Crohn's Disease Patients In Clinical Remission Research Articles

P676 Intestinal ultrasound accurately predicts therapy failure in Crohn's disease patients during a biologics-induced remission

Abstract Background Intestinal Ultrasound (IUS) is a non-invasive modality that can assess disease activity, complications, and treatment follow-up in Crohn's disease (CD) patients. IUS is reliable, patient-friendly, and allows frequent monitoring of disease activity. While 3mm bowel wall thickness (BWT) was repeatedly found to correlate with intestinal inflammation, whether this threshold also best predicts clinically relevant future outcomes is still largely unknown. We aim to investigate the role of IUS to predict the risk of therapy failure in biologics-treated CD patients in clinical remission. Methods Our analysis included a retrospective cohort of CD patients in clinical remission (HBI≤4) induces by biologic drugs, who underwent IUS 12 (±2) months after induction. We examined the correlation of IUS activity parameters with future therapy failure (defined as drug discontinuation, dose escalation, new corticosteroid use, CD-related hospitalization, or surgery). Results A total of 57 patients (58% male), with ileal (65%) or ileocolonic (35%) CD, on biological therapy (28% infliximab, 51% adalimumab, 10.5% vedolizumab, 10.5% ustekinumab) were included. Therapy failure occurred in 54.3% (32.2% drug discontinuation, 45.2% dose escalation, 16.2% corticosteroid use and 6.4% hospitalization) during a median follow-up of 12 (IQR 5-22) months after IUS. Of all IUS parameters examined, therapy failure was associated only with increased BWT; BWT > 5mm (hazard ratio (HR) 2.3 [confidence interval (CI) 1.03-5.3], p= 0.041). Interestingly, there was risk plateauing with increased BWT above this cutoff (>5.5 mm (HR 2.2 [CI 1-5.10], p=0.048); >6mm (HR 2.6 [CI 1.17-6.12], p=0.019); >6.5 mm (HR 2.5 [CI 1.08-5.83], p=0.032)) (Figure 1). A BWT cutoff of 3mm could not discriminate patients with future treatment failure. Conclusion Our findings suggest that BWT of > 5 mm during clinical remission can predict subsequent treatment failure in CD patients treated with biologics. Our results support the use of IUS in monitoring CD during remission, and may point to a novel threshold predicting disease reactivation.

Usefulness of the capsule endoscopy Crohn's disease activity index in assessing the necessity of early additional treatment in patients with Crohn's disease in clinical remission.

The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) was recently reported as a new scoring system to evaluate the mucosal lesions of patients with Crohn's disease (CD). We investigated whether CECDAI is useful for assessing the necessity of early additional treatment in patients with CD in clinical remission.Twenty-one patients with small intestinal CD in clinical remission underwent capsule endoscopy (CE). The CECDAI and Lewis score (LS) were used to evaluate the intestinal lesions. We analyzed the correlations between several biomarkers and CECDAI or LS and examined the changes in therapeutic regimens based on the CECDAI.CE identified intestinal abnormalities in most CD patients in clinical remission: 81.0% and 85.7%, as assessed using CECDAI and LS, respectively. A significant positive correlation was observed between the CDAI and LS (P = .025), as well as between CDAI and CECDAI (P = .014) in these cases. Compared to LS, CECDAI scores were more evenly distributed. No significant correlations were observed between endoscopic scores and serum markers, including CRP, hemoglobin, and albumin levels. Additional treatment was performed significantly more often in patients with moderate-severe disease activity (CECDAI ≥5.8) (P = .012) than in those with normal (CECDAI <3.5) and mild (3.5≤CECDAI<5.8) disease activity. Resection of the small intestine did not affect the small bowel transit time or CE score.CECDAI is useful in evaluating mucosal lesions in small bowel CD patients in clinical remission and helps in assessing the requirement for additional treatment for these patients, including those who undergo intestinal resection.

Changes in the Crohn's Disease Activity Index and Safety of Administering Saccharomyces Boulardii in Patients with Crohn's Disease in Clinical Remission: A Single Hospital-based Retrospective Cohort Study.

Crohn's disease (CD) is characterized by uncontrolled inflammation of the intestine. Saccharomyces boulardii (S. boulardii), a probiotic, stabilizes the intestinal wall. This study examined the changes in the CD activity index (CDAI) after taking S. boulardii in patients with CD in clinical remission. In this single hospital-based retrospective cohort study, the medical records of CD patients in clinical remission, who had received S. boulardii for more than 6 months, were reviewed. The CDAI, BMI, and serum levels of hemoglobin (Hb), ferritin, iron, vitamin B12, folate, total protein, albumin, total cholesterol, CRP, and fecal calprotectin (FC) between the initiation and the 6th month were compared. The timing and reasons for the discontinuation were also investigated. One hundred and fifty-four patients were included, and 92 patients, who received for more than 6 months, were analyzed. The changes in CDAI, BMI, Hb, and total cholesterol were significant as follows: CDAI from 38.52 to 30.53 (p<0.01), BMI (kg/m2 ) from 23.38 to 23.97 (p<0.01), Hb (g/dL) from 13.73 to 14.03 (p<0.01), and total cholesterol (mg/dL) from 154.9 to 161.5 (p<0.01). On the other hand, the changes in FC, CRP, ferritin, vitamin B12, folate, total protein, and albumin were not statistically significant. Only one patient stopped due to a flare-up, but this was not believed to be related to the drug. In patients with CD in remission, S. boulardii appears to improve the CDAI, BMI, serum Hb, and total cholesterol level without safety issues. Further randomized controlled studies will be needed.

Significance of endoscopic deep small bowel evaluation using balloon-assisted enteroscopy for Crohn’s disease in clinical remission

Small bowel lesions of Crohn's disease (CD) are known to be associated with a poor prognosis; however, endoscopic healing leads to favorable patients' outcome. The aim of this study was to clarify the clinical impact of assessing deep small bowel lesions (DSB) using balloon-assisted enteroscopy (BAE) on CD patients in clinical remission. From January 2012 to July 2018, a total of 100 CD patients in clinical remission were enrolled to undergo trans-anal enteroscopy using single-balloon enteroscope. Endoscopic evaluations at the terminal ileum (TI) were performed using a partial Simple Endoscopic Score for CD (pSES-CD). Endoscopic evaluations at the DSB used a modified partial SES-CD (mpSES-CD). We evaluated the factors associated with relapse, and the correlation of endoscopic score between the TI and DSB. For this study, relapse was defined as hospitalization within a year from enteroscopy. 30 patients (30.0%) relapsed within a year from enteroscopy. Multivariate logistic regression analysis revealed that the Harvey-Bradshaw Index (OR 1.77, 95% CI 1.18-2.65; p = 0.003) and an mpSES-CD at DSB (OR 3.10, 95% CI 1.86-5.15; p = 0.001) were independent predictors for relapse, whereas a SES-CD at the TI did not exhibit independence. There was a significant correlation trend between the relapse rate and greater than 5 points of an mpSES-CD at DSB; however, there was no correlation between the relapse rate and pSES-CD at the TI. Even when Crohn's disease is in remission, it is important to evaluate DSB using BAE to assess endoscopic mucosal healing.

Risk Factors for Rescue Therapy in Crohn's Patients Maintained on Infliximab After Withdrawal of the Immunomodulator: A Long-Term Follow-Up.

Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn's disease (CD) patients and theoptimal length of dual therapy are still debated. To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6months (range 5.4-129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0months (range 4-74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis <16years versus >40years (HR 4.55, 95% CI 1.18-17.62, p=0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p=0.028), and duration of combination therapy <6months (HR 5.68, 95% CI 1.58, 20.36, p=0.007) increased risk forrescue therapy. A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse

Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI]<150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Analysis of SHIP1 expression and activity in Crohn's disease patients.

BackgroundSH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn’s disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients.MethodsSHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880.ResultsSHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort.ConclusionsAberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.

Impact of Smoking Cessation on the Clinical Course of Crohn's Disease Under Current Therapeutic Algorithms: A Multicenter Prospective Study.

Given the importance of tobacco smoking (TS) as the only environmental factor repeatedly linked to the development of the Crohn's disease (CD), it is surprising that very few prospective studies have assessed whether TS is associated with an increased frequency of clinical relapse. Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants. This was a multicenter prospective cohort study, which included 573 CD patients in clinical remission with various smoking habits. All smokers were advised to quit. Patients not exposed to tobacco before inclusion (non- and former smokers), continuing smokers, and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years. A total of 148 continuing smokers, 190 nonsmokers, 160 former smokers, and 75 quitters were included. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval (CI): 1.10-2.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers. Smoking was an independent predictor for disease relapse in the multivariate analysis (hazard ratio: 1.58 (95% CI 1.20-2.09). In the time-dependent analysis, continuing smokers had earlier relapse, regardless of anti-TNF or immunosuppressant use. Continuing smokers have more disease relapses, and patients who quit smoking have a similar relapse incidence compared with nonsmokers.

Normalización a largo plazo de la calidad de vida de los pacientes con enfermedad de Crohn con terapia de mantenimiento con adalimumab

BackgroundMaintenance treatment of Crohn's disease (CD) with adalimumab achieves sustained clinical remission and improves health-related quality of life (HRQOL) of patients. There is, however, no information about its long-term effect on normalization of patient's perceived health. ObjectivesTo determine the long-term normal perception of health in CD patients in clinical remission with adalimumab. MethodsRetrospective, observational study in CD patients in clinical remission for 36 months follow-up, treated with adalimumab 40mg eow. Patients requiring a change of treatment or surgery were not included. HRQOL was assessed with the specific questionnaire IBDQ-36. The normalization of health was defined as an overall score ≥ 209. ResultsTwenty eight patients were included in sustained clinical remission for 36 months. Three patients required further escalation and de-escalation of the dose. The IBDQ-36 overall score remained unchanged in patients with inactive stable CD and even tended to increase with time (median overall score of 230 at 6 months and 238 at 3 years). The rate of normalization of health increased with time (68% to 78% at 6 and 36 months respectively). ConclusionsSustained clinical remission with effective maintenance treatment with adalimumab restores the perception of normal health of most of the patients with CD.

Peripheral Monocyte Functions and Activation in Patients with Quiescent Crohn’s Disease

Recent developments suggest a causal link between inflammation and impaired bacterial clearance in Crohn’s disease (CD) due to alterations of intestinal macrophages. Studies suggest that excessive inflammation is the consequence of an underlying immunodeficiency rather than the primary cause of CD pathogenesis. We characterized phenotypic and functional features of peripheral blood monocytes of patients with quiescent CD (n = 18) and healthy controls (n = 19) by analyses of cell surface molecule expression, cell adherence, migration, chemotaxis, phagocytosis, oxidative burst, and cytokine expression and secretion with or without lipopolysaccharide (LPS) priming. Peripheral blood monocytes of patients with inactive CD showed normal expression of cell surface molecules (CD14, CD16, CD116), adherence to plastic surfaces, spontaneous migration, chemotaxis towards LTB4, phagocytosis of E. coli, and production of reactive oxygen species. Interestingly, peripheral blood monocytes of CD patients secreted higher levels of IL1β (p<.05). Upon LPS priming we found a decreased release of IL10 (p<.05) and higher levels of CCL2 (p<.001) and CCL5 (p<.05). The expression and release of TNFα, IFNγ, IL4, IL6, IL8, IL13, IL17, CXCL9, and CXCL10 were not altered compared to healthy controls. Based on our phenotypic and functional studies, peripheral blood monocytes from CD patients in clinical remission were not impaired compared to healthy controls. Our results highlight that defective innate immune mechanisms in CD seems to play a role in the (inflamed) intestinal mucosa rather than in peripheral blood.

Hand-held fractional exhaled nitric oxide measurements as a non-invasive indicator of systemic inflammation in Crohn's disease

Background and aimsActive inflammatory bowel disease (IBD) is associated with increased activity of inducible nitric oxide synthase (iNOS), which increases both mucosal and plasma nitric oxide (NO) levels. Increased fractional exhaled nitric oxide (FeNO) levels have been described in patients with IBD. Currently, hand-held FeNO measurement devices are available, enabling a fast in-office analysis of this non-invasive disease activity marker. In this pilot study, we investigated the utility of in-office FENO measurements in patients with Crohn's disease (CD). MethodsFifty CD patients and 25 healthy controls (HC) were included, all of whom were free of atopic or pulmonary disorders and respiratory symptoms at the time of inclusion. The Crohn's disease activity index (CDAI) was calculated, and the inflammatory parameters and fecal calprotectin levels were assessed. FeNO was measured with a hand-held device. ResultsA significant increase in FeNO (median, [interquartile range]) was observed in steroid-free CD patients with clinically active disease (CDAI>150; 22 [8] ppb) compared with CD patients in clinical remission (CDAI<150; 11 [6] ppb; P<0.001) and HC's (17 [9] ppb; P<0.05). Active CD patients treated with corticosteroids had significantly lower FeNO compared with active CD patients without steroids (12 [10] ppb vs 25 [19] ppb; P<0.05). FeNO displayed a strong correlation with the CDAI (R=0.68; P<0.001). Fair correlations were found between FeNO and several systemic inflammatory markers, but no significant correlation was found with fecal calprotectin. ConclusionThis pilot study suggests that hand-held FeNO measurements could be an attractive non-invasive indicator of systemic inflammation in Crohn's disease.

PTU-106 A prospective single centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease patients

IntroductionFaecal calprotectin (FC) has become an established non-invasive, sensitive marker of intestinal inflammation in Crohn's disease (CD). A single measurement of FC is used in clinical practice to aid decision...

Muscle Performance in Patients With Crohnʼs Disease in Clinical Remission

Because patients with Crohn's disease (CD) often show increased energy expenditure, nutritional deficiencies, and general fatigue, all which may persist after a flare, we hypothesized that CD could alter muscle mass and function. This study aimed to assess muscle strength and endurance in CD patients in clinical remission and the influencing factors. Forty-one outpatients (17 men and 24 women; age, 37 +/- 10 yr), in remission (CD Activity Index < 150) for > 3 months, and 25 age-matched healthy controls (10 men and 15 women; age, 37 +/- 13 yr) were evaluated. Evaluation included a sit-up test, hand-grip strength test, hand-grip endurance test, lower limb strength test, and lower limb endurance test (LE), as well as a measure of physical activity. No significant difference was found between CD and control groups regarding weight, height, body mass index, fat mass, and fat-free mass. Strength performance was lower in CD subjects compared with controls, particularly for lower limb indexes: lower limb strength test (-24.6%, P < 0.001), LE (-25.8%, P < 0.001), and sit-up test (-25.1%, P < 0.001). Previous disease severity, disease duration, the cumulative dose of glucocorticosteroids, current inflammation, and global habitual physical activity did not affect muscle performance. A recent use of steroids improved LE. CD patients in clinical remission have decreased muscle function that may affect their quality of life. This pattern is reflected by reduced strength and endurance indexes, particularly for lower limbs. The reasons for these changes need further study. Strength training should be assessed in these patients.