Crohn's Disease Activity Index Research Articles

DOP86 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD).

Abstract Background CT-P13 subcutaneous (SC) infliximab formulation showed comparable efficacy and safety with CT-P13 intravenous (IV) infliximab in inflammatory bowel disease (IBD)1 and rheumatoid arthritis2. This study aimed to demonstrate the superiority of CT-P13 SC over placebo as maintenance therapy after induction therapy of CT-P13 IV in patient with Crohn’s disease (CD). Methods Moderately to severely active CD patients with Crohn’s disease activity index (CDAI) score 220 to 450 and simplified endoscopic activity score for Crohn’s disease (SES-CD) of ≥6 points for ileal-colonic CD or ≥4 points including ulcer score from at least 1 segment for ileal CD or colonic CD were enrolled LIBERTY-CD study (NCT03945019) and treated with open-label CT-P13 IV 5 mg/kg at Weeks 0, 2 and 6 as induction therapy. At Week 10, patients who had a clinical response were randomised (2:1) to receive either CT-P13 SC 120 mg (CT-P13 SC) or placebo every 2 weeks up to Week 54. At Week 54, clinical remission and endoscopic response were assessed as co-primary endpoints. Clinical response, clinical remission (alternative definition), endoscopic remission, and corticosteroid-free remission were assessed at Week 54 as key secondary endpoint. Safety was evaluated up to Week 54. Results A total of 396 patients were enrolled and 343 patients (86.6%) were randomised (231 in CT-P13 SC arm and 112 in placebo arm) at Week 10. At Week 54, the clinical remission rate was greater in CT-P13 SC arm than placebo arm (62.3% and 32.1% respectively, with P <0.0001). The endoscopic response rate was also greater in CT-P13 arm than placebo arm (51.1% and 17.9% respectively, with P <0.0001). CT-P13 SC also had significantly greater efficacy on key secondary endpoints results compared to placebo arm (Table 1). Safety profiles were generally comparable between CT-P13 SC and placebo arms, but a single death was reported during the maintenance phase (Table 2). Conclusion CT-P13 SC was more effective than placebo in clinical remission, endoscopic response, clinical response, clinical remission (alternative definition), endoscopic remission, and corticosteroid-free remission at Week 54. No new safety concerns were found during treatment of CT-P13 SC. These results demonstrate that maintenance therapy with CT-P13 SC provides both a robust clinical benefit and the convenience of SC administration to moderately to severely active CD patients. [1] Schreiber et al., 2021. Gastroenterology 2021;160:2340–23 [2] Westhovens et al., 2020. Rheumatology 2020;00:1

P105 Epithelial microRNA signatures as potential biomarkers in Crohn’s disease related to clinical and endoscopic activity

Abstract Background Emerging evidence suggests that epithelial cell-derived microRNAs (miRNA) are involved in the pathogenesis of inflammatory bowel disease; however, as of now specific implications in the real clinical practice, especially in relation to biologics use are yet far-fetched. Therefore, we tried to investigate specific epithelial cell derived miRNA signatures related to clinical and endoscopic activity in Crohn’s disease (CD) patients. Methods We prospectively collected terminal ileum tissue samples via ileocolonoscopy from healthy control (n=12), CD patients in remission (n=32) and active CD patients (n=36). CD remission was defined as clinical remission of Crohn's disease activity index (CDAI) <150 and achievement of endoscopic mucosal healing. Both inflamed and non-inflamed lesions were sampled in the active CD patients. Clinical information, medication use, chemistry data were measured within a week from the tissue sample date. miRNA levels were measured by small-RNA sequencing and qRT-PCR. Diagnostic ability of specific miRNA found were evaluated by receiver operating characteristic (ROC) curve analysis. Results The study cohort was followed up until January 2022. Mean follow-up period of the prospective CD cohort was 13.06 months. In comparing to the healthy control, CD patients in remission and active state revealed specific miRNA profiles in small-RNA sequencing. Through RT-PCR validation, we found that the expression levels of miR-141-3p, miR-338-3p, miR-378a-3p, and miR-200b-3p were significantly decreased, while miR-125b-5p, miR-29b-3p and miR-155-5p were significantly increased in the inflamed tissue of active CD patients. Moreover, in case of active CD patients, expressions of miR-150-5p, miR-200b-3p and miR-155-5p were significantly down-regulated in those using biologics, compared with biologics naïve patients. This may suggest that these miRNAs were not only as biomarkers of CD patients, but also as biomarkers related to inflammation and biologics response. ROC curve analysis suggested miRNAs with different diagnostic activity related to both clinical disease activity and endoscopic inflammation status. MiR-338-3p, miR-141-3p and miR-378a-3p demonstrated area under curve of greater than 0.9 in predicting active CD patients. Conclusion We report specific miRNA biomarkers identifying CD and its disease inflammation activity with relation to biologics use, suggesting potential treatment target in CD pathogenesis. These miRNA signatures could also be of potential clinical use in positioning biologics, which we intend to explore in the near future.

P795 Impact of anxiety and depression on inflammatory bowel disease patients

Abstract Background IBD patients may complain of stress and emotional disorders (anxiety and depression), impacting their quality of life. Anxiety and depression has been reported to be more common in IBD than in the general population. The aim of study was to estimate the prevalence and severity of anxiety and depression among IBD patients and to identify their impact on IBD related features. Methods Consecutive IBD patients presented from January 2021 to February 2022 at our outpatient IBD clinic, were included in this study. Demographic data, disease activity scores, endoscopic scores, disease duration, localization, hospitalization, laboratory data, were collected for each patient. Based on Hospital Anxiety and Depression Scale (HADS) patients were divided in 2 groups: those with symptoms of anxiety and depression and those without. Total Mayo Score (TMS) was used to evaluate UC disease activity while Crohn’s disease activity index (CDAI) for CD patients. CD was considered active when CDAI score > 150; UC was considered active when TMS >2. Results A total of 48 IBD patients (30F: 18M), mean age 41.2±15.6 years were included. 43 (89.6%) patients were diagnosed with UC, and 5 (10.4%) with CD. Mean disease duration was 5.1±4.6 years.37.2% of UC patients were in remission, 20.9% had mild disease, 32.6% moderate, and 9.3% severe disease.40% of CD patients were in remission while 60% had active disease.27.1% of patients were anti TNF-α naïve,43.8% on cortisone, 45.8% were on adalimumab and 27.1% on infliximab treatment. Anxiety and depression symptoms were present in 45.8% and 27.1% of patients, respectively.These symptoms were found combinedin 27%of the patients. No statistically significant difference was observed on the presence and scores of anxiety and depression between UC and CD patients.Presence of anxiety was significantly associated with female gender (p=0.052), UC disease extent (p=0.078), cortisone use (p=0.077), and previous hospitalizations (p=0.01.8). A significant correlation was observed between anxiety score and CDAI score (p=0.006, r=0.971); UC Mayo score (p=0.013, r=0.376) and CRP level (p=0.053, r=0.281). Presence of depression was associated with female gender (p=0.052) and UC disease activity (p=0.097).Depression score was only associated with UC Mayo score (p=0.062). On multiple linear regression,only TMS was correlated to anxiety and depression score (p=0.022, p=0.048, respectively). Conclusion Anxiety and depression are disorders frequently encountered in IBD patients, especially among females. When anxiety and/or depression were present, IBD patients demonstrated a more active disease. Addressing these psychological problems would be helpful achieving a better treatment and quality of life.

P421 Real-world effectiveness and safety of vedolizumab induction therapy for Crohn’s disease in Poland – a prospective, observational POLONEZ II study considering patients reported outcomes

Abstract Background Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking drug, used to treat ulcerative colitis (UC) and Crohn’s disease (CD), lifelong conditions with unknown aetiology with frequent relapses and remitting course which are a burden for patients and a challenge for health care systems. We aimed to evaluate the real-world effectiveness of VDZ induction therapy for Polish patients with CD. Methods This was a multicenter, observational, prospective study involving patients with moderately to severely active CD qualified for reimbursed treatment with VDZ in 10 Polish centers between Apr 2020 and Nov 2021. The primary endpoints were clinical response (≥ 70-point reduction in Crohn's Disease Activity Index, CDAI) and remission rate (CDAI ≤ 150) at week 14. Other endpoints included changes from baseline (week 0, first dose of VDZ) to week 14 for patient-reported outcomes (PROs): quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), fatigue (Inflammatory Bowel Disease-Fatigue Self-assessment Scale, IBD-F), stool frequency (SF score) and abdominal pain score (APS). Results A total of 98 patients with CD were enrolled in the study. At baseline, the most common disease location in the cohort was ileocolonic CD (n=70/98, 72.9%). Fifty patients (51%) were on corticosteroids at week 0. Nine patients discontinued VDZ therapy before or at week 14, mainly due to lack of response (n=6/9, 66.7%). At week 14, 63.3% of patients (n=62/98) achieved clinical remission and 30% (n=15/50) steroid-free remission. Clinical response rate in overall study population was 90.8% (n=89/98). Median CDAI score decreased from 336.5 to 108.0 (p<0.001) at week 14 (Fig. 1). Declines from baseline were also observed in median CDAI sub-scores: SF score (38.0 vs 10.0; p<0.001) and APS (18.0 vs 2.0; p<0.001) (Fig. 1). At week 14, median changes from baseline scores on the IBDQ (total and all subscales) were statistically significant (p<0.001) (Fig. 2). Improvement was also observed after the VDZ 14-week treatment period in fatigue severity and frequency (p<0.01) as well as its impact on daily activities (p<0.001) based on IBD-F (Fig. 3). The percentage of patients without concomitant corticosteroids increased more than 1.5-fold from week 0 (49.0%) to week 14 (76.3%). Conclusion VDZ is effective in induction therapy and has significant impact on disease activity and Health-Related Quality of Life (HRQL) including fatigue in patients with CD.

P563 Monitoring of vedolizumab drug levels in a treat to target strategy for moderate-severe IBD (MOVE-IBD)

Abstract Background Vedolizumab is an effective drug in moderate-severe ulcerative colitis (UC) and Crohn’s disease (CD). A previous link between drug exposure and clinical response has been suggested in the literature making therapeutic drug monitoring (TDM) for vedolizumab an attractive idea to try and optimize patient outcomes. Recent data from the ENTERPRET induction study in UC presented at Digestive Diseases 2022 suggest no advantage to dose optimizing based on vedolizumab levels. Thus, there is discordance in the literature regarding the clinical relevance of vedolizumab drug levels. We aimed to clarify the utility of proactive TDM of vedolizumab trough levels in our cohort of maintenance vedolizumab patients using objective markers of disease activity in a treat to target strategy. Methods A single-centre retrospective cross sectional cohort study using proactive TDM was performed on 84 patients with moderate to severe IBD on vedolizumab maintenance therapy. All patients were receiving standard vedolizumab dosing of 300 mg every eight weeks. A vedolizumab trough drug level was paired with clinical and objective markers of disease activity. The two endpoints examined were steroid free clinical remission and objective remission. Objective remission targets were individualized for each patient using a treat to target strategy and benchmarked against a baseline abnormal test. Steroid free clinical remission was defined in Crohn’s disease as a Crohn’s disease activity index (CDAI) of < 150 and in ulcerative colitis as a partial MAYO score of < 1 in a patient off steroids. Objective remission was defined as faecal calprotectin < 150 ug/g, normal bowel wall thickness on intestinal ultrasound or magnetic resonance imaging without associated features of inflammation or absence of ulceration on colonoscopy or sigmoidoscopy within 3 months of the vedolizumab level. Results Median trough vedolizumab levels for patients were numerically higher but not statistically different in patients who had achieved steroid free clinical remission (13.3 ug/ml vs 8.89 ug/ml p = 0.544) or objective remission (15.22 ug/ml vs 10.28 ug/ml p = 0.139). See Figures 1. In addition, quartile analysis showed no statistically significant difference between quartiles of vedolizumab levels and clinical or objective remission (p = 0.822). Conclusion Trough serum vedolizumab levels in our real-life cohort of maintenance moderate severe IBD patients were not associated with clinical or objective remission. Caution should be applied to basing treatment decisions off vedolizumab maintenance levels until more data becomes available to support its routine use in clinical practice.

P506 Endoscopic and clinical outcomes of upadacitinib in patients with moderate to severe Crohn’s disease by baseline disease severity

Abstract Background Upadacitinib (UPA) is an oral selective Janus kinase inhibitor with demonstrated efficacy in induction and maintenance treatment of Crohn’s disease (CD). This post hoc analysis assessed the efficacy of UPA in patients with CD by baseline (BL) disease severity. Methods In the U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) induction studies, patients with moderate-to-severe CD and intolerance/inadequate response to biologic therapy (both studies) and/or conventional therapy (U-EXCEL) received UPA 45 mg once daily (QD) or placebo (PBO) for 12 weeks. Patients who achieved clinical response to UPA induction were re-randomised in a maintenance study (U-ENDURE, NCT03345823) to receive UPA 15 mg QD, UPA 30 mg QD, or PBO for 52 weeks. Clinical remission and endoscopic response were evaluated in subgroups stratified by BL disease characteristics: Crohn’s Disease Activity Index (CDAI), very soft/liquid stool frequency (SF), abdominal pain score (APS), and Simple Endoscopic Score for CD (SES-CD). Patients from the U-EXCEL and U-EXCEED studies were pooled for analysis. Results Among 1021 patients with moderate-to-severe CD (UPA 45 mg, n=674; PBO, n=347), week 12 clinical remission and endoscopic response rates were significantly higher for patients receiving UPA 45 mg vs PBO regardless of BL disease severity (nominal P <.01), except SES-CD <6 (UPA, n=35; all had ileal disease only per the inclusion criteria) (Figure 1). UPA efficacy rates were higher compared with PBO across BL CDAI, with variable treatment effects. Patients with lower BL SF achieved clinical remission and endoscopic response with UPA 30 mg at higher rates than those with higher BL SF at week 12 and week 52. At week 12, the absolute efficacy rates and treatment differences for clinical remission and endoscopic response were generally similar across BL APS. Patients with higher BL SES-CD (≥15) generally achieved higher rates of clinical remission and endoscopic response at week 12 with UPA vs PBO than those with lower BL SES-CD (6–14). At week 52, clinical remission and endoscopic response rates were generally higher for patients receiving UPA vs PBO and most were consistent with a dose-response relationship (Figure 2). Generally, larger treatment differences between UPA and PBO were observed for patients with the most severe disease per SES-CD. Conclusion UPA induction and maintenance therapy improved clinical and endoscopic outcomes vs PBO in patients with moderate-to-severe CD, across levels of disease severity. Data for the small subgroup of patients with SES-CD <6 should be interpreted cautiously given lower mucosal healing rates in isolated ileal CD.1 Reference: 1. Atreya R, et al.Curr Res Pharmacol Drug Discov. 2022;3:100097.

P218 It is time to grow up: readiness is associated with better outcomes in a prospective study of pediatric transition patients with Inflammatory Bowel Disease

Abstract Background Approximately 25% of patients with inflammatory bowel disease (IBD) are diagnosed before age 20, making the transition from paediatric to adult healthcare challenging due to the high burden of these diseases at a critical time, such as adolescence. We aimed to assess patients’ readiness to transition from paediatric to adult IBD services and the impact on clinical outcomes. We further investigated adherence and quality of life at 12 months post- structured transition clinic Methods An observational, prospective study was conducted in a tertiary adult and paediatric IBD centre including adolescent aged≥17yo with a confirmed diagnosis of IBD before 16yo and in clinical remission who underwent “structured transition”. We collected demographics and clinical data 12 months before and after the transition visit. At the time of recruitment patients filled out the Transition Readiness Assessment Questionnaire (TRAQ) and they were defined ready based on a mean TRAQ value ≥ 3.0. The Morisky Medication Adherence Scale (MMAS) and the Short Form Health Survey (SF36) Questionnaire were completed baseline and 12 months after transition clinic. Receiving operating characteristics (ROC) curve was used to determine cut-off values of TRAQ for predicting medication adherence.We further investigated which demographic and clinical parameters could predict medication adherence. Results We enrolled 60 patients in clinical remission based on Crohn’s Disease Activity Index (CDAI) score of 115±124 for CD and pMayo 2,85±1,3 for UC, who had transitioned throughout transition clinic to adult care and completed 12 months follow-up [Table1]. Overall 42 patients (70%) were considered ready for transition, with a mean TRAQ score=3,2±0,5. The number of outpatient visits(1,86±0,75vs2,28±1,2;p<0,02) as well as the number of clinical relapses (0,38±0,4vs1,06±0,9;p<0,02) and hospitalizations (0,05±0,1vs0,33±0,33;p<0,05) at 12 months were significantly lower in ready than in not-ready patients. The quality of life did not differ pre-and 12 months post-transition clinic(p=0,09) and between ready and not-ready patients (p=0,71)[Table2]. Based on ROC curve a TRAQ cut-off≥3,46 could predict medication adherence with a sensibility of 55%,specificity 86% and an AUC=0,71(0,57-0,85;p=0,008)[Fig1]. At multivariate analysis, a high mean TRAQ value was associated with medication adherence at 12 months (OR:7,042CI:1,68-29,54,p=0.008) Conclusion Patients ready for transition were more likely to have fewer outpatient visits,disease flares and hospitalizations compared to not-ready patients. The quality of life did not differ pre- and post transition and between ready and not-ready patients.TRAQ score could be a reliable tool with high specificity to predict medication adherence

P786 Induction of endoscopic response, remission and ulcer-free endoscopy with upadacitinib is associated with improved clinical outcomes in patients with Crohn’s disease

Abstract Background STRIDE-II guidelines recommend endoscopic healing as an important treatment goal in Crohn’s disease (CD). This study evaluated the association of achieving endoscopic outcomes at week 12 and clinical outcomes at week 52 of maintenance treatment in patients with CD treated with upadacitinib (UPA). Methods This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and the maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Clinical outcomes (CD activity index [CDAI] remission, CDAI response, steroid-free CDAI remission, high sensitivity C-reactive protein [hs-CRP] level ≤5 mg/L, and fecal calprotectin level [F-cal] ≤250 mcg/g), were evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test. Results Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.3%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained clinical outcomes at week 52 (CDAI remission, 52.0% vs 34.6%; CDAI response, 54.6% vs 39.5%; hsCRP ≤5 mg/L, 52.0% vs 30.8%; and F-cal ≤250 mcg/g, 42.1% vs 21.6%; P≤0.01, Table 1). Patients who achieved an endoscopic response vs those who did not at end of induction were also more likely to attain steroid-free CDAI remission (50.0% vs 30.9%) at week 52, (P≤0.05, Table 1). Similar findings were observed in patients who achieved endoscopic remission vs those who did not at end of induction (P≤0.01, Table 1). Significantly more patients attained CDAI remission (58.7% vs 37.7%), CDAI response (58.7% vs 42.7%), hsCRP ≤5 mg/L (58.7% vs 35.0%) and F-cal ≤250 mcg/g (50.7% vs 25.0%) at week 52, among patients who achieved ulcer-free endoscopy vs those who did not at end of induction (P≤0.05, Table 1). Conclusion Achieving endoscopic outcomes at end of induction is associated with meaningful improvement in symptoms and inflammatory biomarkers at 52 weeks for patients with CD receiving UPA therapy. Endoscopic remission and ulcer-free endoscopy are associated with very similar long-term benefits.

Diarrhea-predominant Irritable Bowel Syndrome-like Symptoms in Patients With Quiescent Crohn's Disease: Comprehensive Analysis of Clinical Features and Intestinal Environment Including the Gut Microbiome, Organic Acids, and Intestinal Permeability.

Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms frequently occur in patients with quiescent Crohn's disease (CD). To investigate the factors underlying IBS-D-like symptoms in patients with quiescent CD, we performed a comprehensive analysis of the clinical features and intestinal environment in those patients. We performed a prospective observational study of 27 patients with quiescent CD (CD activity index [CDAI] ≤ 150; C-reactive protein ≤ 0.3 mg/dL). The presence and severity of IBS-D-like symptoms, health-related quality of life, disease-specific quality of life, and status of depression and anxiety were evaluated. The level of intestinal permeability, fecal calprotectin and organic acids and the profiles of gut microbiome were analyzed. Twelve of the 27 patients with quiescent CD (44.4%) had IBS-like symptoms, and these patients showed a significantly higher CDAI, IBS severity index and anxiety score than those without. The inflammatory bowel disease questionnaire score was significantly lower in the patients with IBS-D-like symptoms. There were no significant differences in small intestinal/colonic permeability or the levels of organic acids between the patients with and without IBS-D-like symptoms. Fusicatenibacter was significantly less abundant in the patients with IBS-D-like symptoms whereas their fecal calprotectin level was significantly higher (384.8 ± 310.6 mg/kg) than in patients without (161.0 ± 251.0 mg/kg). The receiver operating characteristic curve constructed to predict IBS-D-like symptoms in patients with quiescent CD using the fecal calprotectin level (cutoff, 125 mg/kg) showed a sensitivity and specificity of 73.3% and 91.7%, respectively. Minimal inflammation is closely associated with the development of IBS-D-like symptoms in patients with quiescent CD.

P354 Application of the clinical decision support tool to predict treatment outcomes in Crohn’s Disease patients treated with vedolizumab subcutaneous formulation

Abstract Background There is a need to identify Crohn’s Disease (CD) patients who will obtain most clinical benefit from treatment with vedolizumab (VDZ), an anti-α4β7 integrin inhibitor for the treatment of ulcerative colitis and Crohn’s Disease (CD). Previously, a clinical decision support tool (CDST) has been developed and validated to guide treatment decisions in CD patients (pts) treated with intravenous VDZ.1 In this study, we aimed to test the ability of the CDST to predict clinical outcomes in CD pts receiving maintenance treatment with the subcutaneous (SC) formulation of VDZ. Methods Pts with moderate to severe CD receiving maintenance treatment with VDZ SC in the VISIBLE 2 study were categorized using the CDST into low (≤13 points), intermediate (>13 and ≤19 points) and high response probability groups (>19 points) based on the scoring system detailed in Table 1. Clinical outcomes evaluated included clinical remission: CD Activity Index (CDAI) ≤ 150 at Week 6, 14, 30, and 52, and enhanced clinical response: decrease from baseline in CDAI score ≥ 100 points at Week 52. All outcomes were evaluated as observed. Results There were 275 pts who completed induction treatment with VDZ 300 mg IV and continued into maintenance treatment with VDZ 108 mg SC until Week 52. Using the CDST, at baseline, 14 pts (5.1%) had a low, 98 (35.6%) had an intermediate, and 163 (59.3%) had a high probability of treatment response with VDZ. Due to the low number of pts in the low probability group, the low and intermediate groups were combined. At Week 6, 99 pts (61.1%) in the high probability group had achieved clinical remission vs 38 pts (33.9%) in the low/intermediate probability group (Fig 1). Rates of clinical remission in the high probability group continued to exceed those of the low/intermediate group through until Week 52 when 89 pts (86.4%) in the high probability group were in clinical remission vs 43 pts (79.6%) in the low/intermediate probability group (Fig 1). In the high probability group, 97 pts (94.2%) had an enhanced clinical response at Week 52 compared with 46 pts (85.2%) in the low/intermediate group. Conclusion Compared with the low/intermediate group, pts categorized by the CDST as having the highest probability of treatment response to VDZ achieved clinical remission sooner, as early as Week 6. These findings provide further confirmation of the CDST as a means of identifying pts with CD likely to benefit from treatment with VDZ in either IV or SC formulations.

P548 Efficacy outcomes of placebo maintenance treatment in patients with moderate to severe Crohn’s disease who responded to placebo induction therapy: Post-hoc analysis of the Phase 3 ADVANCE, MOTIVATE, and FORTIFY Risankizumab Studies

Abstract Background In the risankizumab (RZB) phase 3 clinical programme, Crohn’s disease (CD) patients who responded to RZB intravenous (IV) induction were re-randomised to RZB or placebo (PBO) (withdrawal PBO subcutaneous [SC] in maintenance (FORTIFY), while responders to PBO induction continued receiving PBO. Patients in the withdrawal (PBO SC) arm of FORTIFY who received IV RZB induction achieved high rates of clinical response/remission at Week (Wk) 52 likely due to the prolonged PK/PD effect of RZB and robust efficacy during induction.1 Here, we describe disease activity outcomes in non-randomised patients who received PBO during both induction and maintenance. Methods: This post-hoc analysis included patients who received PBO IV in the induction study (ADVANCE or MOTIVATE), achieved clinical response (definition in Figure footnote) at Wk 12, and continued on PBO SC during FORTIFY.1,2 Subjective measures of disease activity (clinical remission [per CD Activity Index (CDAI)] and per stool frequency [SF] and abdominal pain score [APS], CDAI clinical response, and SF/APS enhanced clinical response), as well as objective measures of biomarkers (high sensitivity C-Reactive Protein and faecal calprotectin) levels and endoscopic outcomes (response, remission, and ulcer-free endoscopy), during FORTIFY were evaluated (endpoint definitions in Figure footnotes) at Wk 52. Biomarkers were additionally evaluated at induction baseline. For reference only, previously reported data from patients who were clinical responders to RZB IV induction and were re-randomised in FORTIFY are presented alongside data from the continuous PBO patients subgroup.1,2 Results In the 104 patients who received PBO during both induction and maintenance, clinical response and remission rates decreased steadily during FORTIFY (Figure), while biomarker levels were relatively unchanged from induction baseline to FORTIFY Wk 52. In contrast, a slower rate of loss of response per clinical response/remission and lower biomarker levels over time were observed in RZB IV induction responders re-randomised to PBO in FORTIFY. Although already low, endoscopic response rates in the continuous PBO group decreased from FORTIFY Wk 0 to Wk 52, whereas endoscopic remission and ulcer-free endoscopy rates remained unchanged. Conclusion The symptomatic improvement achieved in patients clinically responding to PBO during induction was not maintained with continued PBO treatment in maintenance, unlike that observed in patients withdrawn from RZB, underscoring the durability of RZB induction response.1 Most objective measures of disease activity in patients receiving continuous PBO were relatively unchanged over time, with biomarkers remaining elevated and endoscopic rates of response low.

P473 Corticosteroid-free clinical remission rates with guselkumab maintenance therapy in patients with moderately to severely active Crohn’s disease: Week 48 analyses from the phase 2 GALAXI 1 study

Abstract Background Corticosteroids are often used in Crohn’s disease (CD) to control inflammation. However, they are associated with adverse events; thus, achieving and maintaining remission without corticosteroids is a major treatment goal. GALAXI 1, a phase 2b, double-blind, placebo (PBO)-controlled study, evaluated efficacy and safety of guselkumab (GUS), a selective interleukin-23p19 subunit antagonist, in patients (pts) with moderately to severely active CD. Primary efficacy and safety data were presented previously. Here, we report corticosteroid-free clinical remission rates through Week (Wk) 48. Methods Pts with moderately to severely active CD were randomised in a treat-through design to GUS 200, 600, 1200mg; ustekinumab (UST) ~6mg/kg; or PBO intravenous (IV) induction followed by maintenance dosing (GUS 200mg IV-->GUS 100mg subcutaneous [SC] every 8 weeks [q8w], GUS 600mg IV-->GUS 200mg SC q4w, GUS 1200mg IV-->GUS 200mg SC q4w, UST ~6mg/kg IV-->UST 90mg SC q8w, PBO nonresponders-->UST ~6mg/kg IV-->UST 90mg SC q8w, PBO responders-->PBO SC q4w). Corticosteroid tapering was mandatory from Wk12 if medically feasible. Efficacy endpoints included corticosteroid-free CD Activity Index (CDAI) clinical remission (<150) and pt-reported outcome (PRO)-2 remission at Wk48 in the primary efficacy population. Pts randomised to PBO were not included in Wk48 efficacy analyses. GALAXI 1 was not powered to evaluate efficacy differences between treatment groups at Wk48; UST was a reference arm. Analyses were prespecified but not multiplicity controlled. Results At Wk48, 55.7-71.4% of pts in the GUS dose groups achieved corticosteroid-free CDAI clinical remission (Table 1). Similar rates were observed when the corticosteroid-free duration was ≥30 or ≥90 days before Wk48. Among pooled pts in CDAI clinical remission at Wk48 in the GUS groups, 115/120 (95.8%) were corticosteroid free. At Wk48, 49.2-68.3% of pts in the GUS dose groups achieved corticosteroid-free PRO-2 remission (Table 1). Among pooled pts in PRO-2 remission at Wk48 in the GUS groups, 105/110 (95.5%) were corticosteroid free. Outcomes in the reference UST group are shown in Table 1. Among pts in the GUS dose groups, 30.2-39.3% were using corticosteroids at Wk0 (median prednisone equivalent dose 20.0mg/d in each group); at Wk48, 60.0-78.9% of these pts met corticosteroid-free criteria (Table 2). Conclusion High rates of corticosteroid-free CDAI clinical and PRO-2 remission were achieved at Wk48 in the GUS dose groups. Among pts in clinical remission, most were corticosteroid free. Nearly all pts maintained corticosteroid-free CDAI clinical remission for ≥90 days. GUS IV induction followed by SC maintenance therapy also effectively reduced corticosteroid use at Wk48.

P716 A 2-week course of Exclusive Enteral Nutrition followed by the Crohn Disease Exclusion Diet is effective for Induction and Maintenance of Remission in children with Crohn Disease; the DIETOMICS-CD trial

Abstract Background Exclusive enteral Nutrition (EEN) is considered a first line therapy for children with active Crohn disease (CD). CD Exclusion Diet (CDED)+Partial Enteral Nutrition (PEN) is effective for induction of remission in mild-moderate CD at weeks 6 and 12, with better tolerance than EEN. We assessed whether a 2-week course of EEN, followed by CDED+PEN is superior to 8 weeks of EEN in sustaining clinical remission at week 14, outcomes of CDED up to 24 weeks, and the utility of CDED in mild-severe CD. Methods This international, multicenter, randomized-controlled trial compared 2 weeks of EEN (Modulen, Nestle Health Science) followed by 3 phases of the CDED+PEN to 8 weeks of EEN, followed by PEN with free diet, both up to week 24. Children aged 8-18 with CD<3 years, mild-severe disease [paediatric CD activity index (PCDAI) 15-47.5], and active inflammation [elevated C-reactive protein (CRP) or faecal calprotectin (FCP)] were included. Stable immunomodulator (IM) treatment was allowed. Naïve patients were allowed to start an IM from week 4. Results Of the 63 eligible patients enrolled, 55 were randomized and included in the final intention to treat analysis (target recruitment failed due to COVID); Group 1 (CDED+PEN;29) and group 2 (EEN;26), mean age 12.7±2.4. Steroids-free sustained remission at week 14 was obtained in 20/29(69%) in group 1 and 16/26(61.5%) in group 2, p=0.56. Remission at week 8 was obtained in 22/29(76%) in group 1 and 14/26(54%) in group 2, p=0.08. 16/29(55%) in group 1 and 9/26(34%) in group 2 maintained clinical remission at week 24; p=0.12. Median PCDAI declined from 32.5[20-36.2] to 2.5[0-5.6] and 1.2[0-5.6] in group 1 (p<0.001 for all), and from 22.5[20-29.3] to 0[0-4.3] and 0[0-2.5] in group 2 (p<0.005 for all) at baseline, week 8 and 14 respectively. Median CRP improved in group 1 from 32 mg/L[6-69] to 5[2-16] and 3[2-10.1] (p<0.001 for both) and in group 2 from 10.35 mg/L[5-33] to 3.7[2.2-7.2], p=0.012 and 3.2[2.8-5], p=0.006 at baseline, week 8 and 14 respectively. Median FCP declined in group 1 from 1946 µg/g [862-3304] to 802[196-1312] at week 8 and 241[82-1175] at week 14 (p<0.01 for both), and in group 2 from 1615[605-2692] at baseline to 436[252-1389] at week 8, which then increased to 731[349-1305] at week 14 (p<0.01 for both). At week 14, 12/22(54%) received IM from group 1 and 15/16(93%) from group 2; p= 0.009. Conclusion Two weeks of EEN followed by CDED&PEN and EEN were successful in induction of clinical and biochemical remission in mild-severe paediatric CD, and most CDED+PEN patients-maintained remission to 24 weeks. Sustained clinical remission at week 14 was similar despite higher IM use in the EEN Group, suggesting that CDED might prevents diet-induced inflammation regardless of IM use.

P879 Clinical significance of plasma interleukin-22 as a biomarker of inflammation in patients with Crohn’s disease and ulcerative colitis

Abstract Background IL-22 is a key cytokine in the pathogenesis of inflammatory bowel disease (IBD). While evidence underpinning its central role as a biomarker of pathway activation, diagnosis, severity and activity for IBD has been accumulating, little is known about its application as a biomarker in IBD in real-world practice. Here, we characterize for the first time the relationship between IL-22 plasma concentrations and the clinical characteristics of a large, real-world population of patients with IBD. Methods This is a descriptive analysis of patients in the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus registry of the Crohn’s & Colitis Foundation in the United States. The SPARC registry includes patients with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). This study evaluated baseline data collected within ± 30 days from consent date. Assessments included demographics, clinical characteristics and IL-22 plasma concentrations. Disease severity was assessed using short CD Activity Index (sCDAI; scores <150 define remission, 150–219 mild activity, ≥220 moderate-severe activity) or 6-point UC Disease Activity Index (UCDAI; scores ≤1 define remission, 2–3 mild activity, ≥4 moderate-severe activity) disease severity categories. Results A total of 2667 patients with CD and 1326 patients with UC were eligible for inclusion in the study. For patients with CD, median age was 39 years, 57% were female and median disease duration was 13 years (Table 1). For patients with UC, median age was 40 years, 51% were female and median disease duration was 9 years (Table 1). In total, 1604 patients with CD and 836 patients with UC had valid IL-22 samples at baseline, of which 33% and 25%, respectively, were above the lower limit of quantification (LLOQ; 7.8 pg/mL). There was a trend toward fewer patients with IL-22 levels below the LLOQ among patients with high disease severity compared with those with lower disease severity both in patients with CD and those with UC (Figure 1). Additionally, there was an increase in the percentage of patients with IL-22 levels greater than the third quartile (overall Q3 = 10.8 pg/mL in CD, and = 7.9 pg/mL in UC) with increased disease severity (Figure 2). Comparison of subgroups of patients with low and medium/high IL-22 levels showed a consistent pattern with fewer patients in remission and more moderate-severe patients in the medium/high IL-22 group than in the low IL-22 group (Table 2). Conclusion Higher IL-22 levels tended to be associated with higher disease activity in this real-world population of IBD patients.

P448 Long term effectiveness of first-line infliximab treatment compared to conventional treatment in paediatric moderate-to-severe Crohn’s disease – an update from the TISKids study

Abstract Background Current guidelines recommend first-line anti-TNF therapy (start at diagnosis) only in children with high risk for a complicated disease course. However, previous results of the TISKids study showed that first-line infliximab (FL-IFX) treatment (5 infusions in total) combined with azathioprine (AZA) was more effective to achieve clinical remission without treatment escalation at week 52 compared to conventional induction treatment (CONV) with AZA in therapy-naïve children with moderate-to-severe CD, irrespective of having high risk for development of complications1. The aim of our study was to investigate the effects at 3-year follow-up of the TISKids cohort. Methods The TISKids study is a multicentre, open-label randomised controlled trial in which untreated patients with a new diagnosis of CD (3–17 years old, weighted paediatric CD activity index score >40) were included. Patients were randomised to FL-IFX (5 infusions of 5 mg/kg infliximab at weeks 0, 2, 6, 14, 22) or CONV (EEN or prednisolone). Both treatment groups were combined with AZA maintenance. The primary outcome was biochemical remission (faecal calprotectin <250 ug/g) without need for additional biological treatment at 3 years. Secondary outcomes were time to additional biological treatment and number of patients with luminal surgery until 3 years. Additional biological treatment in the FL-IFX group included intensification, continuation or restart of IFX. Differences in proportions were tested using the Chi-square or Fisher-exact test, time to additional biological was analysed using Kaplan-Meier method with log-rank test. Results In total, 50 patients received FL-IFX and 47 CONV. One patient from each group was lost to follow-up, data at 3 years was available in 89/97 patients. At 3 years, 5/43 (12%) FL-IFX patients were in biochemical remission without need for additional biological treatment compared to 4/42 (10%) CONV patients (p=1.00). The time to additional biological treatment was significantly longer for the FL-IFX patients (median 63 weeks) compared to CONV patients (median 32 weeks), p=0.019. The number of luminal surgeries (all ileocaecal resections) until 3 years was not significantly different between FL-IFX (n=2/46, 4%) compared to CONV (n=5/43, 12%), p=0.256. Conclusion These results imply that there still is a significant benefit of FL-IFX during 3 years of follow-up (longer time to additional biological treatment compared to CONV), demonstrating durability of providing effective induction treatment. Further research should identify in which patient and when IFX may be stopped and which maintenance treatment would be appropriate in order to sustain and further optimize the benefits of FL-IFX treatment. 1. Jongsma MME et al. Gut. 2020. PMID: 33384335

METHODS TO DERIVE A CROHN'S DISEASE ACTIVITY INDEX FROM ELECTRONIC HEALTH RECORDS DATA

Abstract BACKGROUND The Crohn’s Disease Activity Index (CDAI) is currently the gold-standard for measuring disease activity in Crohn’s disease (CD) patients. It is the most commonly used outcome measure in clinical trials, however, due to the burden of completion, it is infrequently used in routine care. Real world data, including electronic health records (EHR), are useful for studying longitudinal disease and treatment outcomes in the real world, but most EHR databases do not include CDAI. Building off the methods presented by Rudrapatna et al. 2021, we calculated a derived CDAI using data elements available in EHRs. METHODS Data were derived from the OM1 PremiOM UC Dataset (OM1, Boston, MA), a multisource real-world database with linked healthcare claims and EHR data on US patients with CD (2013-present). Weight, body temperature and hematocrit were sourced from structured vital signs and laboratory data. Ideal body weight was calculated from height and gender using the Devine formula. Extraintestinal manifestations/complications were evaluated based on the presence or absence of ICD diagnosis codes for each condition. Abdominal mass was abstracted from clinical notes. Number of stools in the past 7 days, average daily abdominal pain, and general well being were extrapolated from single-day measures extracted from clinical notes rather than based on 7-day diaries. Each component value was multiplied by the weights outlined in Best et al. 1976. Components recorded within 4 months were added to calculate a derived CDAI. Multiple CDAIs could be calculated for each patient over time, but each component was allowed to contribute to only one CDAI score. RESULTS Among 13,159 CD patients, only 12 had a CDAI recorded in their notes. After applying the algorithm, we were able to calculate a derived CDAI for 1,378 patients. 489 patients had > 1 score derived. Figure 1 shows the distribution of derived CDAIs. Patients with a derived CDAI were younger and a higher proportion were treated with biologics and corticosteroids than those who could not have a CDAI calculated (Table 1). CONCLUSIONS A derived CDAI can be calculated from data that may be routinely recorded in EHRs. Efforts to standardize the collection of CDAI components in EHRs would further increase the availability of derived CDAIs. Further work to validate these derived scores against a gold standard and to replicate the findings in other real-world datasets should be considered. Validation was not feasible in this dataset due to the lack of recorded CDAIs. Derived CDAIs could potentially be used to study longitudinal changes in disease status and treatment effectiveness in settings where observed CDAIs are unavailable.

TRENDS AND RELATED FACTORS OF QUALITY OF LIFE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract INTRODUCTION Inflammatory bowel disease(IBD) affects health-related quality of life(HRQoL). The short inflammatory bowel disease questionnaire(SIBDQ), measuring physical, social, and emotional status(score 10-70, poor to good HRQoL), is known to be well correlated to HRQoL of IBD patients. AIM/METHODS We aimed to evaluate factors that impact IBD patients' HRQoL. This prospective study included a cohort of patients with ulcerative colitis(UC) and Crohn’s disease(CD). IBD patients completed a SIBDQ questionnaire at enrollment and 20% of those patients completed a second SIBDQ questionnaire at follow-up. Data were analyzed using multiple linear regression analysis and Pearson’s correlation. RESULTS A total of 1,058 patients with IBD(UC 68%, CD 32%) were included. A SIBDQ score was median 52(IQR: 44-58). The first and follow-up SIBDQ score were not significantly different between UC and CD patients (p=0.243 and p=0.893, respectively). The distributions of SIBDQ change were as follows: decrease over 10%: 28%, -10% < change < 10%: 29%, increase over 10%: 43%. In UC patients, significant factors that negatively associated with SIBDQ score, were physician’s global assessment(r=-3.562, p<0.001), corticosteroids use(r=-5.478, p<0.001), fecal calprotectin level(r=-2.313, p=0.008), presence of joint symptoms(r=-2.925, p=0.017). In CD patients, significant factors that negatively associated with SIBDQ score, were Crohn's disease activity index score(r=-0.035, p=0.009), level of abdominal pain(r=-3.400, p=0.013) and presence of skin symptoms(r=-3.842, p=0.016). Factors that associated with SIBDQ score in both UC and CD patients were stool frequency(r=-2.913, p<0.001 in UC patients; r=-2.347, p=0.014 in CD patients). CONCLUSION SIBDQ questionnaire shows that IBD patients' HRQoL was mainly affected by the patient-reported outcome. However, it was also influenced by biochemical markers and extraintestinal symptoms depending on the specific type of IBD.

68Ga]Ga-FAPI-04 PET/CT on assessing Crohn's disease intestinal lesions.

Fibrosis and inflammation are major pathological changes of Crohn's disease (CD). Early detection and accurate severity evaluation of CD are critical for patient's prognosis. Endoscopy is widely used to evaluate CD progression. Herein, we evaluated the efficacy of [68Ga]Ga-FAPI-04 PET/CT to identify lesions and assess the progression of CD. All CD patients received computed tomography enterography (CTE), [68Ga]Ga-FAPI-04 PET/CT examination, and ileocolonoscopy within 1week. Two independent gastroenterologists computed the Crohn's disease activity index (CDAI) of all patients. Two radiology physicians assessed the CTE images separately, and the CTE scores were calculated. Lastly, two nuclear medicine physicians independently examined the [68Ga]Ga-FAPI-04 PET/CT images. Once the FAPI uptake of the intestinal segment was equal or higher relative to the liver (considered FAPI-positive), the target-to-background ratio (TBR) and global FAPI PET/CT score were computed, representing the independent intestinal activity and activity of all intestinal segments, respectively. Levels of fecal calprotectin (FCP) and C-reactive protein (CRP) were determined before the endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) and the simple endoscopic score for Crohn's disease (SES-CD) were calculated during the endoscopy. Finally, all data were obtained and analyzed. There were 74 intestinal segments in 16 patients were assessed. [68Ga]Ga-FAPI-04 PET/CT identified 42 of 45 endoscopically lesioned segments (endoscopic lesions detection sensitivity: 93.3%), while CTE identified 39 of them (endoscopic lesions detection sensitivity: 86.7%). According to the receiver operating characteristic (ROC) analysis, [68Ga]Ga-FAPI-04 PET/CT showed better performance in the detection of endoscopic lesions compared with CTE (P < 0.05). The TBR was significantly associated with the CTE score (r = 0.81; (95% CI): 0.736-0.869; P < 0.0001) and SES-CD values (r = 0.86; (95% CI): 0.776-0.908; P < 0.0001). In addition, the global FAPI PET/CT score was significantly correlated with FCP (r = 0.52; 95% CI, 0.02-0.81; P = 0.039), CRP (r = 0.60; 95% CI, 0.13-0.85; P = 0.014), CDEIS (r = 0.55; 95% CI, 0.06-0.83; P = 0.028), and CDAI (r = 0.81; 95% CI, 0.50-0.93;P < 0.0001). In summary, [68Ga]Ga-FAPI-04 PET/CT correlated well with endoscopic, CTE, clinical, and biomarkers of CD. It was also highly sensitive in the detection of different classes of lesions in all intestinal segments, and unlike other examinations, this technique required no patient fasting or bowel preparation. Therefore, [68Ga]Ga-FAPI-04 PET/CT may be a promising method for assessing the activity of CD.

Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1weeks. This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.

Contrast-Enhanced Ultrasonography for the Evaluation of Crohn's Disease in Pediatric Patients.

Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn's disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn's disease activity in children with endoscopy as the reference standard. In this prospective study, 30 pediatric patients with Crohn's disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021. The simple endoscopic score for Crohn's disease, pediatric Crohn's disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings. CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn's disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn's disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015). CEUS can be a safe and specific diagnostic modality for Crohn's disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn's disease.