Background. Data regarding the correlation of histologic and endoscopic healing with fecal calprotectin (FC) are conflicting. We examined how FC levels correla

There is a paucity of evidence in ulcerative colitis [UC] comparing the traditional two-stage [total proctocolectomy with ileal pouch-anal anastomosis [IPAA] and diverting ileostomy, followed by ileostomy closure] vs the modified two-stage restorative proctocolectomy [subtotal colectomy with end ileostomy, followed by completion proctectomy and IPAA, without diverting ileostomy]. This study examines the risk of anastomotic leak following IPAA in traditional vs modified two-stage IPAA for UC patients. This was a single-institution, retrospective study of all UC patients who underwent a traditional or modified two-stage IPAA between 2002 and 2013. The primary outcome was anastomotic leak following IPAA. In all, 460 patients had a two-stage IPAA procedure; 223 [48.5%] patients underwent traditional two-stage IPAA and 237 [51.5%] patients received the modified two-stage procedure. There was more preoperative enteral corticosteroid use [44.7% vs 33.2%, p = 0.04] before the first surgery in the modified two-stage group compared with the traditional two-stage group. The modified two-stage group had higher UC disease severity at presentation [86.9% patients with moderate/severe UC vs 73.1%, p < 0.01]. However, the modified two-stage group had a lower rate of anastomotic leak following IPAA [4.6% vs 15.7%, p < 0.01] and was associated with a lower risk of anastomotic leak on univariate (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.13, 0.52] and multivariate analysis [OR 0.27, 95% CI 0.12, 0.57]. Patients with ulcerative colitis who received the modified two-stage IPAA had a significantly lower rate of anastomotic leak following pouch creation, compared with the traditional two-stage procedure.

Vedolizumab (VDZ) is an anti-integrin monoclonal antibody effective in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to examine the “real world” efficacy and safety of VDZ in a large national patient cohort. Patients with inflammatory bowel disease treated with VDZ were prospectively followed for 14 weeks. Patients who completed the induction protocol (week 0/2/6/14) or discontinued the treatment before week 14 for adverse events (AEs) or primary nonresponse were included. The primary outcome was induction of clinical remission at week 14; secondary outcomes included clinical response and corticosteroid-free clinical remission. A total of 204 patients (CD-130, UC-69, inflammatory bowel disease–unclassified-5) from 8 centers in Israel were included. Fifteen (7.4%) of the patients were anti–tumor necrosis factor naive and 46 (35.4%) had a previous surgery. For patients with CD, 69/130 (53.1%) responded to treatment; 45 (34.6%) achieved clinical remission; and 38 (29.2%) achieved corticosteroid-free remission at week 14. Fourteen (10.7%) patients discontinued VDZ before week 14 due to primary nonresponse or AEs. For UC, 32/74 (43.2%) responded to treatment; 20 (28.4%) achieved clinical remission, and 18 (24.3%) achieved corticosteroid-free remission at week 14. Fifteen (20.3%) patients with UC did not complete the induction due to primary nonresponse or AEs. AEs were reported by 29 (14.2%) patients (CD and UC combined), most common being nasopharyngitis and skin eruptions. In a large real-world Israeli cohort of anti–tumor necrosis factor–experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.

The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 µg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn’s disease (CD). A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey–Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay. Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl ( p = 6.93×10 ⁻⁶ ). Higher adalimumab trough level was significantly associated with MH (median 14.7 µg/mL in those with MH vs 3.4 µg/mL in those without, p = 6.25×10 ⁻⁵ ). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 µg/mL, p = 5.36×10 ⁻³ ). A cut-off of 8.14 µg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively). Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 μg/mL.

Background: The utility of fecal calprotectin (FC) in small intestinal Crohn's disease (CD) is unclear. We examined how reliably FC reflects clinical and mucosal disease activity in small intestinal CD, colonic CD, and ulcerative colitis (UC).Methods: A total of 72 Inflammatory Bowel Disease (IBD) patients (23 colonic CD, 14 isolated small intestinal CD, and 35 UC) were included. Clinical activity was assessed using the Harvey–Bradshaw Index (HBI) (CD) and Mayo score (UC). Inflammatory activity was assessed through ileocolonoscopy, cross‐sectional imaging, C‐reactive protein (CRP), and FC. Clinical activity was defined as HBI > 4 or Mayo clinical score ≥ 3. Endoscopy activity was defined as Mayo endoscopic subscore ≥ 1, SES‐CD score ≥ 3, and Rutgeerts > i1.Results: In UC, FC was correlated with the Mayo clinical score (P < 0.0001) and was highly correlated with the total Mayo score (P < 0.0001). A cut‐off value of FC 100 μg/g provided sensitivity of 88% and specificity 100% for endoscopic activity. FC was lower for patients with endoscopic and clinical remission compared to active endoscopic disease (median 100 vs 1180 μg/g, P < 0.0001). In colonic CD, there was a significant correlation between FC and endoscopic activity (P < 0.001). For an FC cut‐off value of 100 μg/g, sensitivity was 100%, and specificity was 67%. In contrast, for isolated small intestinal CD, there was no significant correlation between FC and objective disease activity measured by either endoscopy or imaging (AUC 0.52, P = 0.58).Conclusion: FC is reliable for the detection of colonic mucosal inflammation in both UC and CD but is less sensitive and reliable in the detection of small intestinal CD.

Summary: Background: Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited.Aim: To assess the effectiveness of dose escalation of ustekinumab.Methods: This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.Results: A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.Conclusions: Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.