Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease which requires regular gastroenterologist monitoring. Outpatient monitoring programs to date have focused on ...clinical scores alone, leaving patients with asymptomatic inflammation susceptible to undertreatment despite increased risk of flares and colorectal cancer. The University of Alberta IBD Unit developed and piloted an outreach and remote monitoring protocol for UC patients including clinical and biochemical variables. We assessed the effectiveness of this protocol at improving UC care. Aims This study aimed to develop a clinical outreach and remote patient monitoring protocol for UC patients and assess the impact this protocol had on disease management. Methods Biologic naïve adult UC patients who had not been reviewed by their gastroenterologist in at least six months were contacted by phone and mailed monitoring kits with Partial Mayo, Sutherland Index, and medication adherence questionnaires and a requisition for blood work and fecal calprotectin (FCP). Results were compiled and sent to each patient’s gastroenterologist. Participating gastroenterologists completed a survey about the perceived utility of the protocol and intended UC management changes. Results 85 patients completed the protocol. 86.4% of physician surveys rated the protocol as helpful to clinicians. UC management was changed in 55.6% of cases, with 82.2% of changes being management escalations. Six patients had active flares and 17 patients with asymptomatic inflammation were identified. Endoscopy was completed for 23 patients, with active disease observed in 78.2% of cases. Six patients started biologic therapies based on the protocol and endoscopic findings. UC management escalations were significantly predicted by FCP and Sutherland Index scores on logistic regression analysis. Conclusions This protocol had a meaningful impact on UC management and identified patients with active disease in both the presence and absence of clinical remission. Remote outpatient monitoring in UC should include collection of both FCP and clinical scores every six months to improve UC management. Funding Agencies None
Abstract
Background
There are limited data available on de-escalation of biological therapy after prior escalation in inflammatory bowel disease (IBD) patients. The aim of this study was to assess ...the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and evaluate which measures are used prior to de-escalation.
Methods
This multicentre, prospective, cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated at least once after prior biological escalation. Objective disease measures for de-escalation were defined as faecal calprotectin ≤ 200 µg/g and/or therapeutic or supratherapeutic trough levels and/or radiologic or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for ≥6 months after de-escalation.
Results
In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these, 34 (17%) patients on IFX, 18 (21%) patients on ADA and 8 (15%) patients on VEDO had received at least one subsequent de-escalation. De-escalation was successful in 91% of IFX patients, 89% of ADA patients and 100% of VEDO patients. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. De-escalation based on objective disease measures was performed in 67% of all de-escalations. Objective de-escalations were successful in 98% versus 80% of subjective de-escalations.
Conclusion
De-escalation after biological escalation is successful in the majority of patients. Objective markers of remission increase the likelihood of successful de-escalation.
Abstract Background Patients with inflammatory bowel disease (IBD) and concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia ...(CRN). Mucosal inflammation is an important driver of CRN development in IBD, but it is unknown whether this also applies to PSC-IBD patients. Aims We aimed to assess the impact of active mucosal inflammation per colonic segment and endoscopic remission on CRN risk. Methods This is a single-center case-control study, including cases with PSC-IBD with CRN, and controls with PSC-IBD without CRN. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and insufficient endoscopic follow-up (ampersand:003C2 available colonoscopy reports, and for cases, ampersand:003C2 available endoscopy reports before CRN diagnosis). Data was collected on demographics, IBD and PSC disease characteristics, and IBD medication use. Data from all available colonoscopy and sigmoidoscopy reports between 2002 and 2023, including endoscopic and histologic disease severity, disease extent, and CRN lesions, was collected. The primary outcome was a diagnosis of CRN, secondary outcomes included CRN grade and location, inflammatory burden per colonic segment harboring CRN, and colonic surgery. Results We included 247 PSC-IBD patients (163 ulcerative colitis, 80 Crohn’s disease) with a median follow-up of 6.3 years (IQR: 4.1-12.6) and 6 endoscopic procedures (IQR: 4.0-8.0). Median disease duration was 19 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-18.0). In 50 cases a total of 113 CRN lesions were observed, of which 11 (10%) were advanced CRN (aCRN; HGD or CRC). 23 patients (45%) were diagnosed with ampersand:003E 1 lesion while 45 lesions (40%) were identified in the right-sided colon, 27 (24%) in the transverse colon, 28 (25%) in the left-sided colon, and 10 (9%) in the rectum (3 lesions unknown). Endoscopic remission was observed in 24 cases (48%) during the 2 endoscopies prior to lesion detection vs. in 83 controls (42%) for their last 2 endoscopies. Of all CRN lesions, 39 (35%) were found in a colonic segment with confirmed previous endoscopic and/or histologic inflammation during the 1-2 endoscopies prior to lesion detection (31 low-grade and 8 aCRN). Of the 32 patients who underwent (sub)total colectomy or proctocolectomy, 20 (63%) had an indication due to CRN diagnosis. Mortality was 13% (n=32) during follow-up. Conclusions The risk for CRN and associated colectomy is high in PSC-IBD. Active mucosal inflammation preceded CRN in the affected colonic segment in only 35% of the lesions. Future expansion and additional analysis of our cohort will focus on the impact of persistent endoscopic remission and impact of biologic therapy on CRN risk in PSC-IBD. Funding Agencies None
Abstract
Background
The presence of serrated lesions (SLs) is an established risk factor for colorectal neoplasia development in the general population. However, the impact of SLs on the colorectal ...neoplasia risk in inflammatory bowel disease (IBD) patients is unknown. In addition, SLs might have been misclassified in IBD patients in the past, in part due to revisions of classification systems. Presently, SLs are categorised as hyperplastic lesions, sessile SLs, and traditional serrated adenomas. We aimed (1) to compare the colorectal neoplasia risk in IBD patients with SLs vs. IBD patients without SLs, and 2) to study the subclassification of SLs in IBD patients before and after histopathological review by two expert gastrointestinal pathologists.
Methods
We identified all IBD patients with colonic SLs from 1996 to 2019 in a tertiary referral centre using the local histopathology database. Patients with neoplasia prior to SL diagnosis were excluded. Clinical data from patients’ charts were retrieved until June 2019. A subgroup of 135 SLs was reviewed by two pathologists. The log-rank analysis was used to compare the cumulative (advanced) neoplasia incidence in IBD patients with SL vs. IBD patients without SL undergoing surveillance in the same time period. Patients were censored at the end of surveillance or at colectomy.
Results
We identified 376 SLs in 204 IBD patients (61.9% ulcerative colitis (UC)). In the original reports, 91.9% was classified as a hyperplastic lesion. After histopathological review, 120/136 (88%) of the SLs were confirmed (16 were no SL). Of the 120 confirmed SLs, 62.2% was classified as a sessile SL, 37.8% as a hyperplastic lesion, and 0.8% as a traditional serrated adenoma. The mean time from IBD diagnosis to the first serrated lesion was 14.3 ( ± 12.3) years. A total of 41/204 (20.0%) of patients developed neoplasia (3 CRC, 3 HGD, and 35 LGD; including 2 HGD and 17 LGD at the moment of serrated lesion detection). In the 304 patients without SL (52.6% UC), 63 developed neoplasia (20.7%; 8 CRC, 5 HGD and 50 LGD). Patients who received follow-up colonoscopies after SL (n = 127) had an increased cumulative risk of neoplasia (p < 0.01), but no increased risk of advanced neoplasia (p = 0.50) compared with the group of IBD patients without SL (Figure 1).
Conclusion
The presence of SLs in IBD patients was associated with a relatively high risk of synchronous colorectal neoplasia as well as an increased risk of subsequent neoplasia, although not with an increased risk of advanced neoplasia. Histopathological review confirmed the SL diagnosis in the majority of lesions, although a large proportion of the hyperplastic lesions was reclassified as a sessile SL.
Abstract
Background
To date, the association between vedolizumab (VDZ) serum concentrations and histological remission in ulcerative colitis (UC) has not been studied prospectively. VDZ serum ...concentrations could potentially offer additional guidance for predicting histological remission. We studied the relationship between VDZ serum concentrations and histological remission in a prospective study.
Methods
LOVE-UC was a multicentre international (Belgium, the Netherlands, and Hungary) open label prospective study in patients with moderately to severely active UC treated with VDZ. VDZ serum concentrations were measured at trough prior to every infusion. Endoscopy was performed at baseline, week 26 and 52. Biopsies from the most severely affected area and endoscopy videos were scored by blinded central readers. Histological remission was defined as a Robarts Histopathology Index <3 without neutrophils. Patients who did not undergo histological assessment were regarded as not having reached histological remission. Endoscopic remission was defined as a Mayo endoscopic sub-score 0.
Results
A total of 121 patients (61 male, 62 with prior exposure to tumour necrosis factor antagonists, mean total Mayo score at baseline of 9) received at least one infusion of VDZ. At week 26, 37.2% (45/121) patients were in histological remission, 38.8% (47/121) were in histological remission at week 52. The corresponding rates of combined histological and endoscopic remission were 19.8% (24/121) and 20.7% (25/121), respectively. Median VDZ serum concentrations were numerically higher at all time points in patients who achieved histological remission at week 26 than in those who did not (Table 1). Concentration thresholds (sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve) of 32.5 mg/L (66%, 68%, 54%, 74%, 0.681) at week 6 and 12.5 mg/L (76%, 60%, 61%, 70%, 0.724) at week 22 were associated with histological remission at week 26. Higher proportions of patients achieved histological remission at week 26 in higher VDZ serum concentration quartiles (Figure 1).
Conclusion
VDZ serum concentrations were positively associated with histological remission in UC, although the predictive value of serum concentrations for subsequent histological remission was modest.
Abstract
Background
Inflammatory bowel disease (IBD) patients with an ileo-anal pouch anastomosis (IPAA) bear an increased risk of pouch neoplasia, with prior colorectal neoplasia as the strongest ...predictor. It is unknown if pouch neoplasia develops independently or is derived from prior colorectal neoplasia.
Purpose
We aimed to assess potential clonality between prior colorectal neoplasia and pouch neoplasia in IPAA patients with IBD.
Method
In this explorative study we used the Dutch Nationwide Pathology Databank to identify IBD patients with both pouch neoplasia and colorectal neoplasia prior to colectomy. Clonality was assessed on colonic tissue of the lesion with shallow whole genome sequencing based copy number aberration (CNA) analysis and validated with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Result(s)
We included 13 patients who fulfilled the inclusion criteria. Three patients showed matching clonality CNA profiles between prior colorectal neoplasia and pouch neoplasia, validated with matching IHC and FISH for p19 and HER2. Patients with matching clonal samples also showed on retrospective review concordant histology of the neoplastic lesion pre- and post IPAA, positive resection margins, metastasized disease or a short interval (<2 years) between colorectal and pouch neoplasia diagnoses.
Image
Conclusion(s)
Three patients showed matching clonality patterns of neoplastic lesions, confirmed by clinical and histological data. Most pouch neoplasia in our cohort were molecularly different from their prior colorectal neoplasia. CNA provides a feasible method for clonality assessment in patients with colorectal neoplasia and subsequent pouch neoplasia.
Disclosure of Interest
None Declared
Abstract
Background
Thiopurine-treated inflammatory bowel disease (IBD) patients are monitored every 3 to 4 months with outpatient visits and laboratory assessments to evaluate disease activity and ...safety of therapy. However, the risk of thiopurine-related adverse events decreases after the initiation phase. The aim of this study was to assess the safety of reduced clinical monitoring in steroid-free quiescent IBD patients on stable maintenance thiopurine monotherapy.
Methods
This single-centre prospective cohort study evaluated a reduced monitoring strategy that involved 6-monthly laboratory assessment combined with alternating outpatient and phone appointments, during 104 weeks. We enrolled IBD patients who were in steroid-free remission > 6 months on thiopurine monotherapy including azathioprine, 6-mercaptopurine or tioguanine. The primary outcome was thiopurine-related adverse events (AE) requiring change or discontinuation of thiopurine therapy after 104 weeks of follow-up. Secondary outcomes were assessed at week 52 and included other thiopurine-related AEs and laboratory abnormalities.
Results
We included 85 patients (42 years median age, 61.2% Crohn’s disease, 62% female) with a median disease duration of 12.5 years. At baseline, 47 patients were treated with azathioprine (55.3%), 25 with 6-mercaptopurine (29.4%) and 13 with tioguanine (15.3%) for a median duration of 6.7 years. During 104 weeks of follow-up, thiopurine therapy was ceased in two patients because of multiple infections (n=1) and gastrointestinal complaints (n=1). Other reasons for thiopurine cessation (n=37) were stable remission (n=26), patient preferences (n=9) and high 6-TGN levels (n=2). In total, 20 patients underwent thiopurine dose adjustments due to high metabolite levels (n=9), remission (n=3), disease flare (n=3), patient preferences (n=3), and low metabolite levels (n=2). At 52 weeks, 27 laboratory abnormalities were observed, yet none required therapy adjustments. In 13 patients (15.3%) myelotoxicity was detected, including mild leukopenia (n=11), mild and moderate thrombopenia (n=2). In 16.5%, hepatoxicity was observed (n=14) including mild (n=9) and moderate (n=1) elevated aspartate aminotransferase and mild elevated alkaline phosphatase (n=4).
Conclusion
A reduced monitoring strategy appeared relatively safe in a strictly selected cohort of stable thiopurine-treated IBD patients. Overall, two patients had to cease thiopurine therapy due to thiopurine-related AEs independent of monitoring frequency. No laboratory abnormalities required therapy adjustments and 57.1% of patients continued therapy throughout 104 weeks of follow-up. This strategy may contribute to safe reduction of time and health care costs for both IBD patients and physicians in daily IBD practice.
Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of intestinal ischaemia. Previously described cases of MIVOD demonstrate vasculitis in mesenteric veins with thrombotic ...occlusion. It is important to distinguish MIVOD from other diseases, such as mesenteric venous thrombosis and systemic diseases. We present a case of a 39-year-old Turkish male in whom MIVOD was diagnosed after exclusion of other causes of ischaemic enteritis.
Abstract
Background
Prophylactic medication following ileocecal resection (ICR) is recommended in patients with Crohn’s disease (CD), particularly in patients at increased risk of recurrence. This ...study aimed to evaluate the effect of prophylactic medication on long-term prognosis.
Methods
A retrospective cohort study was performed in patients with CD who underwent a primary ICR. Patients were divided into two groups: prophylaxis (i.e. initiation of prophylactic medication<12 weeks following ICR) versus no prophylaxis. The primary and secondary outcomes were surgical recurrence and severe endoscopic recurrence (modified Rutgeerts score ≥ i3). To compare the outcomes between both groups, inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. The survival and association between prophylaxis and both outcomes were assessed with Kaplan-Meier analyses and Cox proportional hazard models.
Results
811 patients underwent an ICR median follow-up 5.8 years (IQR 2.5 – 10.7)(Table 1). Prophylaxis was initiated in 297/811 37% patients. In 364/514 71% patients without prophylaxis, medication was started after median follow-up 15 months IQR 7.2 – 46.5. Cumulative rates of surgical and endoscopic recurrence at 1, 2, 5 and 10 years were significantly lower in patients with prophylaxis versus no prophylaxis 1%, 3%, 9% and 19%, vs. 3%, 4%, 11% and 23%, p < 0.05 and 4%, 8%, 15% and 27% vs. 10%, 16%, 25% and 40%, p < 0.01. Propensity-scored weighted analysis showed that patients treated with prophylaxis were less likely to experience surgical recurrence aOR 0.52; 95% CI 0.33 – 0.82 and severe endoscopic recurrenceaOR 0.53; 95% CI 0.35 – 0.81. In multivariable analysis, prophylaxis was identified as protective factor for surgical aHR 0.67, 95% CI 0.45 – 0.99 and severe endoscopic recurrence aHR 0.54, 95% CI 0.37 – 0.78 (Table 2).
Conclusion
Surgical and severe endoscopic recurrence up to 10 years following primary ICR are significantly reduced in patients with CD who received prophylaxis as compared to no prophylaxis. Prophylaxis was associated with the prevention of surgical and severe endoscopic recurrence.
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