammatory burden, however, not all patients respond adequately to conventional medical therapy. These patients, referred to as Patients at Risk of Suboptimal Outcomes (PARSO), have not been studied collectively. The present study aimed to understand the biopsychosocial characteristics of patients with IBD at risk of sub-optimal outcomes for targeted multi-disciplinary treatment to encourage optimal outcomes. Two cross-sectional online surveys, including 760 PARSO and 208 control (non-PARSO) participants, were conducted and their data combined. Biopsychosocial factors included quality of life, pain, disease activity, wellbeing, fatigue, stress, social support, and sleep difficulties. Results suggest that active disease, quality of life, stress, social support, sleep difficulties, fatigue, wellbeing, smoking status, IBD subtype, and pain are significantly associated with membership in a subgroup of PARSO. We also used logistic regression to explore variables associated with the total likelihood of PARSO status. Overall, the model predicted the at-risk status to a substantial degree (R2-2ll = .41, x2 = 401.53, p < .001). Younger age in years, female sex, Crohn's disease, and greater measured and subjective disease activity significantly increased the likelihood of participants being identified as PARSO; OR CI95% = 0.96 (0.95, 0.97); OR CI95% = 4.46 (2.95, 6.71); OR CI95% = 1.58 (1.05, 2.37); OR CI95% = 3.52 (2.18, 5.69); OR CI95% = 45.99 (14.11, 149.89). A biopsychosocial and personalised approach to IBD care might be necessary to support those at risk of suboptimal outcomes in achieving better long-term wellbeing.

Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study.

BACKGROUND AND AIMS: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.

Perspectives on an Acceptance and Commitment Therapy (ACT) based program for patients with inflammatory bowel disease and comorbid anxiety and/or depressive symptoms.

Background and aim: Individuals with inflammatory bowel disease (IBD) suffer higher rates of anxiety and depression than the general population, however, few psychological interventions are designed for this population. Acceptance and Commitment Therapy (ACT), aimed to increase psychological flexibility, may be useful to address the unique concerns of IBD sufferers. This study aimed to explore stakeholder perspectives on an ACT-based intervention prototype tailored to people with IBD and comorbid anxiety and/or depressive symptoms.Methods: An Intervention Mapping methodology guided intervention design. A qualitative exploratory design was used to investigate the perspectives of stakeholders. Focus groups or interviews obtained feedback from IBD patients of a major regional hospital, and health providers to IBD patients Australia-wide.Results: Findings were analysed using template analysis. Data saturation was reached at 19 participants (11 patients and 8 health professionals). Participants' perspectives on the ACT-based intervention were distributed across four themes: (1) Barriers to access and participation; (2) Timing in the illness trajectory; (3) ACT is useful for IBD; and (4) The more support, the better.Conclusion: The findings suggest that an ACT modality and blended delivery design is well received by patients and health professionals, providing recommendations to future researchers and clinicians on intervention design.

Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

OBJECTIVE: We evaluated the influence of the renin-angiotensin system (RAS) on intestinal inflammation and fibrosis. DESIGN: Cultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1-7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies. RESULTS: Human colonic myofibroblast proliferation was reduced by Ang (1-7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1-7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson's trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=-0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation. CONCLUSIONS: The RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

Faecal calprotectin delivers on convenience, cost reduction and clinical decision-making in inflammatory bowel disease: a real-world cohort study.

BACKGROUND: Faecal calprotectin (FC) is an accurate biomarker of disease activity in inflammatory bowel disease (IBD), yet the cost/resource implications of incorporating FC into 'real-world' practice remain uncertain. AIM: To evaluate the utility of FC in clinical decision-making and on healthcare costs in IBD. METHODS: Retrospective data, including colonoscopy/other investigations, medication, admission and surgical data, were collected from hospital records and compared between two groups: pre-FC historical cohort (2005-2009) where colonoscopy was used to assess IBD activity versus the cohort where FC was used first instead (2010-2014). Post-test costs were also compared. RESULTS: A total of 357 FC tests (246 patients, 2010-2014) and 450 colonoscopies (268 patients, 2005-2009) were performed. On subsequent review, both FC and colonoscopy (in their respective cohorts) were associated with changes in management in 50.7 versus 56.2% (P = 0.14), respectively, with similar proportions of subsequent IBD-related investigations within 6 months (21.8 vs 21.9%, P = 1.0). Prior to FC availability (2005-2009), a colonoscopy for disease reassessment cost AU$606 578 (cost per patient-year $1887.34) versus AU$282 048 (cost per patient-year $968.60) when FC ± colonoscopy was used (2010-2014). Within the FC cohort, 73.6% did not proceed to colonoscopy within 6 months post-FC, and 60.6% had not undergone colonoscopy post-FC by the end of follow up (median 1.8 years (0.1, 4.6) post-FC). Those with FC ≥ 250 were scoped earlier than those with FC < 100 µg/mL (median 0.49 vs 1.0 years, P = 0.03). CONCLUSION: Introduction of FC into routine IBD care aided changes in clinical management in a similar proportion, yet at potentially half the total cost, compared to a historical colonoscopy-only cohort at the same centre.

Never underestimate inflammatory bowel disease: High prevalence rates and confirmation of high incidence rates in Australia.

BACKGROUND AND AIMS: Regional variations in inflammatory bowel disease (IBD) rates have been observed. Limited epidemiological data are available from Australasia. IBD prevalence rates have never been assessed in an Australian population-based setting. In addition, there are few historical IBD incidence data to allow assessment of rate changes. The aims were to calculate Australia's first population-based IBD prevalence rates, to reassess local IBD incidence rates, and to establish a population-based inception cohort. METHODS: An observational, prospective population-based epidemiological study was performed to assess IBD prevalence and incidence rates from July 2010 to June 2011 in a geographically defined Australian population (Barwon, Victoria). RESULTS: There were 1011 prevalent IBD cases identified, representing a crude point prevalence rate of 344.6 per 100,000 on June 30, 2011. Crohn's disease was the most common prevalent subtype. Seventy-one incident cases of IBD were identified, with a crude incidence rate of 24.2 per 100,000. Crohn's disease was again more common. Local incidence rates have not changed between 2007 and the present study. All incident cases were successfully incorporated into an inception cohort. CONCLUSION: The burden of IBD in our local region is high. Demographic similarities allow these results to be applied to the broader Australian community. We propose that the number of existing and new cases each year in Australia has been previously underestimated. These revised figures will be important when planning the provision of health resources for these patients in the future and when assessing need for research funding priorities.

Clinical trial: A Mediterranean diet is feasible and improves gastrointestinal and psychological symptoms in irritable bowel syndrome.

BACKGROUND: Diet is fundamental to the care of irritable bowel syndrome (IBS). However, some approaches are not appropriate for individuals experiencing psychological symptoms. AIMS: To assess feasibility of a Mediterranean diet in IBS and its impact on gastrointestinal and psychological symptoms. METHODS: We recruited adults with Rome IV IBS and mild or moderate anxiety and/or depressive symptoms to an unblinded 6-week randomised controlled trial. Patients were randomised to Mediterranean diet counselling or habitual diet. We collected gastrointestinal and psychological symptom data, dietary data and stool samples for metagenomic sequencing. RESULTS: We randomised 59 individuals (29 Mediterranean diet, 30 control); 48 completed the study. The Mediterranean Diet Adherence Screener score was higher in the Mediterranean diet group than controls at week 6 (7.5 [95% CI: 6.9-8.0] vs. 5.7 [5.2-6.3], p < 0.001), and there was a greater score increase than controls (2.1 [95% CI: 1.3-2.9] vs. 0.5 [95% CI: 0.1-1.0], p = 0.004), demonstrating Mediterranean diet feasibility. There was a greater proportion of gastrointestinal symptom responders in the Mediterranean diet group than controls (24/29, 83% vs. 11/30, 37%, p < 0.001) and depression responders (15/29, 52% vs. 6/30 20%, p = 0.015). There was no difference in FODMAP intake at week 6 (p = 0.51). Gastrointestinal adverse events were similar (p = 0.588). There were no differences in change in microbiome parameters between groups. CONCLUSIONS: A Mediterranean diet is feasible in IBS and leads to improvement in gastrointestinal and psychological symptoms. Although this study was unblinded, these findings together with the broader benefits of the Mediterranean diet, provide strong impetus for future research in IBS. Australia New Zealand Clinical Trials Registry: ACTRN12620001362987.

Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial.

BACKGROUND: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC. METHODS: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed. FINDINGS: Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study. INTERPRETATION: Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3. FUNDING: Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag.

Mindfulness Practice Is Associated With Subjective Wellbeing Homeostasis Resilience in People With Crohn's Disease but Not Ulcerative Colitis.

Objectives: People with Crohn's disease and ulcerative colitis (inflammatory bowel disease: IBD), commonly experience high levels of depressive symptoms and stress and low levels of subjective wellbeing (SWB). Mindfulness is increasingly considered an adjuvant IBD treatment. The relationships between depression, disease symptoms and mindfulness have not previously been considered within the theory of SWB homeostasis. This theory states that SWB is normally maintained by a homeostatic system around a setpoint range but can fail when psychological challenges dominate consciousness. This study explored the relationship among SWB and patient-reported psychological and IBD symptoms and investigated whether mindfulness practice is independently associated with SWB homeostatic resilience. Design: This cross-sectional study recruited participants through online IBD support groups. Methods: Participants (n = 739; 62% Crohn's disease) detailed symptoms of depression and stress, patient-reported disease symptoms, and regularity of mindfulness practice. Results: The sample had significantly lower SWB (hedges g = -0.98) than normative data. A logistic regression found mindfulness practice doubled the Crohn's disease participants' odds of reporting SWB within the normal homeostatic range, after controlling for psychological, physical, and demographic variables (OR 2.15, 95% CI: 1.27, 3.66). A one-point increase of patient-reported bowel symptoms reduced the participant's odds of reporting SWB in the normal homeostatic range by about a third (OR 0.66, 95% CI: 0.50, 0.85). However, the influence of mindfulness or disease symptoms on SWB was not observed for people with ulcerative colitis. Conclusion: These findings provide initial evidence for an association between mindfulness and SWB homeostatic resilience in a clinical population.

Can an online expressive writing program support people with inflammatory bowel disease? A feasibility randomised controlled trial.

BACKGROUND: We explored feasibility, acceptability and preliminary efficacy of an online writing intervention (WriteforIBD) against an active control condition for distress in people with inflammatory bowel disease (IBD) at the time of the COVID-19 pandemic. METHODS: A feasibility RCT was conducted in 19 adults (89.5% female, aged 20-69 years) with IBD and mild-moderate distress. Participants allocated to the WriteForIBD group completed a 4-day 30-min writing program adapted for IBD. The active control group wrote about trivial topics provided by researchers. Feasibility was established based on the recruitment and retention while acceptability based on completion rates and a numeric rating scale. All participants completed measures of mental health and disease activity before and after the intervention (one week) and at follow-up three months after the study commencement. RESULTS: The retention rate in the study was high (100% WriteForIBD; 82% control). All participants attended every session. 84.2% of participants were satisfied with the intervention. All participants reported a significant improvement in IBD-Control immediately after the intervention; F (2, 33.7) = 7.641, p = .002. A significant interaction of group*time for resilience was noted, R2 = 0.19, p < .001, with the active control group reporting a significant decline in resilience from the first follow-up to three months while no significant change in resilience for the WriteForIBD group was recorded. CONCLUSIONS: Online expressive writing is potentially feasible and highly acceptable to people with IBD who report distress. Future large-scale trials should explore the intervention that is adapted from this feasibility study. REGISTRATION: ID: ACTRN12620000448943p.

Lived experience in people with inflammatory bowel disease and comorbid anxiety and depression in the United Kingdom and Australia.

This study explored the lived experience of people with inflammatory bowel disease and anxiety/depression. It utilised a deductive biopsychosocial framework. Overall, 24 patients and 20 healthcare professionals from two countries participated. In the United Kingdom, the main themes included (1) bidirectional relationship between inflammatory bowel disease and mental health, (2) the need for healthcare integration and (3) lack of awareness about the disease. In Australia, (1) the 'vicious cycle' of inflammatory bowel disease and psychosocial health, (2) the need for biopsychosocial healthcare integration and (3) the stigma of a hidden disease. Better communication around mental illness is essential in improving inflammatory bowel disease healthcare.

Expressive writing to combat distress associated with the COVID-19 pandemic in people with inflammatory bowel disease (WriteForIBD): A trial protocol.

OBJECTIVE: A large proportion of patients with inflammatory bowel disease (IBD) receive immunosuppressive medication, may be at higher risk of complications if they contract SARS-CoV-2 virus, and therefore report high levels of COVID-19-related distress. This trial will evaluate a brief, evidence-based, online, group-based expressive writing intervention to reduce COVID-19-related distress in people living with IBD at the time of pandemic. METHODS: A parallel double-blind randomised controlled trial will be conducted. Overall, up to 154 adult participants with IBD and mild-moderate distress will be recruited via patient organisations. Participants will be allocated to the expressive writing intervention or an active control group. All participants will complete questionnaires including measures of distress, quality of life, resilience, self-efficacy, social support and disease activity before and after the intervention (1 week) and at 3 months post-intervention. The expressive writing group will participate in the evidenced-based 4-day writing program adapted from Pennebaker and Beall, 1986. The active control group will write about untherapeutic topics provided by researchers. Statistical analysis will be carried out on an intention-to-treat basis and will involve linear mixed effects models. CONCLUSIONS: If successful, this simple intervention may bring personal and societal benefits, particularly because it is low cost, can be easily implemented online, ensuring social distancing, and be made widely available, during future disasters and to help with trauma-related distress in IBD. TRIAL REGISTRATION: The trial has been prospectively registered in the Australian New Zealand Trial Registry - ACTRN12620000448943p.

Exploration of Predictive Biomarkers of Early Infliximab Response in Acute Severe Colitis: A Prospective Pilot Study.

BACKGROUND: The outcomes of acute severe ulcerative colitis [ASUC] appear to be dependent on early intervention with the first and/or further infliximab [IFX] doses, although parameters to guide decision-making remain uncertain. AIM: To assess whether serum/faecal IFX levels and inflammatory biomarkers early after IFX dose can predict ASUC outcomes. METHODS: This prospective pilot study consecutively recruited inpatients with steroid-refractory ASUC, who then received 1-3 IFX rescue doses [5 mg/kg per dose] at the discretion of the treating clinician. Serum IFX, C-reactive protein [CRP], albumin and faecal calprotectin [FC] concentrations were measured daily as an inpatient, and then 7, 14, 28 and 42 days post-first IFX. Faecal IFX was measured 1 day post-IFX. The primary end point was clinical remission (partial Mayo [PM] = 0) and CRP ≤3 mg/l at 6 weeks. Secondary end points were 12-week clinical remission or colectomy during follow-up. RESULTS: Of 24 ASUC patients with a median follow-up of 28 months [range 13-44], 10 [42%] achieved remission at 6 weeks, 12 [50%] achieved 12-week remission, six [25%] had colectomy. In total, 97% received either two or three IFX doses. Post-first dose, receiver-operator curve-derived cutoffs of the area-under-curve [AUC, Days 4-7] concentrations for serum IFX, FC and PM scores each predicted the primary end point with 100% sensitivity, and predicted future colectomy with 89-94% sensitivity. In multivariate analyses, faecal IFX >1 µg/g (odds ratio [OR] 0.04 [0.2, 0.9]), PM AUCd1-3 < 20 (OR 20.2 [1.01, 404], each P < 0.05), FC AUCd1-3 < 10000 µg/ml [OR 13.6 [0.6, 294], trend only, p = 0.09) were each associated with clinical and CRP remission [6 weeks]. CONCLUSIONS: In ASUC, post-first dose IFX, early assessment of serum/faecal IFX, calprotectin and PM scores can accurately predict future remission and colectomy, and thus potentially aid in decision-making, i.e. accelerated IFX dosing or surgical planning if/when needed.

Low-dose thiopurine with allopurinol co-therapy overcomes thiopurine intolerance and allows thiopurine continuation in inflammatory bowel disease.

AIMS: To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. METHODS: A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. RESULTS: Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohn's disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, p = <0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review. CONCLUSION: Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases.

Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis.

INTRODUCTION: Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS: A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented. RESULTS: This review discusses the concept of CMV reactivation which frequently occurs in inflammatory bowel disease-related colitis, most commonly in those presenting with steroid-refractory colitis. In this context, although signifying a poorer prognosis, in most cases, the virus is nonpathogenic and thus antiviral treatment is unhelpful. However, when reactivation gives rise to true CMV disease (colitis) as best discriminated by histology with immunohistochemistry (and the density of such) in colonic biopsy tissue, the patient does benefit from antivirals. CONCLUSION: Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.

The role of thiopurine metabolite monitoring in inflammatory bowel disease.

Thiopurines are the mainstay of medical management in inflammatory bowel disease (IBD), especially in the maintenance of disease remission. Given the limited IBD armamentarium it is important to optimize each therapy before switching to an alternative drug. Conventional weight based dosing of thiopurines in IBD leads to intolerance or inefficacy in many patients. More recently increased knowledge of their metabolism has allowed for dose optimization using thiopurine metabolite levels, namely 6-thioguanine nucleotides and 6-methylmercaptopurine, with the potential for improved outcomes in patients with IBD. This review will outline the current understanding of thiopurine metabolism and pharmacogenomics and will describe the clinical application of this knowledge in the optimization of thiopurines in individual patients.