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LINKED CONTENT: This article is linked to Danese et al papers. To view these articles, visit https://doi.org/10.1111/apt.16753 and https://doi.org/10.1111/apt.16761 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Danese et al papers. To view these articles, visit https://doi.org/10.1111/apt.16753 and https://doi.org/10.1111/apt.16795 [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Vuitton et al paper. To view this article visit https://doi.org/10.1111/apt.13948. [ABSTRACT FROM AUTHOR]

This article is linked to Eriksson et al papers. To view these articles visit https://doi.org/10.1111/apt.14268 and https://doi.org/10.1111/apt.14336. [ABSTRACT FROM AUTHOR]

Summary: Background: Escalation to anti‐tumour necrosis factor (anti‐TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing thiopurine at escalation is unclear. Aim: To assess the impact of discontinuing versus continuing thiopurine therapy at anti‐TNF initiation. Methods: We used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti‐TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti‐TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD‐related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: Of the 10,352 anti‐TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti‐TNF. After anti‐TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti‐TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10‐1.36), particularly for IBD‐related hospitalization (aHR: 1.14; 95% CI: 1.00‐1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13‐1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02‐1.34) and UC (aHR: 1.32; 95% CI: 1.12‐1.55). Conclusions: In a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti‐TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required. [ABSTRACT FROM AUTHOR]

Summary: Background: Increasing evidence supports the role of the gut microbiota in the aetiology of irritable bowel syndrome (IBS). Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridioides difficile infection in randomised controlled trials (RCTs), and may be beneficial in ulcerative colitis. However, its efficacy in IBS is uncertain. Aim: To perform a systematic review and meta‐analysis to examine this issue. Methods: We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through to March 2019. RCTs recruiting adults with IBS, which compared FMT with placebo, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI. Results: The search strategy identified 322 citations. Five RCTs were eligible for inclusion, containing 267 patients. Overall, 92.2% of included patients had IBS‐D or IBS‐M, and only 7.8% IBS‐C. When data were pooled for all patients, irrespective of stool type, the RR of IBS symptoms not improving was 0.98 (95% CI 0.58‐1.66). Placebo capsules administered orally were superior to capsules containing donor stool in two pooled trials (RR = 1.96; 95% CI 1.19‐3.20). FMT from donor stool delivered via colonoscopy was superior to autologous stool in two pooled RCTs (RR = 0.63; 95% CI 0.43‐0.93). FMT from donor stool via nasojejunal tube showed a trend towards a benefit over autologous stool in one trial (RR = 0.69; 95% CI 0.46‐1.02). Conclusions: Fresh or frozen donor stool delivered via colonoscopy or nasojejunal tube may be beneficial in IBS. Larger, more rigorously conducted trials of FMT in IBS are needed. [ABSTRACT FROM AUTHOR]

Summary: Background: Mesalazine is the most commonly prescribed medication for mild to moderate ulcerative colitis. It is generally well tolerated with some reported side effects. Aim: To summarise adverse drug events to mesalazine and recommend techniques for management. Furthermore, to determine if there is a dose‐dependent relationship between high (>2.4 g/day) vs low dosing (≤2.4 g/day) and occurrence of adverse drug events. Methods: A literature search for relevant studies from inception to 1 December 2017 of the MEDLINE database was conducted. Two reviewers screened all titles identified. Data obtained from randomised controlled trials was used to estimate incidence rates of each adverse event. Two reviewers independently assessed methodological risk of bias and performed data extraction. Results: 3581 articles were initially considered. Of these, 3573 were screened, 622 reviewed and 91 included. Adverse events attributed to mesalazine included inflammatory reactions, pancreatitis, cardiotoxicity, hepatotoxicity, musculoskeletal complaints, respiratory symptoms, nephropathies and sexual dysfunction. There does not appear to be a dose‐dependent relationship of mesalazine and occurrence of adverse events. Conclusion: Patients on mesalazine should be monitored for worsening of ulcerative colitis and development of new onset organ dysfunction. High‐dose mesalazine appears to have similar safety profile as low dose, and is not associated with greater risk of adverse events. Prior to placing a patient on mesalazine, baseline liver and renal function should be evaluated. Renal function should be periodically assessed, whereas other testing should be performed depending on development of symptoms. [ABSTRACT FROM AUTHOR]

Summary: Background: Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small‐molecule Janus kinase inhibitor, is potentially a new treatment option. Aim: To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. Methods: We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo‐controlled or head‐to‐head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate‐to‐severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk‐of‐bias. We used conventional meta‐analysis to synthesise direct evidence, and network meta‐analysis for adjusted indirect treatment comparisons. Results: Fifteen randomised, double‐blind, placebo‐controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36‐2.98) and golimumab (1.67, 1.08‐2.59) in clinical response, better than adalimumab (2.10, 1.21‐3.64) in clinical remission, and better than adalimumab (1.87, 1.26‐2.79) and golimumab (1.75, 1.13‐2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. Conclusions: Tofacitinib and biologics are efficacious and safe for UC. Further high‐quality research is warranted to establish the best therapeutic option. [ABSTRACT FROM AUTHOR]

Background Real-life long-term data on infliximab treatment in ulcerative colitis are limited. Aim To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. Methods A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Results Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) ( P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy ( HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. Conclusions Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy. [ABSTRACT FROM AUTHOR]

Background Acute severe ulcerative colitis is categorised using the Truelove & Witts criteria. The Travis and the Ho scores are calculated following 72 h of steroid treatment to identify patients at risk of failing steroid therapy who require colectomy or second-line medical therapy. Aim To compare the Travis and the Ho scores in a large unselected cohort to determine which might be more clinically relevant. Methods We analysed 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit of which 984 had acute severe ulcerative colitis. 420 patients had sufficient data for analysis. Patients were allocated into either a Travis high- or low-risk group and either a Ho high-, intermediate- or low-risk group. We assessed whether further medical or surgical intervention and outcomes varied between groups. Results High-risk patients in Travis and the Ho groups, when compared to lower risk groups, were more likely to fail steroid therapy: 64.5% (131/203) vs. 38.7% (84/217) ( P < 0.0001) for Travis and 66.2% (96/145) vs. 46.7% (85/182) vs. 36.6% (34/93) ( P < 0.0001) for Ho. They were also more likely to undergo surgery 34.0% (69/203) vs. 9.7% (21/217) for Travis and 33.1% (48/145) vs. 17.0% (31/182) vs. 11.8% (11/93) ( P < 0.0001) for Ho. Travis high patients were more likely to be refractory to second-line medical therapy: 44.6% (37/83) vs. 20.0% (9/45) ( P = 0.01). Conclusions Patients identified as high risk using the Travis or the Ho scoring systems are more likely to be resistant to IV steroids and require surgery. Risk of surgery in both high-risk populations is lower than previously reported. [ABSTRACT FROM AUTHOR]

Background The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis ( UC). Aim To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. Methods We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index ( CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. Results A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat ( P = 0.121) or per-protocol ( P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group ( P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. Conclusions The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. Eudra CT-Number 2007-007928-18. [ABSTRACT FROM AUTHOR]

Background Non-adherence to 5-aminosalicylic acid (5-ASA) medication can limit the established benefits of this therapy in ulcerative colitis (UC). Aim To determine rates and predictors of non-adherence to 5-ASA therapy in UC patients. Methods Medication adherence was assessed using self-report data and urinary drug excretion measurements. Participants completed a study-specific questionnaire and two validated questionnaires: Beliefs about Medicine Questionnaire (BMQ)-Specific and Satisfaction with Information about Medicines Scale. Results A total of 169 participants provided self-report adherence data; 151 also provided urine samples. Adherence rates were 111/151 (68%) according to self-report and 90/151 (60%) according to urine analysis, but the two measures were not correlated (χ2 = 0.12, P = 0.725). Logistic regression identified a significant association between self-reported non-adherence and younger age [odds ratio (OR) for increased age 0.954, 95% confidence interval (CI) 0.932–0.976] and also doubts about personal need for medication (OR for BMQ – Specific Necessity scores 0.578, 95% CI 0.366–0.913). For non-adherence based on urine analysis, only South Asian ethnicity was independently associated with non-adherence (OR 2.940, 95% CI 1.303–6.638). Conclusions Our observations confirm the difficulty of accurately assessing medication adherence. Nonmodifiable (younger age, South Asian ethnicity) and potentially modifiable (medication beliefs) predictors of non-adherence were identified. [ABSTRACT FROM AUTHOR]

Background Ulcerative colitis (UC) has a major impact on the quality of life (QoL) of affected patients. Patient-reported outcomes have not been thoroughly evaluated in patients with UC receiving oral mesalazine (mesalamine). Aim To examine the effect of mesalazine on QoL of patients with mildly and moderately active UC and assess the time course of change, baseline disease severity, mesalazine dose and responder status on QoL parameters. Methods Inflammatory Bowel Disease Questionnaire (IBDQ) data were combined from two double-blind, randomized, multicentre, active-controlled trials assessing 2.4 and 4.8 g/day oral delayed-release mesalazine in 687 patients. Mean score changes from baseline were compared at 3 and 6 weeks and effects of baseline severity, mesalazine dose and response to therapy were examined. Results Mesalazine significantly improved IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively; P < 0.0001 for both). Improvement was greater for patients with moderate disease. Greater week 6 changes occurred in clinical responders than nonresponders (50.1 vs. 23.6 points, respectively; P < 0.0001). Conclusions Delayed-release oral mesalazine produces significant clinical and statistical improvements in QoL of patients with UC by 3 weeks, with further improvement at 6 weeks. [ABSTRACT FROM AUTHOR]

Background Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. Aim To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Methods Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. Results 5-Aminosalicylic acids (5-ASA) remain the standard first-line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once-daily dosing, micropellet formulations, and high-dose tablets offer enhanced efficacy and improved compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ) and it has a role as a chemo-preventive agent in long-standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti-inflammatory targeted therapies include an anti-CD3 antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-γ agonists. Conclusion The evolution of novel oral 5-ASA formulations and dosage regimens, and recent development of new molecules have expanded the therapeutic armamentarium of UC. [ABSTRACT FROM AUTHOR]

Background More than two-thirds of ulcerative colitis patients experience at least one relapse over a period of 10 years. Treatments that reduce the likelihood of relapses also reduce the risk of long-term complications. Aim To review three topics: the current standard of treatment for ulcerative colitis, evolving concepts in treatment, and disease modification as a treatment goal of the future. Results Currently, 5-aminosalicylates are the standard treatment for the induction and maintenance of remission in mild-to-moderate ulcerative colitis patients. Evidence suggests that patients who take oral 5-aminosalicylates regularly are nearly six times more likely to experience regression in disease severity than those who do not. Additional treatment options such as corticosteroids, immunomodulators, biological therapies and ciclosporin are available for moderate-to-severe ulcerative colitis patients, or those who do not respond to 5-aminosalicylate. Surgery becomes pertinent for more than one-third of ulcerative colitis patients during the course of their disease. With the availability of a variety of therapies, advances in surgery and improved management strategies, a better understanding of patient treatment expectations can help improve the quality of care for ulcerative colitis patients. Conclusions Disease modification is increasingly becoming a treatment goal in the management of ulcerative colitis. However, long-term studies are needed to examine further the disease modifying role of 5-aminosalicylates. [ABSTRACT FROM AUTHOR]

Background Mesalazine is among the medications most commonly prescribed by gastroenterologists, having to a large extent superseded sulfasalazine (sulphasalazine). However, there are still a number of aspects regarding its use which provoke debate and controversy. Aim To provide a systematic assessment of the evidence for the use of mesalazine in ulcerative colitis and Crohn's disease. Methods References were identified using PubMed database. Additional references were identified with related article searches. Results Mesalazine has a clear role in the maintenance of remission in ulcerative colitis and management of mild to moderately active disease, although the efficacy of topical preparations or combined topical and oral is clearly superior to oral alone. Evidence that increasing the dose of oral mesalazine improves efficacy is not clear-cut. The benefits of mesalazine in the management of acute Crohn's disease and the maintenance of remission are questionable and alternative treatments are usually more appropriate. Emerging evidence suggests that maintenance mesalazine reduces the risk of neoplastic progression in chronic ulcerative colitis. Compliance with therapy is thus important, as is an understanding of individuals most likely to default on this. Conclusion Evidence for a beneficial effect of mesalazine is largely confined to the management of ulcerative colitis. [ABSTRACT FROM AUTHOR]

: The efficacy of azathioprine in the management of steroid-dependent ulcerative colitis is taken for granted. However, study populations frequently include together steroid-dependent and refractory patients. : To assess the efficacy and safety of thiopurinic immunomodulators in strictly defined steroid-dependent ulcerative colitis. : Survey of 34 patients with steroid-dependent ulcerative colitis, treated with azathioprine according to protocol. Therapeutical success: glucocorticoid withdrawal within 12 months, without steroid requirements during another year. : Mean age was 39.1 ± 17 years. Pancolitis and extensive colitis accounted for 50% of cases. Therapeutic success of immunomodulator treatment reached 70.6%, intention to treat analysis (confidence interval 95%: 52–84%) and 72.7%, as per protocol (confidence interval 95%: 54–86%). Mean time to steroid withdrawal was 4.6 months. In therapy successes, mean corpuscular volume and total serum bilirubin increased with treatment time ( P = 0.0001). Fifteen adverse effects were observed in 13 patients (38%). Azathioprine was withdrawn in seven cases (20.6%); in four of them (with liver toxicity), treatment with mercaptopurine was indicated. : Therapy with thiopurinic immunomodulators (azathioprine) represents the first option in the management of steroid-dependent ulcerative colitis. Its efficacy (70%) and its acceptable safety support this view. Increasing mean corpuscular volume and serum bilirubin values may be a surrogate marker of a beneficial effect. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient who was diagnosed with extensive ulcerative colitis in 2009 at the age of 23. Topics discussed include the use of azathioprine for treatment due to a corticosteroid-dependent course; the use of infliximab for treatment; and the anti-drug antibodies and subclinical inflammation detected in the patient.