CD-related Complications Research Articles

Role of capsule endoscopy and double-balloon enteroscopy in the management of adult patients with coeliac disease and persisting symptoms

BackgroundSmall bowel capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are recommended for the management of patients with nonresponsive or refractory coeliac disease (CD). However, there is a paucity of data regarding the clinical profiles and outcomes of patients undergoing these investigations. MethodsWe conducted a retrospective analysis of two databases of adult patients with CD who underwent CE and/or DBE between 2017 and 2022 at the National Centre for Refractory CD in England. Patient demographic, clinical and endoscopic data were collected, and clinically relevant outcomes were reported. ResultsA total of 132 patients (median age 53 years, 64.4 % female) underwent 146 CEs and 25 DBEs. The most common symptoms were diarrhoea (51.5 %), abdominal pain (37.8 %), bloating (34.8 %), and weight loss (29.5 %). The overall detection rate of CE and DBE was 87.6 % and 92 %, respectively. Following CE and DBE, 14 patients (10.6 %) were diagnosed with CD-related complications such as ulcerative jejunitis, strictures and malignancy. Seven patients (5.3 %) died during follow-up, with five of these deaths directly attributed to CD. Older age, weight loss and anaemia were associated with poor outcomes. ConclusionsThe sequential approach of CE and DBE identified CD-related complications in almost 1 in 10 patients with nonresponsive or refractory CD. Older patients with persistent villous atrophy, weight loss and anaemia require close monitoring to help with the early diagnosis and management of complications.

P643 Magnifying Endoscopy with Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients with Crohn’s Disease after Intestinal Transplantation

Abstract Background Crohn’s disease (CD) is one of the common causes of short bowel syndrome (SBS) and intestinal failure (IF). Intestinal transplantation (IT) is sometimes needed for patients with CD who develop IF after multiple intestinal resections due to CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been limited case reports concerning the endoscopic surveillance of CD patients after IT. Methods We retrospectively investigated two patients with CD who underwent IT because of SBS-IF after multiple intestinal resection. We administered post-transplantation immunosuppressants and conducted regular magnifying endoscopy with narrow-band imaging (ME-NBI) via ileostomy chimney for surveillance of grafte rejection. Endoscopic prediction of rejection were based on our previously published "VENCH" score which is composed of five parameters: "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). Endoscopic biopsy were taken for histologic confirmation of graft rejection severity. Results Case 1 was a 60-year-old male patient with CD who received three times of intestinal resection for small bowel stricture and perforation, followed by IT due to SBS-IF. He lived uneventful until seven years thereafter with bloody diarrhea presented. Endoscopic surveillance revealed normal VENCH score of background mucosa but deep longitudinal ulcers which was indicative of recurrence of CD rather than graft rejection. Anti-tumor necrosis factor alpha with adalimumab was prescribed and his diarrhea and graft ulcers improved. Case 2 was a 39-year-old male patient with CD who received extensive intestinal resection due to multiple perforations, followed by IT because of SBS-IF. Endoscopic surveillance revealed normal VENCH score without histologic graft rejection two years thereafter. Both enrolled cases demonstrated favorable outcomes after endoscopic surveillance of intestinal graft with ME-NBI and management accordingly. Conclusion The post IT follow-up of CD patients remains challenging. We highlight the usefulness of the ME-NBI using VENCH score for early detection of graft rejection and its value in monitoring CD patients after IT. Additionally, ulcerations without changes in morphology of surrounding villi should take into consideration the disease recurrence of underlying CD. Further research is needed in endoscopic follow-up and molecular genetics to better understand CD after IT.

Early intervention with biologic therapy in Crohn´s disease: how early is early?

Early biologic therapy within the first 18-24 months after diagnosis is associated with improved clinical outcomes in Crohn's disease [CD]. However, the definition of the best time to initiate biologic therapy remains unclear. We aimed to assess if there is an optimal timing for early biologic therapy initiation. This was a multicentre retrospective cohort study including newly diagnosed CD patients who started anti-tumour necrosis factor [TNF] therapy within 24 months from diagnosis. The timing of initiation of biologic therapy was categorised as ≤6, 7-12, 13-18, and 19-24 months. The primary outcome was CD-related complications defined as a composite of progression of Montreal disease behaviour, CD-related hospitalisations, or CD-related intestinal surgeries. Secondary outcomes included clinical, laboratory, endoscopic, and transmural remission. We included 141 patients where 54%, 26%, 11%, and 9% started biologic therapy at ≤6, 7-12, 13-18, and 19-24 months after diagnosis, respectively. A total of 34 patients [24%] reached the primary outcome: 8% had progression of disease behaviour, 15% were hospitalised, and 9% required surgery. There was no difference in the time to a CD-related complication according to the time of initiation of biologic therapy within the first 24 months. Clinical, endoscopic, and transmural remission was achieved in 85%, 50%, and 29%, respectively, but no differences were found according to the time of initiation of biologic therapy. Starting anti-TNF therapy within the first 24 months after diagnosis was associated with a low rate of CD-related complications and high rates of clinical and endoscopic remission, although we found no differences with earlier initiation within this window of opportunity.

Economic burden related to fistulas or strictures among commercially insured patients with Crohn's disease in the United States.

BACKGROUND: Crohn's disease (CD) is a chronic, progressive, immune-mediated gastrointestinal condition that can lead to fistulizing or stricturing complications. OBJECTIVE: To quantify the burden of illness related to fistulas and/or strictures in patients with CD. METHODS: Using the Optum Research Database from October 2015 to December 2019, patients with CD were classified according to 1 of 3 condition cohorts: CD with fistula (CD-F), CD with stricture (CD-S), or CD with fistula and stricture (CD-FS). Each cohort was matched to a nonfistula, nonstricture CD cohort. Postdiagnosis per patient per year (PPPY) costs and health care resource utilization were assessed, accounting for variable lengths of follow-up periods. Multivariable generalized linear models were used to estimate the adjusted mean costs in each cohort. RESULTS: The CD-F, CD-S, and CD-FS cohorts included 1,317; 4,650; and 894 patients, respectively. The mean age of patients within the CD-S and their comparator cohorts was higher than in the CD-F or CD-FS cohorts (59.9 vs 49.5 vs 49.6 years). At baseline, cardiovascular disease was the most common comorbidity across all condition and comparator cohorts. Condition cohorts had 2-4 times more inpatient visits, 5-8 times more surgical visits, and 2-3 times more endoscopies PPPY than comparator cohorts. Compared with their respective comparator cohort, patients in the 3 condition cohorts had higher medication, medical, and total health care costs. CONCLUSIONS: This study demonstrates a significant economic burden related to fistulas and/or strictures among patients with CD, highlighting the importance of prevention, early recognition, and appropriate management of CD-related complications. DISCLOSURES: Yanni Fan, Ling Zhang, Jennifer S Thompson, and Kimberly G Brodovicz are employees of Boehringer Ingelheim. Rhonda L Bohn, Monik C Jiménez, and Stephani Gray (Bohn Epidemiology, LLC) are paid consultants to Boehringer Ingelheim. Gil Y Melmed reports receiving grants from Pfizer; consulting fees from Boehringer Ingelheim, AbbVie, Arena, BMS, Celgene, Entasis, Ferring Lilly, Fresenius Kabi, Medtronic, Samsung Bioepis, Janssen, Takeda, Pfizer, Prometheus Labs, and TechLab. We conducted a retrospective study using administrative claims data from the Optum Research Database, a database of a commercially insured population in the United States. All patient data were anonymized and deidentified; therefore, informed consent was not necessary. Restrictions apply to the availability of these data because of a contract between Optum and Boehringer Ingelheim, and data are thus unavailable to the public. For enquiries on the dataset analyzed in this study, please contact Optum (https://www.optum.com).

P187 Intestinal ultrasound is accurate for detecting intra-abdominal complications in Crohn’s disease: a meta-analysis

Abstract Background The clinical course of Crohn’s disease (CD) is associated with development of complications including strictures and penetrating lesions such as fistulas and abscesses. Close disease monitoring and optimizing therapy can prevent these complications. Intestinal ultrasound (IUS) is a non-invasive cross-sectional imaging method ideal for frequent assessment of disease activity and intra-abdominal complications. In this meta-analysis we provide an updated assessment of the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, MRI/CT, surgery and pathology. Methods We conducted a literature search in Pubmed/MEDLINE and EMBASE databases from 01-01-1970 up to and including 17-10-2022 for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. A univariate random-effects model was used to calculate the diagnostic test accuracy variables, including the log diagnostic odds ratio and area under the pooled ROC (AUC for SROC). All data were calculated with 95% confidence intervals (CIs). Chi-squared (χ²) test was used to assess study heterogeneity with p < 0.05 indicating significant heterogeneity. Funnel plots were created to assess publication bias. All meta-analysis were performed using the R-package mada. We calculated pooled sensitivity and specificity in Meta-DiSc. Results We identified 1506 studies of which 68 were used for the systematic review. Twenty-three studies with 3863 patients were included in this meta-analysis with an overall moderate to high risk of bias. In total 6 meta-analyses were performed, both for conventional IUS (B-mode) and oral contrast IUS (SICUS) for diagnosing CD-related complications. Pooled overall log diagnostic odds ratio for strictures, fistulas and inflammatory masses by B-mode IUS were 3.56 (2,90-4.21), 3.84 (3.28-4.41) and 3.97 (3.30-4.64) and the AUC were 0.926, 0.896 and 0.960 respectively. Pooled overall diagnostic odds ratio for the diagnosis of strictures, fistulas and inflammatory masses by SICUS were 4.51 (3.28-5.73), 4.80 (3.46-6.14) and 5.46 (3.61-7.30) and the AUC were 0.955, 0.982 and 0.985, respectively. Significant heterogeneity was seen between studies reporting data on diagnosing strictures by B-mode IUS. Conclusion These results indicate that IUS is an accurate tool for the diagnosis of intra-abdominal complications related to CD. IUS as a non-invasive, point-of-care modality is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.

S771 Impact of Early Biologic Therapy in Real-World Cohort of Crohn’s Disease Patients

Introduction: Crohn’s disease (CD) is characterized by transmural inflammation and ongoing inflammatory activity, which over time results in the accumulation of bowel damage, which may lead to complications such as strictures, fistulas/fissures, and abscesses, as well as disability. Optimally controlling inflammation early in the disease course of CD, during the ‘window of opportunity,’ may be the best way to change disease course. Recent evidence and clinical practice guidelines suggest that early biologic therapy is preferred in treating moderate to severe CD. Early use of biologic therapy and achievement of mucosal healing can contribute to disease course modification. We hypothesize that significantly more CD patients treated within 2 years of diagnosis will achieve clinical remission and have less CD-related complications than those treated 2 or more years after diagnosis. Methods: We conducted a retrospective cohort study of CD patients treated within the Military Health System to assess the relationship of timing of initiation of biologic therapy with the control of CD. Data was collected from January 1, 2013 to December 30, 2020 to measure the course of patients’ disease as determined by clinical, biochemical, radiologic, and endoscopic/histologic findings, with an assessment of clinical outcomes and complications to include CD-related emergency room visits, steroid use, hospitalizations, and surgeries. Results: 343 patients with CD were identified, of which 184 were started on biologic therapy within 2 years of diagnosis, while 159 were started on biologic therapy 2 or more years after diagnosis. Patients who initiated biologic therapy within 2 years of diagnosis had significantly fewer CD-related complications (p< 0.0001) (Figure 1a). Evidence of perianal disease at diagnosis was predictive of an increased likelihood of CD-related complications (Figure 1b). Patients on monotherapy with thiopurines prior to biologic therapy were also more likely to experience CD-related complications (Figure 1c). Conclusion: These findings demonstrate that earlier initiation of biologics (within 2 years of diagnosis) results in a lower probability of CD-related complications, including emergency room visits, steroid use, hospitalizations, and surgeries. This real-world study is one of the first to confirm prior clinical trial data on decreased complications in early initiation of biologic therapy in CD patients.Figure 1.: Survival curves for complications with respect to timing of biologic start (1a), presence of perianal disease (1b) and thiopurine therapy prior to biologic stat (1c).

Adalimumab Is Associated With Lower Healthcare Resource and Steroid Use Versus Vedolizumab in Biologic-Naive Crohn's Disease: A Retrospective Claims Database Analysis.

We compared real-world healthcare resource utilization (HRU), Crohn's disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic. Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan-Meier analyses, respectively. Adalimumab- and vedolizumab-treated patients were matched (n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P < 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P < 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline (N ADA = 360, N VDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index (N ADA = 143, N VDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P < 0.001). Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients.

Crohn’s Disease-Related Stoma Complications and Their Impact on Postsurgical Course

Introduction: Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. The diversion through a colostomy or an ileostomy is sometimes required for disease control. In these patients, common stoma-related complications sum up with CD-related complications and often require revisional surgery. Methods: The aim of the study was to assess stoma morbidity after surgery for CD and to identify the burden of CD-related or CD-associated complications. Thus, details of past medical history, surgery, and follow-up of 54 consecutive patients operated on for CD with any sort of stoma were retrieved from the stoma therapist prospectively maintained database. Results: In our series, 23 patients had a colostomy, and 31 patients had an ileostomy. Complications occurred after stoma creation in 38 patients (70%) at a median of 1.3 months (interquartile range 0.6–7.2). CD-related complications arose in 8 patients (including pyoderma gangrenosum in 3 patients, peristomal fistulae in 2, granulomas in 2, and peristomal abscess in 1). Patients with CD-related complications tended to have a shorter disease duration (p = 0.07) and higher occurrence of CD-related complications was associated with end-stoma (p = 0.006). In this cohort, 11 cases had to be surgically treated for peristomal fistulae or abscess, parastomal hernia, prolapse, pyoderma gangrenosum, and recurrent CD. Discussion/Conclusions: In patients with CD, stoma creation is burdened by a high rate of postoperative complication and a relevant rate is specifically related to CD. Often these patients are required to be reoperated on to redo the stoma. Moreover, end-stoma configuration and aggressive CD phenotype are associated to a higher rate of complications.

P508 The impact of disease duration and early biologic treatment on transmural healing in Crohn’s disease

Abstract Background Although transmural healing (TH) has not yet been considered a formal target in CD, it is considered a desired goal, as it seems to be associated with better outcomes. Early biologic treatment has been shown to lead to higher clinical remission and increased endoscopic healing. However, to date, there is no information on the impact of disease duration on TH. We aimed to assess the efficacy of early biologic treatment on the achievement of TH. Methods Unicentre retrospective cohort study comparing patients who started early and late biologic therapy (defined as ≤ 12 months vs &amp;gt; 12 months from diagnosis). We included patients with CD who were receiving biologic therapy, and had a baseline computed tomography enterography (CTE) or magnetic resonance enterography (MRE) before the initiation of a biologic (median 2.5, IQR 0–50 months), and a follow-up CTE/MRE performed 12 ± 6 months after therapy initiation. Endoscopic healing was defined as a SES-CD score &amp;lt;3. Three experienced radiologists blinded to the therapeutic group reviewed every CTE and MRE and assessed several pre-defined parameters of cross-sectional inflammation. TH was defined as the absence of active inflammation, extra-enteric signs, and CD-related complications (strictures, fistulas or abscesses). The effect of early biologic treatment on transmural healing was analysed using logistic regression. Results 60 patients were included (51.7% males), with a median age at diagnosis of 24.5 years old (IQR 17.5–32.5). Most patients had ileocolonic disease (58.3%) and non-stricturing non-penetrating phenotype (60%). Twenty-eight patients (46.7%) started biologic therapy within the first 12 months of diagnosis. There were no significant differences in baseline clinical features or baseline radiologic assessment between the groups, except for the extension of the most affected segment, which was higher in the group of late biologic therapy (197 vs 129.5mm, p=0.05) (Table 1). Patients on early biologic treatment achieved endoscopic healing more frequently than those on late biologic treatment (65.4% vs 23.3%, p=0.002). Early biologic treatment was also associated with increased transmural healing (OR 4.1, 95% CI 1.2–13.6, p=0.02). In a multivariate model including baseline characteristics of the disease, only the use of biologics within the first 12 months and the absence of ileocolonic disease were significant predictors of the achievement of transmural healing (Figure 1). Conclusion Early biologic treatment seems to be independently associated with higher transmural healing rates, further adding to the relevance of early intervention in CD. Our findings are limited by the small sample size and short follow-up.

P315 High symptom burden and impact on health-related quality of life in patients with Crohn’s perianal fistulas: results from a global burden of illness study

Abstract Background Perianal fistulas (PAF) are a common complication in Crohn’s disease (CD) and can be associated with an increased burden of illness. A global study was conducted to assess the burden of illness in patients with Crohn’s perianal fistulas (CPF) compared with patients with CD without PAF (non-PAF CD). Here we present patient symptom burden and impact on HRQoL. Methods This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as having non-PAF CD (cohort, 1) or CPF without PAF-related surgery (cohort, 2) or CPF with PAF-related surgery (cohort, 3). Customised questions and validated general and disease-specific patient-reported outcome data were collected via a, 45-min IRB/EC-approved web-enabled questionnaire. Symptom burden and impact on HRQoL were evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ, scores, 1–7 [low–optimum] with, 2-week recall period) in all cohorts and Quality of Life in Patients with Anal Fistula (QoLAF, scores, 14–70 [low–high impact]) in cohorts, 2 and, 3. Data were analysed using descriptive statistics. Results Of, 929 patients recruited (cohort, 1, n=620; cohort, 2, n=174; cohort, 3, n=135), 58–69% were male and, 55–67% were aged, 21–40 years across all cohorts. Cohorts, 2 and, 3 experienced a significantly higher frequency of CD-related complications than cohort, 1 (mean [standard deviation, SD]:, 9.4 [4.5] and, 11.1 [5.2] vs, 6.0 [4.1], respectively; both p &amp;lt;0.05, Table, 1) and had a higher number of CD-related surgeries (other than PAF-related surgeries) in the past, 12 months (mean [SD]:, 1.8 [1.1], p =0.109 and, 2.2 [1.3], p &amp;lt;0.0001 vs, 1.5 [0.9], respectively). In patients with CPF, a smaller proportion in cohort, 2 had active PAF vs cohort, 3 (136 [78%] vs, 119 [88%], respectively; p =0.022) and a smaller proportion had experience with post-treatment PAF recurrence/persistence in cohort, 2 vs cohort, 3 (84 [48%] vs, 80 [59%], respectively; p =0.055). Overall SIBDQ scores were significantly lower (worse) in cohorts, 2 and, 3 than in cohort, 1 (3.8 and, 3.7 vs, 4.1 respectively; both p &amp;lt;0.001). In patients with CPF, total QoLAF scores were comparable between cohorts, 2 and, 3 (41 and, 42, respectively), although patients in cohort, 3 had a significantly higher (worse) score in the physical impact domain compared with cohort, 2 (21 vs, 19, respectively; p &amp;lt;0.05). Conclusion In this large global study, we observed that patients with CPF had incrementally higher symptom burden, owing to both CD and PAF, compared with patients with non-PAF CD. For patients with CPF, there was no difference in HRQoL irrespective of whether they had received PAF-related surgery or not.

Clinical Value of Tissue Transglutaminase Antibodies in Celiac Patients over a Long Term Follow-Up.

Introduction & Aim: Anti-tissue transglutaminase antibody (tTGA) titer is used during the follow-up of celiac patients to evaluate gluten-free diet (GFD) responsiveness. However, no clear data are available on this issue. The aim of this study was to evaluate tTGA significance during celiac disease (CD) monitoring. Methods: From January 2017 to January 2020, consecutive CD patients on a GFD with persistent positive tTGA were enrolled. Antibody titres were evaluated on a yearly basis from CD diagnosis to the last follow-up. Urinary gluten detection tests, duodenal histology and capsule enteroscopy (CE) were performed. A tTGA-positive cohort was compared with a control group composed of 212 treated CD patients with negative tTGA. Results: 65 patients (12% males, median age at enrollment and CD diagnosis, 37 (14–86) and 31 (1–76), respectively, median follow up 4 (1–26) years) presented with positive tTGA during follow-up. Overall, the tTGA titres were 3 (1–79) fold increased (ULN). Three different tTGA trends were recognized: (I) 36 (55%) patients with a progressive titres decrease; (II) 16 (25%) patients with a fluctuating behavior; (III) 13 (20%) patients with a steady state or increased titres. tTGA+ patients did not present with different clinical and demographic parameters. Duodenal atrophy was present in 10% vs. 36% of the tTGA positive vs. negative group (p < 0.005), respectively. Gluten detection results were positive in 3 (8%) cases, all in the III group. In tTGA+ patients, CE did not identify any CD-related complications. Conclusions: tTGA positivity during CD follow up did not present a relevant clinical significance without association with autoimmune comorbidities and mucosal damage.

Adherence to gluten-free diet and follow-up of pediatric celiac disease patients, during childhood and after transition to adult care.

Long-term data on pediatric celiac disease (CD) patients after transition to adult care is scarce. We aimed to evaluate patients' adherence to a gluten-free diet (GFD), the normalization of celiac serology and the frequency of follow-up before age 18, and to study changes in adherence and follow-up frequency after transition to adult care. Presenting symptoms, serology and biopsy results, patients' reported GFD adherence, frequency of follow-up visits, and complications before and after 18 years were collected for CD patients diagnosed between 1998 and 2017. Of 441 CD patients diagnosed and followed in childhood, a quarter (108/441) were over 18 y (years) at data collection. Median age at diagnosis 7.1 y (9 months-18 y), at data collection 23 y (18-38 y), disease duration 11.3 y (2-36 y). Below the age of 18 y, most patients 386/436 (88.5%) reported adherence to GFD, and most 372/425 (85.7%) normalized serology. Of the 441patients, only 3 failed to attend any follow-up visit, and 338/441 (76.6%) attended yearly visits. Over the age 18 y, serology testing was done in 78/108 (72.2%), every 1-3 y in 46/78 (59%). Serology normalized in 61/78 (78.2%). Most adult patients 77/108 (71.5%) never attended a gastroenterology clinic. CD-related complications were rare. Younger age at diagnosis, regular follow-up visits in childhood, resolution of symptoms, and normalization of serology before age 18 were identified as predictors of negative serology after the age of 18 y.Conclusions: Children who have regular follow-up and normalize serology before age 18 years are likely to maintain a GFD and have negative serology as adults. What is Known: • The rate of adherence to gluten-free diet (GFD) is higher among children compared to adults. • Data on long-term follow-up after transition to adult care is scarce. What is New: • Patients diagnosed with CD at a younger age (<12 y), who have yearly follow-up visits, resolution of symptoms, and negative serology in childhood are very likely to maintain GFD and have negative serology as adults. • Even though most patients do not attend GI clinics after transition to adulthood, most adhere to GFD, and complications are rare.

Early Combined Immunosuppression Reduces Complications in Long-standing Crohn's Disease: A Post Hoc Analysis of REACT

Crohn's disease (CD) can lead to bowel damage, stricturing, and obstruction thereby resulting in surgery and hospitalization. The Randomized Evaluation of an Algorithm for Crohn's Treatment (REACT) trial showed that early combined immunosuppression (ECI) with symptom-based treatment escalation for 24 months resulted in a lower risk of surgery, hospitalization, or CD-related complications compared with conventional management (CM).1 Treatment earlier in the disease course may be associated with reduced risk of complications compared with later initiation, although data are sparse.2 We performed a post hoc analysis of REACT to evaluate the impact of baseline disease duration on surgery, hospitalization, or CD-related complications in patients treated with ECI compared with CM.

Early Combined Immunosuppression May Be More Effective for Reducing Complications in Isolated Colonic- vs Ileal-Dominant Crohn Disease.

We assessed whether differential efficacy of early combined immunosuppression (ECI) in comparison with conventional management (CM) is present in patients with Crohn disease (CD) according to disease location. In this posthoc analysis of the Randomized Evaluation of an Algorithm for Crohn's Treatment trial, the effect of ECI vs CM modified by disease location (isolated-colonic vs ileal-dominant) in terms of time to first complication (hospitalization, surgery, or disease-related complications-presence of a new abscess, fistula, or stricture; serious worsening of disease activity; extraintestinal manifestations) was analyzed using a marginal Cox proportional hazard model to account for cluster randomization. Factors adjusted included practice size, country, and other covariates selected in a backward logistic regression analysis with the first composition as outcome and P < 0.10. Of the 1969 patients with CD, 435 had isolated colonic CD (ECI n = 257, CM n = 178) and 1534 had ileal CD (ECI n = 817, CM n = 717). Over 24 months there was a significant differential impact for ECI vs CM for reducing the risk of a CD-related complication between patients with colonic CD and ileal CD (colonic CD hazard ratio [HR] = 0.51; 95% CI, 0.30-0.85 vs ileal CD HR = 0.79; 95% CI, 0.57-1.10; P = 0.033). No difference was identified between ECI vs CM for reducing the risk of surgery (colonic HR = 0.52 vs ileal HR = 0.74; P = 0.468) or hospitalization (colonic HR = 0.77 vs ileal HR = 0.83; P = 0.806). In this posthoc analysis of the Randomized Evaluation of an Algorithm for Crohn's Treatment trial, symptom-based ECI was associated with greater efficacy for reducing the risk of CD-related complications in patients with colonic disease location relative to ileal disease location.

Postoperative Endoscopic Recurrence on the Neoterminal Ileum But Not on the Anastomosis Is Mainly Driving Long-Term Outcomes in Crohn's Disease.

Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.

Comparison of small intestinal contrast ultrasound with magnetic resonance enterography in pediatric Crohn's disease.

AimTo compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients investigated for Crohn's disease (CD) attending a UK tertiary center.Methods and ResultsPatients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD‐related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2–17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68).ConclusionsSICUS offers a radiation‐free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice.

P101 Incidence of peri-pregnancy flares among patients with Crohn's disease

BACKGROUND: Evidence informing providers and payers regarding the appropriate management of women with reproductive potential continues to grow and was primarily stimulated by the FDA's Pregnancy and Lactation Labeling Rule. The objective of this analysis was to examine the unmet clinical needs of patients with Crohn's disease (CD) during pregnancy. METHODS: CD patients with pregnancies resulting in live births were identified in the MarketScan® database (1/2010-9/2016) using ICD-CM/CPT/MS-DRG codes. The estimated conception date (index date) was calculated based on the gestational age indicated by the diagnosis or procedure code for delivery. Continuous enrollment from the baseline (BL) period (6-months pre-index) through the postpartum period (6-months post-delivery) was required. Clinical proxies were developed to assess flares during the study period: (1) At least 2 ICD-CM codes for CD-related symptoms: abdominal pain, blood in stool, diarrhea, fatigue, fever, loss of appetite, weight loss, rashes; (2) ICD-CM code for CD-related complication: abscess, anal fissure, arthritis, bowel obstruction/stricture, fissure, fistula, gallstone, inflammation of the eye/mouth, kidney stone, liver disease, ulcers; (3) CD-related hospitalization/ER visit; (4) 60% increase in CD-related outpatient visits from BL; (5) addition or potency increase of oral corticosteroid from BL; (6) addition or dose increase in biologic therapy from BL; and (7) addition of other CD indicated therapies from BL. An assumption was made that only a single flare could occur within 30 days. RESULTS: 1,726 successful pregnancies among CD patients were identified. The mean age was 30.3 years, mean (SD) Deyo-Charlson comorbidity index was 0.1 (0.4), most patients had commercial PPO coverage (63.4%), and the most prevalent comorbid condition was infection (42.5%). There were no significant differences in BL characteristics between pregnancies with and without flares. Among the 1,726 pregnancies, there were a total of 5,074 flares (1,268 flares [25.0%] during the BL period, 2,227 flares [43.9%] during the pregnancy period, and 1,579 flares [31.1%] during the post-partum period). To account for differences in the duration of each peri-pregnancy period (baseline [6.0 months], pregnancy [9.2 months], postpartum [6 months]), average monthly flare rates were calculated. The rates were 211.3, 241.7, and 263.2 flares/month, respectively, for the BL, pregnancy and post-partum periods. The most frequent clinical proxies for flares during the BL period were an increase in CD-related outpatient visits from BL (23.7%) and CD-related symptoms (23.0%). The most frequent clinical proxies for flares during both the pregnancy and postpartum periods were the addition or increase in dose of CD-indicated therapies (45.6% pregnancy period, 35.8% postpartum period) and CD-related complications (25.0% pregnancy period, 35.4% postpartum period). CONCLUSION(S): The consistently high risk of flares during the peri-pregnancy period demonstrates the need for optimizing the management of CD. While sole reliance on claims data is a limitation in assessing poor CD control, the use of clinical proxies to explore national trends in CD disease control might help uncover unmet needs. Healthcare professionals should aim for disease control prior to pregnancy and have a treatment plan during and after pregnancy to optimize clinical outcomes and minimize CD-related complications for women.

Significant Medical and Surgical Morbidity in Perianal Crohn's Disease: Results from a Territory-Wide Study.

The presence of perianal fistulas in Crohn's disease [CD] denotes increased disease aggressiveness. We studied the epidemiology and clinical outcomes of perianal CD [PCD] using the Hong Kong territory-wide IBD Registry [HKIBDR]. Consecutive patients with PCD were identified from the HKIBDR, and disease characteristics, treatments, and outcomes were analysed. The risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. Among 981 patients with CD with 10530 patient-years of follow-up, 283 [28.8%] had perianal involvement, of which 120 [42.4%] were as first presentation. The mean age at diagnosis of PCD was 29.1 years, and 78.8% were male. The median follow-up duration was 106 months (interquartile range [IQR]: 65-161 months]. Perianal fistula [84.8%] and perianal abscess [52.7%] were the two commonest forms. Male, younger age at diagnosis of CD, and penetrating phenotypes were associated with development of PCD in multivariate analysis. Of 242 patients with fistulizing PCD, 70 [29.2%] required ≥5 courses of antibiotics, and 98 [40.5%] had ≥2 surgical procedures. Nine patients required defunctioning surgery and 4 required proctectomy. Eighty-four patients [34.7%] received biologics. Cumulative probabilities for use of biologics were 4.7%, 5.8%, and 8.6% at 12 months, 36 months, and 96 months, respectively, while the probabilities for surgery were 67.2%, 71.6%, and 77.7%, respectively. Five mortalities were recorded, including 2 cases of anal cancer, 2 CD-related complications, and one case of pneumonia. Over 40% of CD patients presented with perianal disease at diagnosis. Patients with PCD had poor outcome, with young age of onset, multiple antibiotic use, and repeated surgery.

A Single Nucleotide Polymorphism in the Vitamin D Receptor Gene Is Associated With Decreased Levels of the Protein and a Penetrating Pattern in Crohn's Disease.

Vitamin D signaling modulates inflammation through the vitamin D receptor (VDR). The synonymous single nucleotide polymorphism (SNP) rs731236, located in the VDR gene, has been associated with a higher risk of Crohn's disease (CD). We analyzed differences in VDR expression levels among CD patients who were homozygous for allelic variants in this SNP and their relevance for disease course. DNA was extracted from blood samples of CD patients, and SNP genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Fresh blood from patients was used to isolate peripheral blood mononuclear cells (PBMCs) or to determine the expression of adhesion molecules by flow cytometry. We analyzed the gene expression of VDR and several cytokines in PBMCs using real-time polymerase chain reaction and the protein levels of VDR, NFκB, and IκBα by immunoblot. In addition, we collected complete clinical data for a group of 103 patients, including age at diagnosis, disease location, and disease behavior to compare patient characteristics with respect to genotype. We found that CD patients who were homozygous for the risk allele presented lower levels of VDR protein in PBMCs, and that this was associated with an upregulation of IL1β mRNA and activation of lymphocytic adhesion molecules. These patients had a higher risk of developing a B3-penetrating phenotype and of needing to undergo surgery. Our data highlight the relevance of vitamin D/VDR signaling in modulating the subjacent inflammation that leads to CD-related complications.

Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease.

Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease.