Adolescents and young adults communicating with gastroenterologists: variation in inflammatory bowel disease clinical communication.

OBJECTIVES: This study explored the variation in emerging adults' communication with gastroenterologists around the management of inflammatory bowel disease (IBD). METHODS: Nineteen emerging adults with IBD aged 18-25 and seven gastroenterologists participated in the study. Outpatient specialist consultations of consenting participants were audio-recorded and transcribed. Transcribed consultations were analysed in terms of the linguistic structure of the consultations and the gastroenterologist-patient role relationship. RESULTS: Variations in the emerging adults' communication with their gastroenterologists stem partly from variation in their ability, opportunity, or need to contribute to the different phases of the consultation and partly from variations in the gastroenterologists' style of communication. Gastroenterologists differed in the construction of their role relationship with the patient, resulting in variations in employing empowering strategies including eliciting, exploring, and clarifying the patient's concerns, sharing clinical reasoning, and validating the patient experience. Variations were also observed in the length of appointments and the gastroenterologists' assessment and addressing of adherence issues. Techniques used by the gastroenterologist varied (1) from simply confirming adherence, to a comprehensive assessment of the patient's understanding of their management plan and their feedback, and (2) from use of persuasion to values calibration. CONCLUSIONS: Evidence-based consumer interventions and communication guidelines for clinicians are needed to address the identified variations in providing care to emerging adults living with chronic conditions.

Colonic Epstein-Barr Virus-Associated Mucocutaneous Ulcer Associated With Ulcerative Colitis.

Epstein-Barr virus-associated mucocutaneous ulcer is a rare lymphoproliferative disorder that occurs in immunosuppressed states that can develop in the gastrointestinal tract and mimic inflammatory bowel disease or other malignancies. We present the case of a 61-year-old man who presented with concurrent acute severe ulcerative colitis and colonic Epstein-Barr virus-associated mucocutaneous ulcer requiring rituximab therapy and a subtotal colectomy.

Proactive Metabolite Testing in Patients on Thiopurine May Yield Long-Term Clinical Benefits in Inflammatory Bowel Disease.

BACKGROUND: The thiopurine medications are well established in the treatment of inflammatory bowel disease (IBD). There is significant variation in levels of toxic and therapeutic metabolites. Current data from small or short-term studies support therapeutic drug monitoring (TDM) in assessing azathioprine (AZA) and 6-mercaptopurine (6MP). TDM of thiopurines involves measurement and interpretation of metabolites 6-TGN and 6-MMPR. AIMS: This study aimed to assess long-cterm outcomes of patients on thiopurines following therapeutic drug monitoring. METHODS: A multicenter retrospective observational study of outcomes post thiopurine TDM was conducted. Demographics, disease characteristics, physician global assessment, IBD therapy at baseline TDM and again at 12 months were collected. Clinical outcomes were analyzed according to TDM result, and indication for TDM including proactive and other indications. RESULTS: The study included 541 patients. Only 39% of patients had appropriate dosing of thiopurines. AZA/6MP TDM informed a management change in 61.9%, and enabled 88.8% of the cohort to continue AZA/6MP following TDM. At 12 months following TDM the majority (74.1%) of the cohort remained on AZA/6MP. Clinical remission was higher at 12-months following thiopurines TDM (68%) compared to baseline (37%), including proactive TDM. Post TDM, 13.0% of patients were identified as shunters and commenced on thiopurine-allopurinol co-therapy. CONCLUSION: Thiopurine TDM resulted in a change in management for the majority of patients. Post TDM significantly more patients were in remission. TDM allowed the identification of non-adherence and shunters who, without intervention, would not reach therapeutic drug levels. Proactive TDM allowed identification and management of inappropriate dosing, and was associated with increased levels of clinical remission.

To scope or not - the challenges of managing patients with positive fecal occult blood test after recent colonoscopy.

BACKGROUND: Colorectal cancer (CRC) is a major health problem. There is minimal consensus of the appropriate approach to manage patients with positive immunochemical fecal occult blood test (iFOBT), following a recent colonoscopy. AIM: To determine the prevalence of advanced neoplasia in patients with a positive iFOBT after a recent colonoscopy, and clinical and endoscopic predictors for advanced neoplasia. METHODS: The study recruited iFOBT positive patients who underwent colonoscopy between July 2015 to March 2020. Data collected included demographics, clinical characteristics, previous and current colonoscopy findings. Primary outcome was the prevalence of CRC and advanced neoplasia in a patient with positive iFOBT and previous colonoscopy. Secondary outcomes included identifying any clinical and endoscopic predictors for advanced neoplasia. RESULTS: The study included 1051 patients (male 53.6%; median age 63). Forty-two (4.0%) patients were diagnosed with CRC, 513 (48.8%) with adenoma/sessile serrated lesion (A-SSL) and 257 (24.5%) with advanced A-SSL (AA-SSL). A previous colonoscopy had been performed in 319 (30.3%). In this cohort, four (1.3%) were diagnosed with CRC, 146 (45.8%) with A-SSL and 56 (17.6%) with AA-SSL. Among those who had a colonoscopy within 4 years, none had CRC and 7 had AA-SSL. Of the 732 patients with no prior colonoscopy, there were 38 CRCs (5.2%). Independent predictors for advanced neoplasia were male [odds ratio (OR) = 1.80; 95% confidence interval (CI): 1.35-2.40; P < 0.001), age (OR = 1.04; 95%CI: 1.02-1.06; P < 0.001) and no previous colonoscopy (OR = 2.07; 95%CI: 1.49-2.87; P < 0.001). CONCLUSION: A previous colonoscopy, irrespective of its result, was associated with low prevalence of advanced neoplasia, and if performed within four years of a positive iFOBT result, was protective against CRC.

Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn's disease.

BACKGROUND: Tumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn's disease (CD), but not all patients achieve fistula healing. AIM: To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels. METHODS: In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test, t test or Mann-Whitney U test. RESULTS: One hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5) vs 3.0 (0.3-6.2) mg/L, P = 0.003; adalimumab: 9.2 (6.5-12.0) vs 5.4 (2.5-8.3) mg/L, P = 0.004]. For patients on infliximab, fistula healing was associated with lower rates of detectable anti-infliximab antibodies and younger age. For patients on adalimumab, fistula healing was associated with higher rates of combination therapy with an immunomodulator. Serum trough levels for patients with and without fistula closure were not significantly different for infliximab [6.9 (4.3-10.2) vs 5.5 (2.5-8.3) mg/L, P = 0.105] or adalimumab [10.0 (6.6-12.0) vs 7.8 (4.2-10.0) mg/L, P = 0.083]. CONCLUSION: Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.

Safety, satisfaction and cost savings of accelerated infusions of standard and intensified-dose infliximab for inflammatory bowel disease.

BACKGROUND: Infliximab remains a mainstay for the treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and healthcare providers. AIMS: To assess the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings. METHODS: Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions: over 30 min if receiving a standard dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions. RESULTS: Fifty-two patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with a standard dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild and self-limiting. None required drug cessation. Patient satisfaction was improved with shortened infusion time as compared with the patients' previous experiences (P = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (±4.9) to 7.9 mg/L (±4.1) (P = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per patient per year for standard and dose-intensified infliximab respectively. CONCLUSION: Accelerated infliximab infusions for standard and dose-intensified regimens seem to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations.

Menetrier's disease exacerbating ulcerative colitis and relieved by gastrectomy.

Ménétrier's disease (MD) is a rare gastropathy characterised by giant rugal folds which can present with nausea, vomiting, abdominal pain and protein losing gastropathy. We report a 21-year-old woman with comorbid MD and ulcerative colitis (UC). Management was complicated by limited treatment options for MD, significant symptom burden, worsening nutrition and difficulty determining which disease was the predominant cause of symptoms. Since age 18 the patient experienced recurrent UC flares characterised by diarrhoea, persistent vomiting and corticosteroid dependence. Endoscopic assessment demonstrated concurrent MD and active UC. Octreotide and cetuximab were trialled given persistent hypoalbuminaemia and suspicion for MD associated protein-losing gastropathy. UC management comprised dose-optimised infliximab and methotrexate. Repeat endoscopic assessment demonstrated improvement in UC without corresponding improvement in symptoms or hypoalbuminaemia. Nasojejunal feeding and parenteral nutrition failed to significantly improve nutritional status and accordingly the patient proceeded to radical total gastrectomy. Postoperatively, MD-associated symptoms and hypoalbuminemia resolved completely.

Assessing effectiveness and patient perceptions of a novel electronic medical record for the management of inflammatory bowel disease.

BACKGROUND AND AIM: There is an increasing prevalence of chronic disease worldwide, resulting in multiple management challenges. Inflammatory bowel disease (IBD) is an exemplar chronic disease requiring coordinated longitudinal care. We propose that Crohn's Colitis Care (CCCare), a novel IBD-specific, structured electronic medical record is effective at improving data capture and is acceptable to patients. METHODS: A comparison was made between IBD-data completeness in usual records and CCCare. CCCare's acceptability to patients was assessed in two independent IBD patient cohorts and included:• Overall ratings of acceptability.• Factors associated with pre-exposure acceptability ratings.• Whether exposure and security concerns influenced acceptability ratings.• Direct patient feedback through CCCare's patient portal. RESULTS: In all cases reviewed, there was data gain using structured CCCare fields compared with IBD documentation in usual medical records. The overall acceptability in the combined cohort (n = 310) was very high. More than three-quarters of patients rated acceptability as >7 of 10. Self-reported information technology (IT) literacy positively associated with acceptability. Exposure had a small positive affect on acceptability, whereas security concerns had little impact on acceptability. Patient portal feedback revealed that most patients are very likely to recommend CCCare to others (8.56 ± 2.2 [out of 10]). CONCLUSION: CCCare is effective in supporting more complete IBD-specific data capture compared with usual medical records. It is highly acceptable to patients, especially those with reasonable IT literacy. Patient concerns about privacy and security of electronic medical records (EMRs) did not significantly affect acceptability.

The effect of a nurse-led advice line and virtual clinic on inflammatory bowel disease service delivery: an Australian study.

BACKGROUND: This retrospective cohort study investigated the economic impact of implementing a nurse-led inflammatory bowel disease (IBD) advice-line and virtual clinic on the Australian healthcare system. The advice line is a telephone and email service managed by IBD specialist nurses. The virtual clinic is a planned, formal communication between the gastroenterologist and the specialist IBD nurse the result of which is communicated to the patient electronically. METHODS: Advice line telephone calls and virtual clinic consultations registered between 1 June 2015 and 1 June 2016 were reviewed and analyzed in terms of outcome: avoidance of general practitioner (GP) consultation, IBD outpatient consultation, emergency department (ED) presentation, or hospital admission. Cost-benefit analysis was conducted to estimate financial savings. RESULTS: During the study period, 220 calls were received through the advice line and 1017 virtual clinic consultations occurred. The advice line resulted in the avoidance of 53 GP visits, 159 IBD outpatient department visits, six ED presentations, and one hospital admission. The virtual clinic resulted in the avoidance of four GP visits, 954 IBD outpatient department visits, and 58 ED presentations. This led to an estimated annual cost saving of AUD 169 376.80, with the annual costs incurred estimated to be $58 713. Thus, the annual net benefit of implementing the advice line and the virtual clinic was estimated to be $110 663.80. CONCLUSION: Specialized-IBD-nurse-led advice line and virtual clinic improves IBD patients' access to services and reduces healthcare costs. This highlights the importance of a proactive multidisciplinary approach in optimizing the care of patients with IBD.

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

INTRODUCTION: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.

Prospective single-blinded single-center randomized controlled trial of Prep Kit-C and Moviprep: Does underlying inflammatory bowel disease impact tolerability and efficacy?

BACKGROUND: Colonoscopy remains the gold standard for detection of colonic disease. An optimal evaluation depends on adequate bowel cleansing. Patients with inflammatory bowel disease (IBD), require frequent endoscopic assessment for both activity and dysplasia assessment. Two commonly used bowel preparations in Australia are Prep Kit-C (Pc) and Moviprep (Mp). Little is known about tolerability, efficacy and safety of split protocols of Mp and Pc in both IBD and non-IBD patients. AIM: To primary aim was to compare the tolerability, efficacy and safety of split protocols of Mp and Pc in patients having a colonoscopy. The secondary aim was to compare the efficacy, tolerability and safety of either preparation in patients with or without IBD. METHODS: Patients were randomized to Pc or Mp bowel preparation. Patients completed a questionnaire to assess tolerability. Efficacy was assessed using the Ottawa Bowel Preparation Score. Serum electrolytes and renal function were collected one week prior to colonoscopy and on the day of colonoscopy. RESULTS: Of 338 patients met the inclusion criteria. Of 168 patients randomized to Mp and 170 to Pc. The efficacy of bowel preparation (mean Ottawa Bowel Preparation Score) was similar between Mp (5.4 ± 2.4) and Pc (5.1 ± 2.1) (P = 0.3). Mean tolerability scores were similar in Mp (11.84 ± 5.4) and Pc (10.99 ± 5.2; P = 0.17). 125 patients had IBD (73 had Crohn's Disease and 52 had Ulcerative colitis). Sixty-four IBD patients were allocated to Mp and 61 to Pc. In non-IBD patients, 104 were allocated to Mp and 109 to Pc. The mean tolerability score in the IBD group was lower than the non-IBD group (mean tolerability scores: IBD: 10.3 ± 5.1 and non-IBD: 12.0 ± 5.3; P = 0.01). IBD patients described more abdominal pain with Mp when compared with Pc; (Mp: 5.7 ± 4.4 vs Pc: 3.6 ± 2.6, P = 0.046). Serum magnesium level increased with Pc compared with Mp in all patients (mean increase in mmol/L: Mp: 0.03 ± 0.117 and Pc: 0.11 ± 0.106; P < 0.0001). CONCLUSION: In this study, the efficacy, tolerability and safety of Mp and Pc were similar in all patients. However, patients with IBD reported lower tolerability with both preparations. Specifically, IBD patients had more abdominal pain with Mp. These results should be considered when recommending bowel preparation especially to IBD patients.

Management Decisions in Crohn's Disease Are Changed by Knowledge of Proactive and Reactive Testing of Antitumor Necrosis Factor Drug Levels.

Background: There is controversy about the proactive clinical application of therapeutic drug monitoring (TDM) of biologic drugs in Crohn's disease (CD). One way to practically assess this is to examine how TDM influences management decisions. We examined how knowledge of proactive and reactive antitumor necrosis factor (anti-TNF) drug levels changes management in a variety of clinical scenarios. Methods: In this retrospective cohort study, all adults with CD having trough level infliximab or adalimumab measurements at Liverpool Hospital between June 2013 and July 2016 were included. Demographics, indications for testing, anti-TNF drug levels, and treatment details were collected along with subsequent management decisions. The decision made by the treating clinician after receiving the drug level was compared to a consensus decision from a panel of 3 gastroenterologists based on the clinical, laboratory, imaging, and/or endoscopic results without the drug level. When these 2 decisions were discrepant, the anti-TNF drug level was deemed to have changed management. Results: One hundred and eighty-seven trough levels of infliximab or adalimumab from 108 patients were analyzed. Overall, assessment of anti-TNF levels affected management in 46.9% of the instances. Knowledge of the drug level was also more likely to result in management change when the test was performed for reactive TDM compared to proactive TDM (63% vs 36%, P = .001). Conclusions: The addition of TDM of anti-TNF agents to routine investigations alters management decisions in adult CD patients on anti-TNF therapy in both proactive and reactive settings.

Therapeutic drug monitoring in inflammatory bowel disease reduces unnecessary use of infliximab with substantial associated cost-savings.

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX) levels in inflammatory bowel disease (IBD) patients can help to guide dose adjustments or changes to therapy for selected patients in remission or with secondary loss of response (LOR). AIMS: To determine how IFX TDM is utilised in a real-life clinical setting and to quantify the potential for TDM to reduce the unnecessary use of IFX. METHODS: Data from all public IBD IFX level testing performed across Australia were prospectively collected from June 2016 to July 2017 to assess physician-reported for testing indications (induction, in remission or LOR) and associated results. The hypothetical influence of IFX TDM was based on an optimal therapeutic range of 6-10 mg/L for mucosal healing. RESULTS: Secondary LOR (reactive TDM) was the most common indication for TDM. These patients have consistently lower median IFX levels: 3.02 mg/L (IQR 1.14-6.67 mg/L) versus 5.22 mg/L (IQR 2.70-8.12 mg/L), P = 0.0001 compared with patients in remission (proactive TDM). TDM helped to identify unnecessary use of IFX in 30.6% of the TDM tests performed in luminal Crohn disease and ulcerative colitis patients, with an associated drug cost saving of $531.38 per IFX TDM test episode. Unnecessary IFX use was identified in 38.9% (96/247) of reactive IFX TDM tests performed and in 19.3% (35/181) of proactive testing. CONCLUSION: Use of both reactive and proactive IFX TDM is cost-effective for IBD management as it informs the clinician where unnecessary use of IFX can be stopped.

Comparative Evaluation of 4 Commercially Available ELISA Kits for Measuring Adalimumab and Anti-adalimumab Antibodies.

BACKGROUND: Therapeutic drug monitoring of tumor necrosis factor inhibitors, such as adalimumab (ADM), is increasingly being performed for the management of autoimmune diseases. However, there can be significant variation in drug and antibody concentrations obtained by different assay methods. The aim of this study was to compare the performance of 4 enzyme-linked immunosorbent assay (ELISA) kits for measuring ADM and anti-ADM antibodies. METHOD: Dilutions of ADM or anti-ADM spiked sera were assessed for recovery rate and precision using the following 4 kits: LISA-Tracker (Theradiag, Croissy-Beaubourg, France), Promonitor (Grifols, Barcelona, Spain), Ridascreen (R-Biopharm, Darmstadt, Germany), and Shikari (Matriks Biotek, Gölbasi/Ankara Turkey). Interference samples were also assessed. RESULTS: At the therapeutic concentration, ADM detection was comparable among the 4 ELISA kits. Lisa-Tracker and Shikari kits produced low-range false positive results in normal sera. Infliximab and etanercept caused false positives in Lisa-Tracker and Shikari kits. Anti-ADM antibody ELISA kits performed differently with spiked samples because of different measuring units and ranges. Ridascreen and Shikari kits were dose responsive across the entire standard curve and correlated well with each other (r = 0.997). Cross reactivity was observed in rheumatoid factor positive sera tested on the Promonitor anti-ADM kit. CONCLUSIONS: All ADM kits tested were dose responsive within the therapeutic range and correlated well. The significance of observed low-range false positives and cross reactivity with infliximab in LISA-Tracker and Shikari kits is dependent on the indications received for testing in the laboratory. Anti-ADM ELISA kits produced varied results for spiked sera; however, they showed good precision. Inter-kit variability suggested that anti-ADM levels should be compared only when using the same method.

Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy. METHODS: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n = 55), who in turn contributed to 21 multidonor batches (n = 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features. RESULTS: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT. CONCLUSIONS: In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635.

The need for better preventative strategies for inflammatory bowel disease patients at risk of herpes zoster virus.

BACKGROUND: Immunosuppressed inflammatory bowel disease (IBD) patients have an increased risk of herpes zoster virus (HZV) infection. The existing live-attenuated HZV vaccine is contraindicated in some of these patients and can only be used with caution in others. AIMS: To describe characteristics of IBD patients suffering HZV to enable implementation of risk mitigation strategies for those at highest risk. METHODS: Gastroenterologists completed a proforma for IBD patients who experienced HZV infection: IBD phenotype, details of HZV infection, immunosuppression and any change to treatment upon diagnosis of HZV. RESULTS: A total of 30 cases was identified: Crohn disease (CD) (n = 25) and ulcerative colitis (n = 5). In total, 80% (20/25) of the CD patients had penetrating, stricturing or perianal disease. Time from commencement of immunosuppression to HZV infection was highly variable (range: 3 months to over 10 years). A total of 90% (27/30) of patients was on at least one immunosuppressive therapy; of those, one-third was on monotherapy (9/27) and two-thirds (18/27) on dual therapy. A total of 89% (24/27) of immunosupressed patients was on a thiopurine (monotherapy; 6/27) or in combination (18/27). Complications of HZV occurred in 27% (8/30) of patients. CONCLUSION: Our series is consistent with existing epidemiological analysis that identified more severe IBD and the use of multiple immunosuppressive therapies as risk factors for HZV. If the promise of an investigational subunit HZV vaccine is realised in immunocompromised patients, better protection may be possible in the future. Thiopurine medications were the most commonly used immunosuppressant in this series. Age and duration of immunosuppressive therapy do not appear to predict HZV infection.

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

BACKGROUND: The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4-10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis. FINDINGS: From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1-11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission. INTERPRETATION: Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor-recipient matching based on microbial profiles. FUNDING: Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.

Comparison of infliximab drug measurement across three commercially available ELISA kits.

The monitoring of infliximab drug levels aids in the management of several autoimmune diseases, notably inflammatory bowel disease. Several commercial kits are now available and approved by the Therapeutic Goods Administration (TGA) for the measurement of infliximab levels, but there have been limited verification or comparison studies to date. Finding an assay that most accurately measures infliximab is essential for optimal drug titration and patient management. We performed this study to compare the performance of the Grifols Promonitor, Theradiag Lisatracker and R-Biopharm Ridascreen enzyme linked immunosorbent assay (ELISA) kits. Preparations of serum containing known concentrations of infliximab were assayed using each kit, including in the presence of interference from anti-infliximab antibodies, autoantibodies and other biological agents. The Lisatracker kit provided the most accurate determination of infliximab drug levels, however it yielded false positive results at low concentrations of infliximab. The average coefficients of variation (CVs) for the kits were 8% for Lisatracker, 5% for Ridascreen and 11% for Grifols. Infliximab measurements across all kits were affected by interference from antibodies to infliximab (ATI). This study identified the Lisatracker kit as the most accurate in quantifying infliximab levels, although it was limited by false positive results at low concentrations of infliximab as well as interference from ATI. This has important implications for the monitoring and management of patients receiving infliximab therapy.

Gastroenterologist perceptions of faecal microbiota transplantation.

AIM: To explore gastroenterologist perceptions towards and experience with faecal microbiota transplantation (FMT). METHODS: A questionnaire survey consisting of 17 questions was created to assess gastroenterologists' attitude towards and experience with FMT. This was anonymously distributed in hard copy format amongst attendees at gastroenterology meetings in Australia between October 2013 and April 2014. Basic descriptive statistical analyses were performed. RESULTS: Fifty-two clinicians participated. Twenty one percent had previously referred patients for FMT, 8% more than once. Ninety percent would refer patients with Clostridium difficile infection (CDI) for FMT if easily available, 37% for ulcerative colitis, 13% for Crohn's disease and 6% for irritable bowel syndrome. Six percent would not refer any indication, including recurrent CDI. Eighty-six percent would enroll patients in FMT clinical trials. Thirty-seven percent considered the optimal mode of FMT administration transcolonoscopic, 17% nasoduodenal, 13% enema and 8% oral capsule. The greatest concerns regarding FMT were: 42% lack of evidence, 12% infection risk, 10% non infectious adverse effects/lack of safety data, 10% aesthetic, 10% lack of efficacy, 4% disease exacerbation, and 2% inappropriate use; 6% had no concerns. Seventy seven percent believed there is a lack of accessibility while 52% had an interest in learning how to provide FMT. Only 6% offered FMT at their institution. CONCLUSION: Despite general enthusiasm, most gastroenterologists have limited experience with, or access to, FMT. The greatest concerns were lack of supportive evidence and safety issues. However a significant proportion would refer indications other than CDI for FMT despite insufficient evidence. These data provide guidance on where education and training are required.