Ruben J. Colman

Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis

BACKGROUND AND AIMS Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD. METHODS A systematic literature search was performed through May 2014. Inclusion criteria required FMT as the primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections. RESULTS Eighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included. 122 patients were described (79 ulcerative colitis (UC); 39 Crohns disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow-up. Among the cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%-60.4%), with a moderate risk of heterogeneity (Cochrans Q, P=0.011; I(2)=37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%-40.8%) for UC (P=0.37; I(2)=0%) and 60.5% (95% CI 28.4%-85.6%) for CD (P=0.05; I(2)=37%). Six studies performed microbiota analysis. CONCLUSIONS This analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.

Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review

Background/Aims Ulcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed. We performed a systematic review and meta-analysis to explore the relationship between histologic inflammation and risk for neoplasia among available observational studies. Methods Three databases (EMBASE, MEDLINE and the Cochrane Library) were systematically searched. Studies were included if they included UC patients who underwent colonoscopic assessment and when histologic inflammation and colorectal neoplasia were both reported. Colorectal neoplasia rates were compared. Quantitative meta-analysis was attempted. Results Four of 1,422 records found were eligible. Results from 2 case-control studies reported a 3.5-fold increased risk for colorectal neoplasia associated with a single point increase in histologic inflammation. This result was further corroborated by one cohort study that demonstrated increased hazard ratios. The second cohort study reported outcomes for patients with normal gross endoscopy, but had increased histological inflammation when neoplasia was assessed. Finally, this study reported increased risk for neoplastic progression by histological inflammation among patients who were normal by gross endoscopic evaluation. Quantitative meta-analysis was unsuccessful due to heterogeneity between study measures. Conclusions There is strong evidence that histologic inflammation among patients with UC increases the risk of colorectal neoplasia. The depth and nature of assessment of additional clinical variables was varied and may have resulted in greater outcome discrepancy. Additional study related to mechanisms of inflammation-related neoplasia and therapeutic modification is needed.

Optimal Doses of Methotrexate Combined with Anti-TNF Therapy to Maintain Clinical Remission in Inflammatory Bowel Disease

BACKGROUND AND AIMS Methotrexate (MTX) is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease [IBD]; however, the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower-dose and higher-dose MTX with anti tumor necrosis factor alpha (anti-TNF) therapy among IBD patients. METHODS Retrospective chart review was performed of 88 IBD patients at our center between 2010 and 2013. Low-dose MTX was defined as ≤ 12.5mg/week and high-dose MTX as 15-25mg/week. Patients who met the criteria for clinical remission [Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2] at baseline were followed for up to 42 months. Chart review occurred in 6-month intervals. The primary outcome was consecutive months in remission prior to relapse. Secondary outcomes included other indicators of worsening disease [endoscopic inflammation, steroid use, therapy escalation/addition, or surgery] and adverse events. Regression analysis and Kaplan-Meier survival analysis were completed. RESULTS We identified 73 [83%] dual-therapy patients, of whom 32 low-dose and 14 high-dose individuals achieved remission. When compared with high-dose patients, low-dose patients were more likely to relapse [log-rank test, p < 0.01]. Secondary indicators of worsening disease occurred during 34.4% of low-dose review periods and 31.4% of high-dose review periods [p = 0.67]; 3/52 [6%] low-dose patients and 3/21 [14%] high-dose patients [p = 0.34] discontinued MTX therapy due to adverse events. CONCLUSIONS When combined with anti-TNF therapy, MTX at doses of >12.5mg/week was more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients.

Surveillance of IBD Using High Definition Colonoscopes Does Not Miss Adenocarcinoma in Patients with Low-grade Dysplasia.

Background:Historically, limits to the ability to detect dysplasia in chronic inflammatory bowel disease (IBD)-associated colitis resulted in the recommendation that neoplasia of any grade be treated by proctocolectomy. We hypothesized that with improved optical technologies, most neoplasia in colitis is now detectable and reassessed the prevalence of colitis-associated neoplasia. Methods:We retrospectively reviewed all our patients with IBD who had pathologist-confirmed neoplasia on surveillance colonoscopy and underwent a subsequent colectomy. We included patients whose index lesions were found between 2005 and 2014 (the dates of our high definition equipment) and recorded the location and grade of these lesions. These findings were compared to the surgical specimens, and in patients with partial colectomies, included follow-up. Results:Thirty-six patients with IBD (19 [53%] ulcerative colitis and 17 [47%] Crohns disease) were found to have neoplastic lesions on surveillance colonoscopy and underwent a subsequent partial colectomy or total proctocolectomy. Forty-four index lesions were identified by colonoscopy (29 white light and 7 methylene blue chromoscopy): 30 low-grade dysplasia, 6 high-grade dysplasia, and 8 adenocarcinoma. None of the low-grade dysplasia or adenocarcinoma index lesions were associated with synchronous carcinoma at colectomy. One of the patients with high-grade dysplasia had adenocarcinoma of the appendix. Conclusions:In this experience with high definition colonoscopes in chronic colitis, no synchronous adenocarcinomas were found when colectomy was performed for low-grade dysplasia or index adenocarcinoma, and only 1 adenocarcinoma in the appendix was found in the setting of high-grade dysplasia. These findings suggest that active surveillance or subtotal colectomy may be safe options for patients with IBD and some grades of neoplasia.

Tu1350 Vedolizumab in the Treatment of IBD: The University of Chicago Experience

G A A b st ra ct s multicentre, observational cohort was designed to examine the safety and efficacy of CTP13 infliximab biosimilar in induction and maintenance of remission in Crohns disease (CD, 108 weeks follow-up) and ulcerative colitis (UC, 54 weeks follow-up). Demographic data were prospectively collected at inclusion. A harmonized, tight monitoring strategy is applied in terms of clinical scores (CDAI, PDAI, pMAYO at each visit), biochemical markers (including CRP, at least every 3 months) and endoscopic/imaging (at least every 12 months) as requested by the National Health Fund. Sera are collected for drug through and antibody measurement at 0, 12, 24 and 52 weeks. Safety data are meticulously registered during follow-up. Results: 90 consecutive IBD patients were included in the present cohort (57 CD patients (27 males) and 33 UC patients (16 males)). Age at disease onset was 26.0 (SD:10.9) years in CD and 30.5 (SD:14.1) years in UC. In CD ileocolonic and perianal disease was present in 40.4% and 37.5% of patients, respectively. 55.2% of UC patients had extensive colitis. 21.4% of CD patients had previous surgery. In CD and UC, 60.4%/ 50% and 55.2%/74.2% of patients received concomitant immunosuppressives and steroids, while 30.4% of CD and 16.1% of UC patients received previous anti-TNFs. At induction, mean CDAI was 289 (SD:107), while MAYO/pMAYO scores were 8.8 (SD 3.1) and 6.4 (SD 2.6) in UC. There was a significant decrease in CDAI after 2 and 6 weeks of treatment compared to baseline (p<0.001, ANOVA-Scheffe). In addition there was a numeric decrease in the mean CRP level (from 23.5mg/L to W2:11.3mg/L and W6:15.3mg/L). There was a significant decrease also in the mean pMAYO score (from 6.4 to (n=16) W2: 3.7 and W6: 3.6) with a numeric decrease in CRP level during induction therapy in UC . 4 allergic reactions occurred, all in patients who had received previous anti-TNF medication. Conclusions: This is the first prospective nationwide cohort examining the safety and efficacy of the biosimilar infliximab in IBD. A significant decrease of disease activity (CDAI and pMAYO) was observed coupled with a decrease in CRP levels during induction with the infliximab biosimilar. A complete analysis of the induction data will be available at the time of congress.

Successful Treatment of Ulcerative Colitis With Vedolizumab in a Patient With an Infliximab-Associated Psoriasiform Rash.

Psoriatic skin lesions associated with anti-tumor necrosis factor (TNF) agents are well-described in the medical literature. However, the etiology and optimal management of this condition remain unclear. Vedolizumab is a novel, gut-specific, anti-integrin agent used for the treatment of inflammatory bowel disease (IBD). We report a case of infliximab-associated psoriasiform lesions in an ulcerative colitis patient. Transition to vedolizumab resulted in resolution of the cutaneous lesions without recurrence and remission of his ulcerative colitis.

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety

Background Vedolizumab is approved for moderate to severe Crohns disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease. Methods Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included. Patients had clinical activity scores (Harvey-Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]) and inflammatory markers prospectively measured at baseline and weeks 14, 30, and 52. Clinical response was defined as a reduction ≥3 in HBI or SCCAI, clinical remission as HBI ≤4 or SCCAI ≤2, steroid-free remission as clinical remission without the need for corticosteroids, and mucosal healing (assessed at 6 months) as a Mayo endoscopic subscore of 0 or 1 or CD-SES <3. Results A total of 132 patients were included: 61 (45%) male, 94 (71%) with CD, 42 (29%) with UC; 22% and 34% of CD and UC patients, respectively, achieved steroid-free remission by week 14. This increased to 31% in CD patients and plateaued at 35% in UC patients at 12 months. Increasing remission rates to 6 months were seen in patients with CD, but minimal improvements after 3 months of therapy occurred in those with UC. Mucosal healing was achieved in 52% of UC and 30% of CD patients. Most adverse events were minor; 74% remained on vedolizumab at 12 months. Conclusions In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067_video1izx067_Video5754037470001.

Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease

Background & Aims Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohns disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors. Methods We collected data on patients with CD (n = 9) or UC (n = 11) who began treatment with vedolizumab from May 20, 2014, through March 30, 2015, and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey–Bradshaw index score ≤4 or short clinical colitis activity index score ≤2; steroid‐free clinical remission was defined as clinical remission without corticosteroids. Results By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid‐free clinical remission; after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid‐free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary nonresponse to vedolizumab—1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid‐free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors. Conclusions Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow‐up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.

Prevalence of functional GI disorders among pediatric patients with persistent asthma: Functional GI disorders and asthma

Functional gastrointestinal (GI) disorders (FGIDs), such as irritable bowel syndrome, functional abdominal pain and dyspepsia, are common causes of chronic GI symptoms in children. Prior studies found high comorbidity of FGID and asthma. This study aimed to assess the prevalence and comorbidities of FGID among pediatric patients with asthma at a university‐affiliated urban community hospital.

Efficacy and Follow-Up of Subtotal Colectomy With Ileorectal Anastomoses in Patients With Colitis-Associated Neoplasia

&NA; The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1–3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.4–6 We hypothesized that if a lesion was completely removed surgically and followed up endoscopically, metachronous colorectal carcinoma would be a rare occurrence. Thus, segmental resection may be offered as a definitive surgery in patients with chronic colitis and localized colorectal neoplasia in whom endoscopic resection is not feasible. Retention of the distal colon/rectum is expected to result in an overall improved quality of life compared with permanent ileostomy or an ileoanal J‐pouch. Here, we report our experience and follow‐up evaluation of segmental resections for preoperative neoplasia in patients with Crohns disease (CD) or ulcerative colitis (UC).