Changes In Crohn's Disease Activity Index Research Articles

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.

S0705 Evaluation of Symptom Improvement During Induction in Patients With Crohn's Disease Treated With Mirikizumab

INTRODUCTION: Mirikizumab (miri), a humanized, IgG4 monoclonal antibody that targets IL23, has shown efficacy and safety in patients treated for Crohn's disease (CD), psoriasis, and ulcerative colitis. In a phase 2, randomised, parallel-arm, placebo-controlled study, symptom improvement was evaluated in patients with moderately-to-severely active CD after intravenous induction treatment with miri (NCT02891226). METHODS: Entry criteria for enrollment included an average daily stool frequency (SF; ≥ 4) and/or the average daily occurrence of abdominal pain (AP; ≥ 2) from the Crohn's Disease Activity Index (CDAI), and a Simple Endoscopic Score for CD ≥ 7 in patients with ileal-colonic or ≥ 4 in patients with isolated ileal disease. Patients were randomised 2:1:1:2 to receive intravenous miri (200 mg, 600 mg, or 1,000 mg) or placebo at weeks 0, 4, and 8. Endpoints in this analysis included changes from baseline in CDAI, SF, and AP at weeks 4, 8, and 12. A mixed effects model for repeated measures analysis was conducted to compare mean changes from baseline across treatment groups for the all-patient cohort and for the biologic-experienced sub-group. Factors in the analysis included treatment, geographic region, baseline score, prior biologic CD therapy (all-patient cohort), visit, and treatment by visit interaction as fixed effects. An unstructured variance covariance was used. RESULTS: A total of 191 patients were randomised at baseline, which included biologic naïve (n = 71) and biologic-experienced patients (n = 120). Changes in CDAI, SF, AP at weeks 4, 8 and 12 compared to baseline are shown in the Table. In the all-patient cohort, statistically significant improvement in CDAI was observed with miri 600 mg and in SF with miri 200 mg compared to placebo as early as week 4 (Table). Improvement in CDAI and SF occurred with all miri doses (200 mg, 600 mg, 1,000 mg) at weeks 8 and 12 and in AP at weeks 8 and 12 with all miri doses. Compared to placebo, the subgroup of biologic-experienced patients showed statistically significant improvement in CDAI at week 4 (miri 600 mg) and at weeks 8 and 12 with all three doses. Further, significant improvement was observed in SF at week 12 (miri 600 mg and miri 1,000 mg) and in AP at week 8 (miri 600 mg) and week 12 (miri 600 mg and miri 1,000 mg). CONCLUSION: Treatment with miri induced early improvement in clinical symptoms and disease activity in patients with moderately-to-severely active CD.Table 1: Treatment Effect of Mirikizumab vs Placebo in Reducing Crohn's Disease Activity Index, Stool Frequency, and Abdominal Pain Over Time

Efficacy of Mesenchymal Stromal Cells for Fistula Treatment of Crohn's Disease: A Systematic Review and Meta-Analysis.

The introduction of mesenchymal stromal cells (MSCs) has changed the management of Crohn's fistula, while it remains controversial. The aim of this study was to provide an overview of efficacy and optimum state of MSCs treatment on Crohn's fistula. Studies reporting MSCs treatment on Crohn's fistula were searched and included. A fixed-effects model was used to assess the efficacy of MSCs, and outcomes of healing and recurrence were used to evaluate the best states of MSCs intervention. Fourteen articles were enrolled (n=477). Pooled analysis showed MSCs had a significant efficacy compared to other treatments [risk difference: 0.21 (0.09, 0.32), P=0.000]. Notably, after MSCs treatment, the group of Crohn's disease activity index (CDAI) baseline >150 group had a higher healing rate (HR) and a clinical response (a change in CDAI of >50 points) (79.17±8.78 vs. 47.54±15.90, P=0.011) compared to CDAI baseline of <150. The duration time of CD and fistulas had a negative correlation with HR accompanied by MSC therapy (r=-0.900, -0.925). Then, a moderate dose MSCs (2-4×107cells/ml) had a higher HR (80.07%) and lower recurrence rate (RR 13.98%) compared to other dosages. Moreover, adipose-derived MSCs therapy had an advantage over bone marrow-derived MSCs in terms of low RR (7.4±4.28 vs. 13.39±0.89). The evidence supported the effect of MSCs at a more appropriate time of Crohn's fistula. And CDAI baseline (the points >150) has been a candidate for evaluating effectiveness of MSCs application on Crohn's fistula.

Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a randomised controlled trial

ObjectiveAnti-NKG2D (NNC0142-0002) is an antagonising human immunoglobulin G4 monoclonal antibody that binds to natural killer group 2 member D (NKG2D) receptors, which are expressed by T cells and innate lymphoid...

Budesonide for induction of remission in Crohn's disease.

Corticosteroids are commonly used for the induction of remission in Crohn's disease. However, traditional corticosteroids can cause significant adverse events. Budesonide is an alternative glucocorticoid with limited systemic bioavailability. The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease. The following electronic databases were searched up to June 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. Randomised controlled trials comparing budesonide to a placebo or active comparator were considered for inclusion. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Meta-analysis was performed using RevMan 5.3.5 software. The primary outcome was induction of remission (defined by a Crohn's disease activity index (CDAI) < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal. We calculated the relative risk (RR) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome and the mean difference and corresponding 95% CI for each continuous outcome. Data were analyzed on an intention-to-treat basis. A random-effects model was used for the pooled analyses. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was evaluated using the GRADE criteria. Fourteen studies (1805 patients) were included: Nine (779 patients) compared budesonide to conventional corticosteroids, three (535 patients) were placebo-controlled, and two (491 patients) compared budesonide to mesalamine. Ten studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to open label design. One study was judged to be at high risk of bias due to selective reporting. After eight weeks of treatment, 9 mg budesonide was significantly more effective than placebo for induction of clinical remission. Forty-seven per cent (115/246) of budesonide patients achieved remission at 8 weeks compared to 22% (29/133) of placebo patients (RR 1.93, 95% CI 1.37 to 2.73; 3 studies, 379 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (144 events). Budesonide was significantly less effective than conventional steroids for induction of remission at eight weeks. Fifty-two per cent of budesonide patients achieved remission at week 8 compared to 61% of patients who received conventional steroids (RR 0.85, 95% CI 0.75 to 0.97; 8 studies, 750 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to risk of bias. Budesonide was significantly less effective than conventional steroids among patients with severe disease (CDAI > 300) (RR 0.52, 95% CI 0.28 to 0.95). Studies comparing budesonide to mesalamine were not pooled due to heterogeneity (I(2) = 81%). One study (n = 182) found budesonide to be superior to mesalamine for induction of remission at 8 weeks. Sixty-eight per cent (63/93) of budesonide patients were in remission at 8 weeks compared to 42% (37/89) of mesalamine patients (RR 1.63, 95% CI 1.23 to 2.16). The other study found no statistically significant difference in remission rates at eight weeks. Sixty-nine per cent (107/154) of budesonide patients were in remission at 8 weeks compared to 62% (132/242) of mesalamine patients (RR 1.12, 95% CI 0.95 to 1.32). Fewer adverse events occurred in those treated with budesonide compared to conventional steroids (RR 0.64, 95% CI 0.54 to 0.76) and budesonide was better than conventional steroids in preserving adrenal function (RR for abnormal ACTH test 0.65, 95% CI 0.55 to 0.78). Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although short-term efficacy with budesonide is less than with conventional steroids, particularly in those with severe disease or more extensive colonic involvement, the likelihood of adverse events and adrenal suppression with budesonide is lower. The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-ASA products.

Su1083 Can Crohn's Disease Activity Index Differentiate Clinical Remission Induced by Placebo Versus Biologics Treatment? – Analyses of Six Clinical Trials for Crohn's Disease

Crohn's Disease Activity Index (CDAI), a composite score based on eight subcomponents, has been used to assess the efficacy of drugs for Crohn's Disease (CD). However, the existence of a high placebo rate has been a challenge in clinical trials that have used CDAI as the primary endpoint. To better understand the placebo effect, we evaluated the change from baseline in CDAI and its subcomponents in patients who achieved remission in response to placebo or active treatment. Patient-level data were reviewed from six phase 2 and phase 3 clinical trials that were submitted to FDA in support of three biological products for treatment of CD. Clinical remission was defined as CDAI < 150 in all six trials, and the induction of remission was assessed at a pre-defined time-point. We evaluated the overall change from baseline in CDAI and its subcomponents in achieving remission and identified major contributing subcomponents. We compared changes in CDAI and major contributing subcomponents in patients who achieved remission by placebo or active treatments. Mean baseline CDAI across trials ranged from 294 to 313 in placebo groups and 295 to 312 in active treatment groups. The rate of remission ranged from 8.2% to 30.3% among the placebo groups and 22.2% to 39.6% among the active treatment groups across six trials. For remitters, the average decrease from baseline in CDAI score was 167 in the placebo groups and 186 in active treatment groups across six trials. Greater than 80% of the decrease in the overall CDAI score was attributed to a decrease in three subcomponent scores: general well-being [WB] (40%), abdominal pain [AP] (25%), and stool frequency [SF] (22%). The relative contribution of each subcomponent to achieve remission was similar between placebo

Budesonide for Maintenance of Remission in Crohnʼs Disease: Update of a Systematic Review and Meta-analysis for the Cochrane Collaboration

Purpose: Budesonide (BUD) has been shown to be effective for induction of remission in Crohn's disease (CD), but concerns have been raised about the efficacy and safety of its long-term use. This systematic review and meta-analysis examined the efficacy and safety of BUD for maintenance of remission in CD. Methods: MEDLINE, EMBASE, other electronic databases, article reference lists, and conference proceedings were searched up to January, 2013 to identify randomized controlled trials on BUD. Those comparing BUD to a control treatment or comparing two doses of BUD were included. The primary outcome was maintenance of remission at one year. Secondary outcomes included mean change in CD activity index (CDAI), adverse events, and study withdrawal. Two independent investigators reviewed studies for eligibility and extracted the data. For the meta-analysis, a random or fixed effects model was chosen based on an assessment of heterogeneity. Results: Twelve studies were identified. Only one additional study was found since the previous review, which compared azathioprine with BUD. BUD 6 mg daily was no more effective than placebo for maintenance of remission at 3 months (RR 1.25, 95% CI 1.00-1.58), 6 months (RR 1.15, 95% CI 0.95-1.39), or 12 months (RR 1.13, 95% CI 0.94-1.35). BUD was neither more effective than azathioprine (RR 0.81, 95% CI 0.61-1.08), nor weaning doses of prednisolone for maintenance of remission at 12 months (RR 0.79; 95% CI 0.55-1.13), but was better than mesalamine (RR 2.51, 95% CI 1.03-6.12). BUD 3 mg daily was more effective than placebo at 3 months (RR 1.31, 95% CI 1.03-1.67). This benefit was not sustained at 6 months (RR 1.10; 95% CI 0.81-1.50), or 12 months (RR 1.04, 95% CI 0.84-1.30). The use of BUD 6 mg resulted in a modest improvement in CDAI scores at 12 months (WMD -23.49; 95% CI -46.65 to -0.32). Adverse events were more frequent in patients treated with 6 mg of BUD, compared with placebo (RR 1.49; 95% CI 1.01-2.19). Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg daily (RR 2.88; 95% CI 1.72-4.82) and 3 mg daily (RR 2.73, 95% CI 1.34-5.57), compared with placebo. Patients receiving BUD were less likely to withdraw due to adverse events than those receiving azathioprine (RR 0.42; 95% CI 0.18-0.97). Conclusion: BUD is not more effective than placebo for maintenance of remission in CD. BUD results in a modest drop in CDAI scores; however, these benefits are offset by higher adverse events and more frequent adrenocorticoid suppression in patients receiving BUD. Lack of superiority of BUD compared to azathioprine is a new finding in this update. Disclosure - EK, AR, EIB - none. GGK - speaker for Merck, Schering-Plough, Abbott, and UCB Pharma; participated in advisory board meetings for Abbott, Merck, Schering-Plough, Shire, and UCB Pharma; research support from Abbott and Shire. ARO - advisory board for Janssen Canada, Abbvie Canada, Nestle Canada; research support (clinical trial site) from Janssen, Abbvie, Optimer US, Janssen US, Astra-Zeneca AHS - advisory boards for Merck, Abbott, and Shire; Speakers Bureau for Merck, Abbott, Shire, Aptalis, and Warner Chilcott; research support from Merck and Abbott CHS - advisory boards for Janssen Canada, Abbvie; Speaker for Janssen Canada; research support from Janssen Canada.

Interim evaluation of our experience with infliximab treatment in IBD

Introduction: Infliximab (IFX) became an accepted treatment modality in active luminal disease and for enterocutaneous fistulae in patients suffering from Crohn's disease (CD). Aims: Retrospective evaluation of our experience with IFX treatment from three different standpoints: (1) routine (standard and maintenance) IFX treatment in CD. (2) effects of initial (step-down) IFX therapy in CD, (3) possibilities of IFX treatment in ulcerative colitis (UC). Material and methods: (1) Standard and maintenance IFX treatment was introduced in 49 CD patients with fistulae or steroid-resistent cases. Indicators were: proven closure of fistulae, and changes in Crohn's disease activity index (CDAI). (2) Initial IFX treatment – as the start of „step down“ therapy – has been applied in four freshly discovered CD patients. Indicators were: changes in CDAI, further need of complementary drugs, clinical evaluation. (3) Evidence based results of IFX treatment in steroid dependent or resistant UC patients are still contradictory. IFX standard and maintenance treatment were initiated in 7 UC patients. Indicators were: decrease in steroid need, changes in Modified Truelove-Witts severity index (MTWSI). Results: (1) Fistulae closed in 13/16 (81%) of cases. CDAI decline was significant in every case, side effects developed in 2 cases, resulting in halting IFX therapy. (2) Newborn diagnosis of severe CD may lead to hard treatment decisions. Starting with initial IFX therapy seem to support the paradigma of “step-down“ therapy, all of our four cases showed significant improvement in clinical status, CDAI decreasing, and reduced need of complementary therapy. (3) Seven UC patients with extreme therapeutic involvement (very high steroid need, insufficient response to immunesuppressive drugs) were selected for IFX treatment trial. MTWSI responses were significant in 4/7 cases, while in all others steroid dose decrease or discontinuation were possible. Discussion: Without doubt, IFX seems to be the most spectacular medicine in recent years for patients with IBD. Cost-effectiveness must be re-evaluated by state health policy.

Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity.

Our objective was to explore the relationship between psychological distress and subsequent Crohn's disease (CD) activity. Eighteen CD patients were followed prospectively for 2 years at 8- to 12-week intervals. Disease activity was assessed using the Crohn's Disease Activity Index (CDAI). Psychological distress was assessed using the following self-administered questionnaires: Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS), and multiple Holmes Recent Life Changes (RLC) Questionnaires. The effects of psychological distress on current and subsequent CDAI (approximately 8-12 weeks later) were assessed using generalized estimating equations (GEE). The mean CDAI score during follow-up was 138 +/- 86, with a median of 121 (range, 0 to 394). BDI scores (possible range of 0 to 63) were independently associated with CDAI scores simultaneously (beta = 5.64, P = 0.004) and 8-12 weeks later (beta = 6.08, P = 0.004). Higher levels of anxiety, hopelessness, and recent life changes were also suggestive of higher CDAI scores, however, their effects were generally of lesser magnitude and not independent of the influence of depressive symptoms. Levels of depressive symptoms are positively associated with future changes in CDAI. Routine psychological assessment may help to identify patients at higher risk for exacerbation.

Crohn’s disease: a two-year prospective study of the association between psychological distress and subsequent disease activity

Our objective was to explore the relationship between psychological distress and subsequent Crohn's disease (CD) activity. Eighteen CD patients were followed prospectively for 2 years at 8- to 12-week intervals. Disease activity was assessed using the Crohn's Disease Activity Index (CDAI). Psychological distress was assessed using the following self-administered questionnaires: Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS), and multiple Holmes Recent Life Changes (RLC) Questionnaires. The effects of psychological distress on current and subsequent CDAI (approximately 8–12 weeks later) were assessed using generalized estimating equations (GEE). The mean CDAI score during follow-up was 138 ± 86, with a median of 121 (range, 0 to 394). BDI scores (possible range of 0 to 63) were independently associated with CDAI scores simultaneously (β =5.64, P=0.004) and 8–12 weeks later (β =6.08, P=0.004). Higher levels of anxiety, hopelessness, and recent life changes were also suggestive of higher CDAI scores, however, their effects were generally of lesser magnitude and not independent of the influence of depressive symptoms. Levels of depressive symptoms are positively associated with future changes in CDAI. Routine psychological assessment may help to identify patients at higher risk for exacerbation.

Pediatric Crohn Disease Activity Index: Responsive to Short‐term Change

ABSTRACTBackground/AimsDespite documented feasibility, reliability, and validity, the Pediatric Crohn's Disease Activity Index (PCDAI) has yet to be demonstrated to be sensitive to change in the time frame of acute treatment trials. We evaluated short‐term responsiveness and determined the minimal change in PCDAI score associated with a clinically meaningful improvement in disease activity.MethodsStandardized effect size (SES) and standardized response mean (SRM) were calculated as measures of responsiveness among pediatric patients being treated for acute exacerbations of Crohn disease 1) in a regular clinical practice setting and 2) as part of a multicenter, randomized controlled trial (RCT). Receiver operating characteristic (ROC) curves were constructed to determine the minimal PCDAI score change associated with significant clinical improvement used as the gold standard in 1) physician global assessment of change and in 2) change in adult Crohn disease activity index (CDAI).ResultsAmong responders, the SES and SRM of the PCDAI were 1.78 and 1.41 (95% CI: 0.89–1.92) and 2.10 and 1.95 (95% CI: 1.70–2.20) in the clinical practice setting and RCT setting, respectively. The optimal minimal PCDAI change score associated with clinically significant change in physician global assessment was determined to be ‐12.5 (sensitivity 83.3%, specificity 92.3%). In the RCT setting a change in PCDAI of –10 corresponded to a change in CDAI of ≱ 70 points.ConclusionsThe PCDAI is responsive to improvement in disease activity in Crohn disease patients over a short interval. As such, the PCDAI is an appropriate instrument to use in pediatric acute treatment trials.

ANCA Pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in crohn's disease

In the clinical trial, a lower response to infliximab was observed in some patients after multiple infusions, suggesting that clinical subgroups of Crohn's disease (CD) exist based on response to anti-tumor necrosis factor (anti-TNF). The aim of this study was to characterize these subgroups further by antineutrophil cytoplasmic antibody (ANCA) pattern and TNF genotype. Crohn's Disease Activity Index (CDAI) data from the North American patients in the clinical trial (n = 59) were evaluated as the response parameter. Speckled ANCA (sANCA) subjects were ANCA positive by ELISA with a speckling over the entire neutrophil on indirect immunofluorescence. Genotypes were determined for polymorphisms in the TNF/lymphotoxin alpha (LTA) region. Response to infliximab as median change in CDAI was placebo (least response) < perinuclear ANCA (pANCA) < not pANCA or sANCA < sANCA (greatest response) (P(overall) = 0.003; 4 weeks). The response of subjects with sANCA was significantly different from that of placebo at all time points; that of pANCA subjects was not. Homozygotes for the LTA NcoI-TNFc-aa13L-aa26 haplotype 1-1-1-1 did not respond (P(overall) = 0.007). These observations suggest that sANCA may identify a CD subgroup with a better response to infliximab and that pANCA and homozygosity for the LTA 1-1-1-1 haplotype may identify subgroups with a poorer response.