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.

Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission.

BACKGROUND AND AIMS: Outcomes of cessation of anti-TNF therapy for Crohn's disease (CD) in clinical and/or endoscopic remission in routine clinical practice is uncertain. This study aimed to evaluate clinical outcomes and factors associated with relapse in CD patients following formal disease assessment and elective anti-TNF withdrawal. METHODS: Prospective observational study of CD patients in whom anti-TNF therapy was stopped electively after ≥12months and follow-up of ≥6months. Investigations at assessment prior to cessation included ≥1 of clinical assessment, endoscopic and/or imaging. Relapse was defined as recurrent symptoms of CD requiring medical or surgical therapy. RESULTS: Eighty-six patients received anti-TNF for a median duration of 23 (12-80) months for severe active luminal (70%), fistulating perianal (25.5%) and other fistulating disease (4.5%). Relapse rates at 90,180 and 365days were 4.7%, 18.6% and 36%, respectively. If anti-TNF dose escalation occurred 6months prior to withdrawal, 88% (7/8) relapsed. Based on multivariate analysis, risk factors for relapse include ileocolonic disease at diagnosis and previous anti-TNF therapy. An elevated faecal calprotectin (FC) is likely to predict relapse (p=0.02), with a PPV of 66.7% at >50µg/g. Of 36 patients who relapsed, 31 were retreated with anti-TNF, with an overall recapture rate of 93%. CONCLUSION: Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.

The relationship between different information sources and disease-related patient knowledge and anxiety in patients with inflammatory bowel disease.

BACKGROUND: Patient education forms a cornerstone of management of inflammatory bowel disease (IBD). The Internet has opened new avenues for information gathering. AIM: To determine the relationship between different information sources and patient knowledge and anxiety in patients with IBD. METHODS: The use of information sources in patients with IBD was examined via questionnaire. Anxiety was assessed with the hospital anxiety and depression scale and disease-related patient knowledge with the Crohn's and colitis knowledge score questionnaires. Associations between these outcomes and demographics, disease-related factors, and use of different information sources were analysed using linear regression analysis. RESULTS: Of 307 patients (165 Crohn's disease, 142 ulcerative colitis) 60.6% were female. Participants used the hospital IBD team (82.3%), official leaflets (59.5%), and official websites (53.5%) most frequently in contrast to alternative health websites (9%). University education (P < 0.001), use of immunosuppressants (P = 0.025), Crohn's and Colitis UK membership (P = 0.001), frequent use of the hospital IBD team (P = 0.032), and frequent use of official information websites (P = 0.005) were associated with higher disease-related patient knowledge. Female sex (P = 0.004), clinically active disease (P < 0.001), frequent use of general practitioners (P = 0.014), alternative health websites (homoeopathy, nutritionists, etc.) (P = 0.004) and random links (P = 0.016) were independently associated with higher anxiety. CONCLUSIONS: Different patient information sources are associated with better knowledge or worse anxiety levels. Face-to-face education and written information materials remain the first line of patient education. Patients should be guided towards official information websites and warned about the association between the use of alternative health websites or random links and anxiety.

Efficacy and tolerability of methotrexate therapy for refractory Crohn's disease: a large single-centre experience.

BACKGROUND: Randomised controlled trials demonstrate that methotrexate is effective in inducing remission and preventing relapse of Crohn's disease (CD) as a first-line immunosuppressant, but efficacy data after failure with, or intolerance to, thiopurines are limited. AIMS: To report efficacy of methotrexate in a cohort of refractory CD patients, most of whom had not responded to, or were intolerant of, thiopurines. METHODS: Data were collected for patients receiving methotrexate for active CD. Response to methotrexate induction therapy at 4 months, and sustained clinical benefit at last point of follow-up with maintenance therapy, were assessed via physician's global assessment. Demographic and disease factors predicting response, or sustained clinical benefit, were examined by univariate and multivariate analysis. RESULTS: Sixty-six [38 (54%) female patients, mean age at diagnosis 29.4 years] patients received methotrexate between 2001 and 2010, 61 (92%) of whom received the drug parenterally. Sixty patients had failed, or were intolerant of, thiopurines. Response to therapy at 4 months occurred in 54 (82%) patients. However, sustained clinical benefit occurred in only 19 (29%) patients at last point of follow-up, including six patients who discontinued the drug for family planning reasons. No predictors of response or sustained clinical benefit were identified. Adverse events occurred in 20 (30%) patients. CONCLUSIONS: These data suggest that methotrexate is effective in terms of initial response in Crohn's disease patients who have failed, or are intolerant of, thiopurines. However, efficacy is not sustained in the long term.

Infliximab and surgical treatment of complex anal Crohn's disease.

AIM: Perianal fistulae in Crohn's disease are frequently complex, involve the anal sphincter complex and surgical treatment can be associated with poor healing of wounds and damage to the mechanism of continence. The aim of this study was to evaluate the efficacy and duration of response to infliximab in the long-term management of perianal fistulae in Crohn's disease in routine clinical practice. METHOD: A prospectively maintained database was used to identify patients with Crohn's disease and complex anal fistulae who were treated with infliximab (primary treatment, three initial infusions followed by maintenance therapy). Patients who received infliximab for luminal disease or for enterocutaneous, peristomal or rectovaginal fistulae were excluded from this study. RESULTS: Fifty-two patients [25 male, median age 24 (range 15-72) years] were treated with infliximab for perianal Crohn's fistulae for a median of 66 (7-124) months. Twenty-six of the patients underwent pre-infliximab MRI scans and 38 had an examination under anaesthetic (EUA) prior to commencement of treatment, 22 of whom had seton(s) inserted into their fistulae. Maintenance therapy was possible in 42 (81%) of 52 patients. Twenty-two (42.3%) patients had a complete response to treatment, 23 (44.2%) had a partial response and 7 (13.5%) had no response. Less than complete response to infliximab was associated with a greater risk of requiring surgical intervention (Fisher's exact test, d.f. 1, P = 0.005). CONCLUSION: The response rates of Crohn's related complex perianal fistulae to infliximab are good. Complete response is associated with a reduced need for surgical intervention.

Establishing a biologics service for patients with inflammatory bowel disease.

The use of anti-TNF therapy in the management of Crohn's disease and, to a lesser extent ulcerative colitis, is increasing. This article aims to discuss the practicalities of establishing a biologics service for patients with inflammatory bowel disease. Current guidelines on the use of these drugs are reviewed followed by a discussion on the choice of which anti-TNF agent to use based on costs and patient choice. A model for the initiation, administration, monitoring and assessment of patients receiving anti-TNF therapy is proposed. The need for a national biologics registry is highlighted in the summary.

Evidence-based use of anti-TNFα therapy in Crohn's disease; where are we in 2011?

The efficacy of anti-tumour necrosis factor (anti-TNFα) therapy with infliximab and adalimumab in moderate to severe Crohn's disease has now been proved. This article reviews the evidence supporting best practice with these agents in the light of recent National Institute for Health and Clinical Excellence guidance. Recent studies point to greater efficacy when these drugs are used early in the disease, particularly when mucosal healing can be achieved. For infliximab, the combination with immunomodulator drugs appears to afford greater efficacy, but possibly at the expense of the risk of rare but serious side effects. Patients should be selected carefully for treatment based on prognostic factors predicting aggressive disease, on the one hand, and comorbid factors that might predict side effects, on the other. Multiple drug combinations should be avoided where possible. Finally, a minority of patients in stable remission with complete mucosal healing may be selected for anti-TNFα drug withdrawal.

Systematic review: granulocyte/monocyte adsorptive apheresis for ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis (UC) that is chronically active despite 5-aminosalicylates or immunomodulators, or who are dependent on corticosteroids to maintain remission, have limited treatment options. Granulocyte/monocyte adsorptive apheresis (GMAA) may have a role in this situation. AIM: To conduct a systematic review of GMAA in UC. METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to identify randomized controlled trials (RCTs) comparing GMAA with conventional medical therapy, sham procedure or 'intensive' with 'conventional' GMAA regimens in adult UC patients. Studies reported clinical remission or response rates. RESULTS: Ten RCTs were eligible. Formal meta-analysis was not undertaken due to concerns about methodological quality of identified studies. Compared with medical therapy, remission rates with GMAA were generally higher, and corticosteroid-sparing effects were observed. Compared with sham procedure, GMAA did not achieve significantly higher remission rates. 'Intensive' GMAA regimens demonstrated generally higher remission rates, and time to remission was shorter compared with 'conventional' regimens. Only two RCTs were at low risk of bias. Six were conducted in Japanese patients, which may limit generalizability. CONCLUSIONS: Granulocyte/monocyte adsorptive apheresis appears of some benefit in UC. High-quality RCTs comparing granulocyte/monocyte adsorptive apheresis with conventional medical therapy or sham procedure in Western populations, with disease activity confirmed endoscopically, are required.

Costs of care for Crohn's disease following the introduction of infliximab: a single-centre UK experience.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in patients with Crohn's disease. There are few data, however, examining effect of infliximab therapy on management costs of Crohn's disease. AIM: To assess Crohn's disease-related costs of care and resource use in a single-centre cohort of patients with Crohn's disease 12 months pre- and post-infliximab therapy. METHODS: Data on 100 consecutive patients receiving infliximab were collected. Crohn's disease-related resource use was collected 12 months pre- and post-infliximab. National Health Service reference costs were applied to these data and the total Crohn's disease-related health service costs per patient were calculated (£UK). The cost of infliximab therapy was not included in our analysis. RESULTS: Cost savings were demonstrated in all areas of Crohn's disease-related resource use following infliximab therapy. Mean total Crohn's disease-related cost reduction, 12 months following commencement of infliximab therapy, was £2750 per patient. Mean costs at 12 months post-infliximab in responders were lower than in nonresponders (£1656 vs. £3608, P = 0.02). The number of hospitalizations was reduced. Requirements for examination under anaesthesia were also significantly decreased. CONCLUSION: Infliximab use resulted in Crohn's disease-related cost savings and hospital resource use, although this was not sufficient to cover the cost of therapy.

Anti-tumour necrosis factor-alpha therapies in Crohn's disease.

This article reviews the limitations of existing Crohn's disease therapies and the efficacy and safety of anti-tumour necrosis factor-alpha drugs. Trying to determine which patients may benefit from these therapies while minimizing toxicity is key. Special treatment situations and future developments are also briefly discussed.

Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse.

OBJECTIVES: An abnormal CD4+ T cell subset related to inflammation exposure (inflammation-related cells, IRC) has been identified in rheumatoid arthritis (RA). Patients with inflammatory and non-inflammatory diseases were used to examine the relationship between inflammation and this T cell subset in vivo. METHODS: Blood was collected from healthy controls and patients with RA (active disease or in clinical remission), Crohn's disease and osteoarthritis. IRC and chemokine receptors were quantified by flow cytometry. Thymic activity and apoptotic factors were measured by real-time polymerase chain reaction. Circulating cytokines were measured by enzyme-linked immunosorbent assay. CXCR4 and SDF1 in synovial biopsies were measured using immunohistochemistry. RESULTS: IRC were identified in patients with RA (p<0.0001) and Crohn's disease (p = 0.005), but not in those with osteoarthritis. In RA in remission, IRC persisted (p<0.001). In remission, hyperproliferation of IRC was lost, chemokine receptor expression was significantly lowered (p<0.007), Bax expression dropped significantly (p<0.001) and was inversely correlated with IRC (rho = -0.755, p = 0.03). High IRC frequency in remission was associated with relapse within 18 months (OR = 6.4, p<0.001) and a regression model predicted 72% of relapse. CONCLUSIONS: These results suggest a model in which, despite the lack of systemic inflammation, IRC persist in remission, indicating that IRC are an acquired feature of RA. They have, however, lost their hyper-responsiveness, acquired a potential for survival, and no longer express chemokine receptors. IRC persistence in remission confirms their important role in chronic inflammation as circulating precursors of pathogenic cells. This was further demonstrated by much higher incidence of relapse in patients with high IRC frequency in remission.

Mycophenolate mofetil therapy for refractory inflammatory bowel disease.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunomodulatory drug, and its use in inflammatory bowel disease has previously been reported. The aim of this study was to review the Leeds Colitis Clinic experience of the safety and efficacy of MMF in treating patients with refractory Crohn's disease (CD) and ulcerative colitis (UC). This is an extension of a previously published study from our center with a longer follow-up period and approximately twice the number of patients. METHODS: A retrospective analysis was performed of the records of all patients treated with MMF for inflammatory bowel disease over a 5-year period. RESULTS: Of 70 patients identified, 67 had previously been treated with azathioprine unsuccessfully. Seventeen of the 70 patients had been successfully maintained in remission with MMF for an average duration of 33 months. Treatment with MMF was discontinued for 53 patients, 17 because of side effects and 36 because they had not responded to the treatment. CONCLUSIONS: In our series, 17 patients (24.3%) had a sustained steroid-free remission with MMF therapy. Nineteen patients (27%) experienced side effects, of which 17 (24.3% of the total group) had to discontinue therapy. An additional 36 (51.4%) required an escalation in medical therapy or surgery because of failure of the MMF therapy. MMF may have a role in the treatment of refractory inflammatory bowel disease, especially in patients who have previously failed standard therapies such as azathioprine.