Patrick B. Allen

Moving towards disease modification in inflammatory bowel disease therapy.

Purpose of review The inflammatory bowel diseases (IBDs) are chronic disabling conditions. Despite the benefits of anti-tumor necrosis factor (TNF)-&agr; agents in improving quality of life and reducing the need for surgeries, overall only one-third of patients are in clinical remission at 1 year and loss of response is frequent. It seems clear that treatment must go beyond alleviation of symptoms in IBD. It is important that treatment targets in IBD will ensure mucosal healing and deep remission. Recent findings The induction of deep remission might be the best way to alter the natural course of these diseases by preventing disability and bowel damage. New disability indices and the new Crohns disease damage score have recently been developed and they can be used to evaluate the long-term effect on patients and as new endpoints in trials. Early intervention with disease-modifying anti-IBD drugs (DMAIDs) should be considered in patients with poor prognostic factors. Summary New therapeutic targets in IBD patients who failed anti-TNF-&agr; therapy are urgently required, and tofacitinib, vedolizumab and ustekinumab appear to be the most promising drugs. Herein, we review the new and current trends in IBD therapy, with the final aim of changing disease course and patients’ lives by both improving quality of life and avoiding disability.

Does Anti-TNF Therapy Reduce the Requirement for Surgery in Ulcerative Colitis? A Systematic Review

Infliximab has demonstrated its efficacy in moderate to severe ulcerative colitis. The Active Ulcerative Colitis Trial (ACT) -1 and 2 have demonstrated the beneficial impact of infliximab on the short-term colectomy rate. However, data evaluating this outcome beyond one year remains scarce. To provide evidence on the potential impact of infliximab on the long-term colectomy rate in patients suffering from ulcerative colitis, data was reviewed from randomized and controlled studies, referral centre studies and population-based studies, in adult and pediatric populations. In the pre-biologic era, 9-33%, 50% and 29% of adult patients with ulcerative colitis underwent colectomy in clinical trials, referral center studies and population-based cohorts, respectively. In the pediatric population, 9-61% and 8-20% underwent colectomy in referral centers and population-based cohorts, respectively. Between 10 and 36% of adult patients treated with infliximab for ulcerative colitis underwent colectomy in clinical trials, referral center studies and population-based cohorts. In the pediatric population treated with infliximab, long-term data is lacking, with colectomy rates ranging from 16 to 28%. Whether infliximab proves to be a disease modifying treatment in ulcerative colitis in the long term remains to be elucidated and will require further long-term prospective studies.

Colorectal Cancer Risk Following Adenoma Removal: A Large Prospective Population-Based Cohort Study

Background: Randomized controlled trials have demonstrated significant reductions in colorectal cancer incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing colorectal cancer risk in routine clinical practice. The aim of this investigation was to quantify colorectal cancer risk following polypectomy in a large prospective population-based cohort study. Methods: Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland were identified via electronic pathology reports received to the Northern Ireland Cancer Registry. Patients were matched to the Northern Ireland Cancer Registry to detect colorectal cancer and deaths up to December 31, 2010. Colorectal cancer standardized incidence ratios (SIR) were calculated and Cox proportional hazards modeling applied to determine colorectal cancer risk. Results: During 44,724 person-years of follow-up, 193 colorectal cancer cases were diagnosed among 6,972 adenoma patients, representing an annual progression rate of 0.43%. Colorectal cancer risk was significantly elevated in patients who had an adenoma removed (SIR, 2.85; 95% CI, 2.61–3.25) compared with the general population. Male sex, older age, rectal site, and villous architecture were associated with an increased colorectal cancer risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess colorectal cancer risk. Conclusions: Colorectal cancer risk was elevated in individuals following polypectomy for adenoma, outside of screening programs. Impact: This finding emphasizes the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma. Cancer Epidemiol Biomarkers Prev; 24(9); 1373–80. ©2015 AACR.

EBV-associated colonic B-cell lymphoma following treatment with infliximab for IBD: a new problem?

Patients with inflammatory bowel disease who do not respond to steroid therapy often require treatment with immunomodulators in an attempt to achieve a response and maintain remission. However, a major concern and controversy is whether these treatments are putting the patients at a significantly increased risk of developing lymphomas. This case reports a patient with severe ulcerative colitis who had been previously treated with azathioprine and infliximab, and subsequently developed diffuse large B-cell colonic lymphoma.

Immunomodulators for the treatment of Crohn’s disease in adults: optimal use and prospects for future drug treatments

ABSTRACT Crohn’s disease (CD) requires treatment beyond symptoms by enabling and maintaining mucosal healing and therefore clinical remission. However, with the increasing use of biologics there have been safety concerns and there is a significant cost implication with the early use of biologics. Therefore, it is imperative that patients with severe/complicated disease or poor prognostic factors are treated with an aggressive strategy while all remaining patients should be treated in a step-up strategy. The potential for disease modification with thiopurines and methotrexate is debated in CD when they are used as a monotherapy. In this review we discuss existing and newer therapies that have recently been developed for CD. We will also provide an algorithm for current management of adult CD patients in routine clinical practice.

UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation

Background: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. Methods: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. Results: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1–77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [−77.0 (−96.3, −57.7); p < 0.001; n = 124] and baseline to 52 weeks [−70.7 (−95.0, −46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice.

Microscopic colitis: a population-based case series over a nine year period within Northern Ireland

We report clinicopathological experience of microscopic colitis (MC) in a population‐based case series in Northern Ireland over a 9‐year period.