Daniel R. van Langenberg

Functional gastrointestinal disorders in inflammatory bowel disease: Impact on quality of life and psychological status

Background and Aim:  In inflammatory bowel disease (IBD), ongoing gastrointestinal (GI) symptoms consistent with coexistent functional GI disorders (FGID) might occur. It is uncertain what effect these symptoms have on health‐related quality of life (HRQoL) and psychological comorbidity. The aim of the present study was to identify interrelationships among IBD, symptoms consistent with FGID, HRQoL, and psychological comorbidity.

Factors Associated with Physical and Cognitive Fatigue in Patients With Crohn's Disease: A Cross-sectional and Longitudinal Study

Background:Fatigue commonly impairs quality of life in patients with Crohns disease (CD). This study aimed to evaluate the prevalence and severity of fatigue in CD (compared with ulcerative colitis [UC] and healthy controls) and to identify potentially modifiable factors associated with global, physical, and cognitive dimensions of fatigue. Methods:Clinic attendees with confirmed CD or UC and healthy volunteers were surveyed on fatigue (Fatigue Impact Scale, FIS), psychological comorbidity, sleep quality, medication, and other clinical information. A CD subgroup also completed a similar follow-up survey. Results:In 379 responders (181 CD, 113 UC, and 85 controls), global, physical, and cognitive FIS scores were highest in CD followed by UC and controls (P < 0.01), with a prevalence of global fatigue (total FIS ≥ 40) in 57% of CD patients. On multivariate analysis, concurrently active disease, poor sleep quality, and mental illness were significantly associated with all the 3 fatigue dimensions: regular vitamin B group supplementation was inversely associated with physical fatigue in the CD cohort and those of older age or with previous resection(s) (P = 0.05) were independently associated with cognitive fatigue only. Longitudinally in CD, fatigue scores remained constant between original and follow-up surveys (mean change in total FIS score +0.9; 95% confidence interval, −4.6 to 6.3). Factors independently associated with improved physical fatigue between surveys included avoidance of corticosteroids and establishment of regular exercise and with improved cognitive fatigue included cessation of immunomodulator therapy. Conclusions:Fatigue is highly prevalent and more severe in CD. Anticipated and novel associations with improvement of physical and/or cognitive fatigue were identified, offering clues to potential therapeutic approaches to ameliorating fatigue for clinical evaluation.

Adverse clinical phenotype in inflammatory bowel disease: A cross sectional study identifying factors potentially amenable to change

Background and Aim:  A significant proportion with inflammatory bowel disease (IBD) exhibit an adverse clinical phenotype reflected in endpoints like surgery and hospitalizations. We sought to identify clinico‐demographic factors associated with these adverse consequences that may be amenable to change.

Cytomegalovirus disease, haemophagocytic syndrome, immunosuppression in patients with IBD: ‘A cocktail best avoided, not stirred’

We report two cases of cytomegalovirus (CMV) viraemia resulting in severe pneumonitis and associated haemophagocytic syndrome manifesting in patients with inflammatory bowel disease, on stable doses of azathioprine in clinical remission. In both cases, azathioprine was withdrawn at time of hospital presentation and after delays in diagnosis; intravenous ganciclovir was then administered, with resultant rapid improvement of haematological and clinical parameters. Following recovery, immunomodulators were not recommenced given patient aversion and the theoretical risk of CMV reactivation, albeit the evidence for this approach is limited. CMV-related haemophagocytic syndrome and organ dysfunction, in the context of immunomodulator therapy in IBD are rare but life-threatening, and thus requires further investigation and discussion.

Inflammatory bowel disease serology in Asia and the West

AIM To study serological antibodies in Caucasians and Asians, in health and inflammatory bowel disease (IBD), in Australia and Hong Kong (HK). METHODS Anti-glycan antibodies [anti-chitobioside (ACCA), anti-laminaribioside (ALCA)], and anti-mannobioside (AMCA), anti-Saccharomyces cervisiae (gASCA); and atypical perinuclear anti-neutrophil cytoplasmic antibody (pANCA) were tested in IBD patients, their unaffected relatives, and healthy controls in Australia and HK (China). Antibody status (positive or negative) and titre was compared between subjects of different geography, ethnicity and disease state. RESULTS Ninety subjects were evaluated: 21 Crohns disease (CD), 32 ulcerative colitis (UC), 29 healthy controls, and 8 IBD patient relatives. Forty eight subjects were Australian (29 Caucasian and 19 ethnic Han Chinese) and 42 were from HK (all Han Chinese). Caucasian CD patients had a significantly higher antibody prevalence of gASCA (67% vs 3%, P < 0.001), ALCA (44% vs 6%, P = 0.005), and AMCA (67% vs 15%, P = 0.002), whereas HK CD patients had a higher prevalence of only AMCA (58% vs 25%, P = 0.035), when compared with UC and healthy subjects in both countries. Caucasian CD had significantly higher gASCA prevalence (67% vs 0%, P < 0.001) and titre (median 59 vs 9, P = 0.002) than HK CD patients. Prevalence and titres of ALCA, ACCA and AMCA did not differ between CD in the two countries. Presence of at least one antibody was higher in Caucasian than HK CD patients (100% vs 58%, P = 0.045). pANCA did not differ between countries or ethnicity. CONCLUSION Serologic CD responses differ between HK Asian and Australian Caucasian patients. Different genetic, environmental or disease pathogenic factors may account for these differences.

Breath hydrogen response after lactulose does not predict symptom response to a probiotic fermented milk product in irritable bowel syndrome

Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics.

Poor predictive value of breath hydrogen response for probiotic effects in IBS.

Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics.

Satisfaction with patient-doctor relationships in inflammatory bowel diseases: Examining patient-initiated change of specialist

AIM To assess the reasons for, and factors associated with, patient-initiated changes in treating specialist in inflammatory bowel diseases (IBD). METHODS Prospectively identified IBD patients (n = 256) with ≥ 1 encounter at a metropolitan hospital were surveyed, including whether they had changed treating specialist and why. Negative reasons included loss of confidence, disagreement, and/or personality clash with the specialist. RESULTS Of 162 respondents, 70 (43%) had ever changed specialists; 30/70 (43%) for negative reasons, 52/70 (74%) in the preceding year. Patients with negative reasons for changing (n = 30) were younger (median, 35.2 years vs 45.3 years), had higher IBD knowledge (median, 5.0 years vs 4.0 years), yet had lower medication adherence and satisfaction scores (median, 19.0 years vs 22.0 years, 14.0 years vs 16.0 years respectively, Mann-Whitney tests, all P < 0.05), compared to all other responders (n = 132). Patients with a recent change (for any reason) were more likely to have Crohns disease, currently active disease, previous bowel resection and recent hospitalization [OR 2.6, 95% CI (1.3-5.4), 2.2 (1.0-4.7), 5.56 (1.92-16.67), 2.0 (1.3-3.0), each P < 0.05]. CONCLUSION Changing specialist appears associated with patient- related (age, nonadherence) and contemporaneous disease-related factors (recent relapse) which, where modifiable, may enhance patient-doctor relationships and therefore quality of care.

Anti-TNF Re-induction Is as Effective, Simpler, and Cheaper Compared With Dose Interval Shortening for Secondary Loss of Response in Crohn’s Disease

Background and Aims The optimal duration of dose-intensified therapy following secondary loss of response [LOR] to anti-tumour necrosis factor [TNF] therapy remains unclear. Anti-TNF re-induction involves a finite period of intensified therapy and may be a cost-effective means of re-capturing response. This study aimed to compare the efficacy, durability, and cost of anti-TNF re-induction and dose interval shortening [DIS] for secondary LOR in Crohns disease [CD]. Methods This was a retrospective observational study in CD patients who developed secondary LOR to maintenance anti-TNF therapy, requiring subsequent re-induction and/or DIS. The primary outcome was treatment failure within 12 months. Secondary outcomes included factors associated with time to failure, disease activity, and incremental anti-TNF costs. Results Of 423 patients with CD on anti-TNF therapy, 80 [19%] developed secondary LOR, with 33 and 55 patients undergoing subsequent anti-TNF re-induction and DIS, respectively. There was no significant difference in the incidence of treatment failure at 12 months following re-induction and DIS, respectively [p = 0.27]. Factors predictive of a longer time to failure included a higher baseline serum albumin, male sex, and thiopurine co-therapy [each p < 0.05], whereas higher baseline faecal calprotectin was associated with shorter time to failure. There was no significant difference in clinical remission or objective disease activity across both groups. The median incremental cost of re-induction and DIS was AUD 4 838 and AUD 13 190, respectively. Conclusions In patients with CD who develop secondary LOR, re-induction may represent an effective and less expensive first-line strategy, reserving dose intensification strategies such as DIS for non-responders.

Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told?

An awareness of the expected time for therapies to induce symptomatic improvement and remission is necessary for determining the timing of follow-up, disease (re)assessment, and the duration to persist with therapies, yet this is seldom reported as an outcome in clinical trials. In this review, we explore the time to clinical response and remission of current therapies for inflammatory bowel disease (IBD) as well as medication, patient and disease related factors that may influence the time to clinical response. It appears that the time to therapeutic response varies depending on the indication for therapy (Crohn’s disease or ulcerative colitis). Agents with the most rapid time to clinical response included corticosteroids, calcineurin inhibitors, exclusive enteral nutrition, aminosalicylates and anti-tumor necrosis factor therapy which will work in most patients within the first 2 mo. Vedolizumab, methotrexate and thiopurines had a longer time to clinical response and can take several months to achieve maximal efficacy. Factors affecting the time to clinical response of therapies included use of concomitant therapy, disease duration, smoking status, disease phenotype and advanced age. There appears to be marked variation in time to clinical response for therapies used in IBD which is further influenced by disease and patient related factors. Understanding the expected time to therapeutic response is integral to inform further decision making, maintain a patient-centered approach and ensure treatment is given an appropriate timeframe to achieve maximal benefit prior to cessation.