Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.

BACKGROUND: Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). AIMS: This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC. METHODS: Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis. RESULTS: Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks. CONCLUSIONS: Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

Canadian association of gastroenterology clinical practice guideline for the management of Luminal Crohn's Disease

Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM: To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS: We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t-test (patients served as their own controls) ≤3 months before and 6-8 and 12-14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography. RESULTS: Use of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6-8 months (P = 0.03; mean change -70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12-14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6-8 or 12-14 months. CONCLUSIONS: Current evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

BACKGROUND: Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM: We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS: A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS: One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS: Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.

Comparison of infliximab with adalimumab in 827 biologic-naïve patients with Crohn's disease: a population-based Danish cohort study.

BACKGROUND: There are conflicting data on comparative effectiveness of adalimumab and infliximab in patients with Crohn's disease (CD). AIMS: To compare the effectiveness and safety of adalimumab and infliximab in biologic-naïve patients with CD, in a nationwide register-based propensity score-matched cohort study in Denmark. METHODS: A total of 2908 Danish adults with CD had been treated with adalimumab or infliximab as their first biologic agent between 2005-2014. By Cox regression, we compared rates of all-cause hospitalisation, CD-related hospitalisation, major abdominal surgery and serious infections after variable 2:1 propensity score matching, accounting for baseline disease characteristics, healthcare utilisation and use of CD-related medications. RESULTS: After propensity-score matching, we included 315 adalimumab- (34.9 ± 12.9 years, 41.9% males) and 512 infliximab-treated (33.6 ± 12.6 years, 40.8% males) patients, with median disease duration 4.0 years; 36.9% had prior abdominal surgery. Over a median follow-up 2.3 years after starting biological therapy, there were no significant differences in rate of CD-related hospitalisation (hazard ratio [HR], 0.81 [95% CI, 0.55-1.20]) or major abdominal surgery (HR, 1.24 [0.66-2.33]) between adalimumab- and infliximab-treated patients, though rate of all-cause hospitalisation was lower in adalimumab-treated patients (HR, 0.74 [0.56-0.97]). There was no significant difference in incidence of serious infections requiring hospitalisation (HR, 1.06 [0.26-4.21]). These results were stable in patients treated with biological monotherapy (all-cause hospitalisation: HR, 0.75 [0.53-1.05]; CD-related hospitalisation: HR, 0.82 [0.51-1.32], abdominal surgery: HR, 1.47 [0.63-3.47]) or in combination with immunomodulators (all-cause hospitalisation: HR, 0.70 [0.44-1.11]; CD-related hospitalisation: HR, 0.80 [0.42-1.52], abdominal surgery: HR, 1.02 [0.39-2.64]). CONCLUSIONS: In this population-based, propensity score matched, real-life cohort study using administrative claims, there was no significant difference in effectiveness and safety of adalimumab and infliximab in biologic-naïve patients with CD.

Immune modulator therapy for microscopic colitis in a case series of 73 patients.

BACKGROUND: Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. AIM: To evaluate the outcomes of patients with active MC treated with immune modulators. METHODS: All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded. RESULTS: Seventy-three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7-60) were included. The indications for treatment were budesonide-refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4-63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5-15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3-18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti-TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3-5.5). Complete response occurred in four patients and partial response in four patients. CONCLUSIONS: The majority of patients with active MC responded to thiopurines, methotrexate, or anti-TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC.

Comparative effectiveness and safety of infliximab and adalimumab in patients with ulcerative colitis.

BACKGROUND: Real-world comparative benefits and risks of infliximab (IFX) and adalimumab (ADA) in patients with ulcerative colitis (UC) are unclear. AIM: To evaluate the comparative effectiveness and safety of IFX and ADA in patients with UC who were new users of anti-TNF agents. METHODS: Using an administrative claims database (Optum Labs Data Warehouse), we identified patients who received first anti-TNF (IFX, ADA) prescription after a 12-month period without any anti-TNF treatment (baseline), and with a minimum 6-month follow-up after anti-TNF initiation. Primary outcome measures were: all-cause and UC-related hospitalisation, abdominal surgery, corticosteroid use >60 days after starting anti-TNF, and serious infections. We performed 2:1 propensity-score matched Cox proportional hazard analysis, and inverse probability-of-treatment weight (IPTW) analysis, accounting for healthcare utilisation, comorbidities and use of UC-related medication. RESULTS: We included 1400 new users of anti-TNF agents (age, 43 ± 15 years; 52% males), from 2006 to 2014. On propensity-score matched analysis, there was no significant difference in the risk of UC-related hospitalisation [IFX vs. ADA; adjusted hazard ratio (aHR), 1.04; 95% confidence interval (CI) 0.71-1.51], corticosteroid use (aHR, 0.85; 95% CI, 0.68-1.06) and serious infections (aHR, 0.62; 95% CI, 0.29-1.34) between IFX- and ADA-treated patients; the number of surgical events was very small. On IPTW analysis, risk of corticosteroid use was significantly lower in IFX - as compared to ADA - treated patients (aHR, 0.82; 95% CI, 0.68-0.99). Results were stable on multiple sensitivity analyses. CONCLUSIONS: In a large retrospective cohort of patients with UC who were new users of anti-TNF agents, IFX-treated patients may have lower corticosteroid use than ADA-treated patients, but risk of hospitalisation and serious infections were comparable.

Review article: recent advances in pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in inflammatory bowel disease.

BACKGROUND: Azathioprine and mercaptopurine have a pivotal role in the treatment of inflammatory bowel disease (IBD). However, because of their complex metabolism and potential toxicities, optimal use of biomarkers to predict adverse effects and therapeutic response is paramount. AIM: To provide a comprehensive review focused on pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in IBD. METHODS: A literature search up to July 2015 was performed in PubMed using a combination of relevant MeSH terms. RESULTS: Pre-treatment thiopurine S-methyltransferase typing plus measurement of 6-tioguanine nucleotides and 6-methylmercaptopurine ribonucleotides levels during treatment have emerged with key roles in facilitating safe and effective thiopurine therapy. Optimal use of these tools has been shown to reduce the risk of adverse effects by 3-7%, and to improve efficacy by 15-30%. For the introduction of aldehyde oxidase (AOX) into clinical practice, the association between AOX activity and AZA dose requirements should be positively confirmed. Inosine triphosphatase assessment associated with adverse effects also shows promise. Nucleoside diphosphate-linked moiety X-type motif 15 variants have been shown to predict myelotoxicity on thiopurines in East Asian patients. However, the impact of assessments of xanthine oxidase, glutathione S-transferase, hypoxanthine guanine phosphoribosyltransferase and inosine monophosphate dehydrogenase appears too low to favour incorporation into clinical practice. CONCLUSIONS: Measurement of thiopurine-related enzymes and metabolites reduces the risk of adverse effects and improves efficacy, and should be considered part of standard management. However, this approach will not predict or avoid all adverse effects, and careful clinical and laboratory monitoring of patients receiving thiopurines remains essential.

Systematic review with meta-analysis: faecal diversion for management of perianal Crohn's disease.

BACKGROUND: Temporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease (CD) with variable success. AIMS: To perform a systematic review with meta-analysis to evaluate the effectiveness, long-term outcomes and factors associated with success of temporary faecal diversion for perianal CD. METHODS: Through a systematic literature review through 15 July 2015, we identified 16 cohort studies (556 patients) reporting outcomes after temporary faecal diversion. We estimated pooled rates [with 95% confidence interval (CI)] of early clinical response, attempted and successful restoration of bowel continuity after temporary faecal diversion (without symptomatic relapse), and rates of re-diversion (in patients with attempted restoration) and proctectomy (with or without colectomy and end-ileostomy). We identified factors associated with successful restoration of bowel continuity. RESULTS: On meta-analysis, 63.8% (95% CI: 54.1-72.5) of patients had early clinical response after faecal diversion for refractory perianal CD. Restoration of bowel continuity was attempted in 34.5% (95% CI: 27.0-42.8) of patients, and was successful in only 16.6% (95% CI: 11.8-22.9). Of those in whom restoration was attempted, 26.5% (95% CI: 14.1-44.2) required re-diversion because of severe relapse. Overall, 41.6% (95% CI: 32.6-51.2) of patients required proctectomy after failure of temporary faecal diversion. There was no difference in the successful restoration of bowel continuity after temporary faecal diversion in the pre-biological or biological era (13.7% vs. 17.6%, P = 0.60), in part due to selection bias. Absence of rectal involvement was the most consistent factor associated with restoration of bowel continuity. CONCLUSIONS: Temporary faecal diversion may improve symptoms in approximately two-thirds of patients with refractory perianal Crohn's disease, but bowel restoration is successful in only 17% of patients.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study.

BACKGROUND: Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). AIM: To identify factors that influence long-term remission of CD with CZP treatment. METHODS: Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. RESULTS: Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. CONCLUSIONS: These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058).

Efficacy and safety of certolizumab pegol for Crohn's disease in clinical practice.

BACKGROUND: Certolizumab pegol (CZP) is Food and Drug Administration (FDA)-approved to treat Crohn's disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established. AIM: To report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6-year period since FDA-approval at a tertiary care centre. METHODS: All CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record-based review of steroid-free complete response (SCR), loss of response and safety. RESULTS: A total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9-24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5-59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75-12.61). Negative predictors included present perianal fistula (HR, 0.39; 95% CI, 0.16-0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04-0.76). Twenty-three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events. CONCLUSIONS: Certolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics-exposed patients. It may be more effective in patients without early-aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula.

Systematic review: colitis associated with anti-CTLA-4 therapy.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti-CTLA-4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune-related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common. AIMS: To discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti-CTLA-4-associated colitis, and to present a management algorithm for it. METHODS: We searched PubMed for studies published through October 2014 using the terms 'anti-CTLA,' 'ipilimumab,' 'tremelimumab,' 'colitis,' 'gastrointestinal,' 'immune-related adverse effect,' 'immunotherapy,' 'melanoma,' and 'diarrhoea.' RESULTS: Watery diarrhoea is commonly associated with anti-CTLA-4 therapy (27-54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8-22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti-CTLA-4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid-resistant cases may respond to anti-tumour necrosis factor-alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy. CONCLUSION: Given the increasing use of anti-CTLA-4 therapy, clinicians must be aware of related adverse events and their management.

Detection rate and outcome of colonic serrated epithelial changes in patients with ulcerative colitis or Crohn's colitis.

BACKGROUND: Chronic ulcerative colitis (CUC) and colonic Crohn's disease (CD) increase colorectal neoplasia (CRN) risk. While sessile serrated polyp (SSP) is a known cancer precursor, serrated epithelial changes (SEC) are of uncertain prevalence and neoplastic risk. AIM: To assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single-centre cohort study. METHODS: Patients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006-12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan-Meier method. RESULTS: Between 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010-12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0-30%) and 30% (3-57%), respectively, in SEC patients compared to 4% (0-12%) and 9% (0-23%), respectively, in CUC or CD controls (P = 0.047, log-rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia (P = 0.09). CONCLUSIONS: Serrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn's disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship.