Clinical Activity Of Ulcerative Colitis Research Articles

Correlation between the Quantity and Type of Dietary Fiber with the Activity in Mexican Patients with Ulcerative Colitis (UC).

Background/Objective: Ingestion of dietary fiber can influence in the remission of patients with ulcerative colitis (UC). There are no current recommendations for fiber intake in UC; therefore, we evaluate the association between dietary fiber and the activity of the disease. Methods: Ours is a cross-sectional study in patients with a confirmed diagnosis of UC to whom a 24 h recall was applied; this allowed for the estimation and classification of type of dietary fiber. The patients were divided into two groups: (1) remission and (2) active UC. We analyzed the quantity and type of fiber with the grades of disease activity through Spearman correlation and logistic regression. Results: A total of 152 patients were included; it was found that those with clinically active UC consumed less total fiber (p = 0.016) and insoluble fiber (p = 0.018). Meanwhile, in endoscopic grade, the difference was for insoluble fiber (p = 0.038). Insoluble fiber had an inversely significant correlation with fecal calprotectin levels (r = -0.204; p = 0.018). Logistic regression showed that less than 11 g of insoluble fiber was a risk factor for clinical activity (OR = 2.37; 95% CI 1.107-5.019; p = 0.026). Conclusions: Consumption below the current recommendation of total and insoluble dietary fiber is associated with clinical activity of UC.

Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis

Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease. We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n= 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data. During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1× 10-4) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model. Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.

Association Between Food Specific IgG Antibodies with Clinical Activity in Patients with Inflammatory Bowel Disease: A Cross-Sectional Study

<i>Background and aim:</i> Inflammatory Bowel Disease (IBD) is an autoimmune disease that is influenced by food, an important factor in accelerating its clinical disease activity because of intestinal inflammation trough formation of antigen-antibody complex. Food-specific IgG examination can identify the types of person foods consumes that are maybe responsible for disease activity. It is useful in treating IBD without risking malnourishment as it is tailored to the individual immune profile. <i>Methods</i>: This is a cross-sectional study involving 113 patients diagnosed with IBD by colonoscopy. Examination of serum IgG specific for 220 types of foods was performed using ELISA and immuno-array techniques. Disease clinical activity was assessed using the Mayo Index and Crohn Disease Activity Index. <i>Results:</i> The highest proportion of dietary IgG in Chron’s disease was peas (100%), barley (97.9%), eggs (95.9%), milk (81.6%), and corn (75.5%); while in ulcerative colitis it was barley (98.4%), peas (96.8%), egg whites (92.2%), corn (82.8%), and prunes (78.1%). In ulcerative colitis, there was a weak negative correlation between cashew nuts IgG (r = -0.347, p=0.041) and chickpeas IgG (r =-0.473, p=0.017) with clinical disease activity; while in Chron’s disease, a weak positive correlation with disease activity was seen in barley (r = 0.261, p = 0.042). <i>Conclusion:</i> There was a weak negative correlation between cashew and chickpea-specific IgG antibodies with clinical activity of ulcerative colitis, and a weak positive correlation between barley-specific IgG antibodies and Chron’s disease clinical activity.

Association between Food Specific IgG Antibodies with Clinical Activity of Disease in Patients with Inflammatory Bowel Disease: A Cross-Sectional Study

Background: Inflammatory bowel disease (IBD) is an autoimmune disease that is influenced by food, an important factor in accelerating its clinical disease activity because of intestinal inflammation trough formation of antigen-antibody complex. Food-specific IgG examination can identify the types of person foods consumes that are maybe responsible for disease activity. It is useful in treating IBD without risking malnourishment as it is tailored to the individual immune profile.Method: This is a cross-sectional study involving 113 patients diagnosed with IBD by colonoscopy. Examination of serum IgG specific for 220 types of foods was performed using ELISA and immuno-array techniques. Disease clinical activity was assessed using the Mayo index and Crohn's disease activity index.Results: The highest proportion of dietary IgG in Crohn's disease was peas (100%), barley (97.9%), eggs (95.9%), milk (81.6%), and corn (75.5%); while in ulcerative colitis it was barley (98.4%), peas (96.8%), egg whites (92.2%), corn (82.8%), and prunes (78.1%). In ulcerative colitis, there was a weak negative correlation between cashew nuts IgG (r = -0.347; p = 0.041) and chickpeas IgG (r = -0.473; p = 0.017) with clinical disease activity; while in Crohn's disease, a weak positive correlation with disease activity was seen in barley (r = 0.261; p = 0.042).Conclusion: There was a weak negative correlation between cashew and chickpea-specific IgG antibodies with clinical activity of ulcerative colitis, and a weak positive correlation between barley-specific IgG antibodies and Crohn's disease clinical activity.

Combined effects of granulocyte and monocyte adsorption apheresis and corticosteroids on ulcerative colitis.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Predictive value of faecal calprotectin in ulcerative colitis – single centre experience

Objectives Faecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. The aim of this study was to establish the value of faecal calprotectin concentration as a predictor of remission in ulcerative colitis and its correlation with laboratory, endoscopic and clinical findings. Methods The single centre study included 126 adult patients with established diagnosis of ulcerative colitis consecutively visiting our Day clinic from March 2017 to March 2019. We measured serum biomarkers- CRP, haemoglobin, leukocytes and platelets. Faecal calprotectin was determined from stool, and endoscopy was performed with calculation of MAYO endoscopic subscore system (MES 0–1: remission, and MES 2–3: active disease). Clinical assessment was done by using Mayo score for ulcerative colitis (clinical Mayo score <2:remission, >5: active disease).The statistical analysis was performed using an univariate and multivariate model of disease remission prediction using logistic regression. Results According to univariate analysis the increase of faecal calprotectin concentration by 10 ug/g is associated with an 8% decrease in probability of disease remission (OR 0.9921, p < .05). In the multivariate analysis, faecal calprotectin remained a significant predictor of disease remission (OR 0.9948, 95% CI 0.9914–0.9982, p = .0028), however, with a significant contribution of C-reactive protein (OR 0.8340, 95% CI 0.7085–0.9818, p = .0292). According to our model the cut off value for faecal calprotectin was 154 ug/g. Conclusion Our results have shown that faecal calprotectin is an independent predictor of remission in UC patients. The results of our study represent real-life data from a single university centre dealing with FC as a prognostic marker in patients with UC. KEY MESSAGES Faecal calprotectin is an independent predictor of remission in UC patients. Recent studies have suggested that calprotectin correlates well with endoscopic activity of inflammation but correlation of faecal calprotectin in a phase of remission hasn’t been evaluated yet. We have found that other inflammatory biomarkers do not correlate well with either endoscopic or clinical activity in ulcerative colitis.

Связь биомаркеров воспаления в толстой кишке с индексами активности неспецифического язвенного колита

Цель: проанализировать содержание маркеров кишечного воспаления в крови и кале больных с неспецифическим язвенным колитом (НЯК) в сопоставлении с известными индексами активности болезни. Материалы и методы. Исследованы 60 пациентов с подтвержденным диагнозом НЯК. Клиническую активность НЯК оценивали с помощью клинического индекса активности по D. Rachmilewitz. Эндоскопическая активность НЯК определялась по индексу Mayo. Степень активности НЯК оценивали по комбинированному индексу Mayo. В сыворотке крови определяли содержание α-1-антитрипсина и С-реактивного белка. В кале исследовали содержание миелопероксидазы, кальпротектина и α-1-антитрипсина. Корреляционный анализ осуществляли с расчетом коэффициента корреляции Спирмена и его значимости. Результаты. У больных НЯК выявлено существенное повышение уровня фекальной миелопероксидазы в 4,5 раза (р = 0,027) и α-1-антитрипсина в кале в 3,6 раза (р = 0,039) по мере увеличения клинической активности НЯК. При выраженной степени эндоскопической активности НЯК отмечено достоверное увеличение уровня маркеров воспаления в кале: α-1-антитрипсина — в 17,8 раза (р = 0,037), кальпротектина — в 1,7 раза (р = 0,023), миелопероксидазы — 4,3 раза (р = 0,019). В то же время уровни С-реактивного белка и α-1-антитрипсина в крови не имели значимых различий в зависимости от степени активности НЯК. Выводы. У пациентов с НЯК установлены взаимосвязи уровня миелопероксидазы и кальпротектина в кале с индексом эндоскопической активности (r = 0,63, p = 0,0008 и r = 0,53, p = 0,001 соответственно), а также уровня фекальной миелопероксидазы со степенью активности заболевания согласно комбинированному индексу Mayo (r = 0,68, p = 0,0001).

Диагностическое значение числа тромбоцитов и тромбоцитарных индексов в оценке активности воспалительных заболеваний кишечника у детей

Objective. To analyze the connection between the complex of platelet indices in complete blood count test with the clinical and endoscopic activity scores for Crohn's disease (CD) and ulcerative colitis (UC) in pediatric patients and to determine their most informative threshold values. Patients and methods. In this study, 370 children aged 5 to 18 years with diagnosed CD (n = 150) and UC (n = 220) were examined. The clinical activity of UC was assessed according to PUCAI, CD – according to PCDAI; the assessment of endoscopic activity in children with UC was carried out according to UCEIS and CD – according to SES-CD. The study included platelet indices of 630 complete blood count tests (270 in patients with CD and 360 in patients with UC): platelet count (PLT), mean platelet volume (MPV), platelet large cell ratio (P-LCR) and platelet distribution width (PDW). Results. Increased platelet count and decreased platelet indices were noted as the clinical and endoscopic activity of CD and UC in children increased. A positive correlation between the clinical and endoscopic activity indices in inflammatory bowel diseases and platelet count and negative correlations with platelet indices were revealed. ROC analysis showed that the informative value of platelet indices in assessing the endoscopic activity of CD and UC is higher than in assessing the clinical activity. The optimal threshold values for platelet count (cut-off) for determining the endoscopic activity of CD and UC were 340 × 109/L and 350 × 109/L (Se 77%, Sp 69% and Se 63%, Sp 67%, respectively). The specificity of determing the endoscopic activity of 99% was obtained for platelet count of 459 × 109/L and 390 × 109/L for CD and UC, respectively. In children with CD, the indicators MPV &lt;7.8 fL, PDW &lt;7.25 fL, P-LCR &lt;15.2% characterized the presence of endoscopic disease activity with 99% specificity; in children with UC, the specificity of determining the endoscopic activity of 99% was obtained for MPV &lt;9.25 fL, PDW &lt;9.85 fL, P-LCR &lt;17.5%. Conclusion. An increase in platelet count and a decrease in platelet indices (MPV, PDW and P-LCR) can be surrogate markers of endoscopic activity of these diseases. The established threshold values will improve the accuracy of diagnosing the activity of inflammatory bowel diseases in children. Key words: Crohn's disease, ulcerative colitis, platelets, platelet indices, clinical activity, endoscopic activity

P168 BACTEROIDETES SPECIES ARE USEFUL BIOMARKER OF CLINICAL ACTIVITY IN ULCERATIVE COLITIS

Abstract Background We previously reported that there were 13 species of Bacteroidetes phylum with significantly higher or lower relative abundance in patients with ulcerative colitis (UC) than healthy individuals. In this study, we investigated the correlation between Bacteroidetes species components in fecal samples and clinical evaluations of UC. Method This study included participants above 20 years of age. Fecal samples were collected for microbial analysis from 54 patients who had active UC based on a Lichtiger’s clinical activity index (CAI) ≥ 4 or an endoscopic Mayo clinic score ≥1. DNA was extracted from the fecal samples and analyzed by next-generation sequencing (the Illumina MiSeq sequencing system) targeting hsp60. We verified associations between Bacteroidetes species and eMayo sum score (total of endoscopic Mayo clinic scores in each intestine: periphery of appendix vermiformis, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), Robarts Histopathology Index (RHI), and CAI. Results Bacteroides uniformis (R = -0.44, p = 0.002) and four others significantly correlated with eMayo sum score. Alistipes shahii (R = -0.35, p = 0.02) and three others significantly correlated with RHI. Bacteroides rodentium (R = -0.37, p = 0.006) and two others significantly correlated with CAI. Furthermore, three Bacteroidetes species (Bacteroides stercoris, Bacteroides uniformis, and Parabacteroides merdae) correlated with two of three clinical evaluations, and the total relative abundance of these three species showed stronger correlation with eMayo sum score (R = -0.52, p = 0.00007). Conclusion All eight Bacteroidetes species identified in this study represented negative correlation with the clinical activity, so these species are suggested to be lost by exacerbation. Bacteroidetes species, especially total relative abundance of three Bacteroidetes species (Bacteroides stercoris, Bacteroides uniformis, and Parabacteroides merdae) may become a biomarker for evaluating the clinical activity of UC.

P187 The significance of netrin-1 level in the clinical activity of ulcerative colitis, its association between TNF-α and IL-6

Abstract Background In this study, we investigated the importance of netrin-1 levels in ulcerative colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-α. Methods This study is a type of case–control study. Sixty-seven patients with UC (36 of them activation, 31 of remission) and 50 healthy controls were included in the study. UC patients; ‘Truelove Witts clinical activity index by remission (n = 31), mild activation (n = 21), moderate activation (n = 6) and severe activation (n = 9) were divided into groups. Netrin, IL-6 and TNF-α measurements in plasma samples were performed using enzyme-linked immunosorbent assay kit. Results Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-α, neutrophil, platelet (p &amp;lt; 0.05 for all). The plasma netrin-1 mean of UC with severe activation group (139.21 ± 48.09 pg/ml) was statistically significantly higher than that of the mild activation (p = 0,037), remission group (p = 0,001) and control group(p = 0,011). The plasma netrin-1 mean of UC with moderate activation group was statistically significantly higher than that of the mild activation(p = 0,045) and remission group(p = 0,004). Conclusion Our results reveal that plasma netrin-1 levels have been shown to be associated with UC activation, similar to proinflammatory cytokines such as TNF-α and IL-6, in UC.

Practical fecal calprotectin cut-off value for Japanese patients with ulcerative colitis.

AIMTo determine appropriate fecal calprotectin cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with ulcerative colitis (UC).METHODSWe performed a cross-sectional observational study of 131 Japanese patients with UC and measured fecal calprotectin levels by fluorescence enzyme immunoassay. The clinical activity of UC was assessed with the partial Mayo score (PMS). Relapse was defined as increase of PMS by 2 points or more in stool frequency or rectal bleeding subscore. The endoscopic and histologic activities of UC were evaluated in 50 patients within a 2-mo period from fecal sampling. Endoscopic activity was determined by Mayo endoscopic subscore, Rachmilewitz endoscopic index, and ulcerative colitis endoscopic index of severity. The histologic grade of inflammation was evaluated with biopsy specimens obtained from the endoscopically most severely inflamed site, according to the scheme by Matts grade and Riley’s score.RESULTSFecal calprotectin levels varied from 1-20783 μg/g. There was a significant correlation between the partial Mayo score and fecal calprotectin levels (r = 0.548, P < 0.001). In 50 patients who underwent colonoscopy with biopsy, levels were significantly correlated with the Mayo endoscopic subscore (r = 0.574, P < 0.001), Rachmilewitz endoscopic index (r = 0.628, P < 0.001), ulcerative colitis endoscopic index of severity (r = 0.613, P < 0.001), Riley’s histologic score (r = 0.400, P = 0.006), and Matts grade (r = 0.586, P < 0.001). Receiver-operating characteristic analyses identified the best cut-off value for the prediction of endoscopic remission as 288 μg/g, with an area under the curve of 0.777 or 0.823, while that for histologic remission was 123 or 125 μg/g, with an AUC of 0.881 or 0918, respectively. Of the 131 study patients, 88 patients in clinical remission were followed up 6 mo. During the follow-up period, 19 patients relapsed. The best fecal calprotectin cut-off value for predicting relapse was 175 μg/g.CONCLUSIONFecal calprotectin is a predictive biomarker for endoscopic and histologic remission in Japanese patients with UC.

The efficacy of curcuminoids in improvement of ulcerative colitis symptoms and patients’ self‐reported well‐being: A randomized double‐blind controlled trial

Curcuminoids are polyphenols with documented anti-inflammatory activity and has been shown to improve the symptoms of several inflammatory diseases. We aimed to evaluate the effectiveness of a nanoformulation of curcuminoids in the treatment of ulcerative colitis. This randomized double-blinded controlled trial was conducted on 56 patients aged 18 years or older with the final diagnosis of mild to moderate ulcerative colitis according to the Simple Clinical Colitis Activity Index (SCCAI). The patients were randomly assigned (using a computerized random sampling table) to receive curcuminoids nanomicelles (80 mg, three times daily, orally) plus mesalamine (3 g/24 hours, orally) as the treatment group and placebo plus mesalamine (3 g/24 hours, orally) as the control group for a period of four weeks. The severity of disease was assessed at baseline and at the end of the second and fourth weeks of the treatment according to the SCCAI. The score for urgency of defecation reduced significantly more in case group as compared with control group at four weeks after beginning the treatment. The patients in case group experienced better general condition than the control ones after 4 weeks of treatment. Overall, the mean SCCAI score was significantly lower in the patients received curcuminoids nanomicelles plus mesalamine as compared with the group received placebo plus mesalamine at fourth week after the treatment (1.71 ± 1.84 vs 2.68 ± 2.09, p = 0.050). Adding curcuminoids nanomicelles to routine treatment of patients with ulcerative colitis is associated with a significant improvement of symptoms, including reduced frequency of urgent defecation, improved patients' self-reported well-being and reduced clinical activity of ulcerative colitis. ClinicalTrials. "IRCT2017052634142N1".

The Relation Between Fecal Calprotectin and the Rate of Clinical Activity of Ulcerative Colitis

Abstract Background: Inflammatory bowel disease is a disorder with unknown origin in which environment, genetics, and immunity play a part. Although colonoscopy and biopsy are expensive and invasive, are used to monitoring the mucosal inflammation. Fecal calprotectin is a non-invasive test which has attracted a lot of attention. We aimed to determine the relation of fecal calprotectin and clinical activity of ulcerative colitis. Methods: This cross-sectional study took place with the confirmation of ethics committee of Mashhad University of Medical Sci- ences in 2014 - 2015. Patients with diagnosis of ulcerative colitis were included; demographic information was recorded and clinical activity of disease was evaluated. Fecal calprotectin was measured by the quantitative ELISA method and results of laboratory studies and clinical examinations were analyzed by SPSS software version 16. Level of significance was considered less than 0.05. Results: Seventy patients were studied (male = 56%, average age = 38  15). 25 patients (36.2%) were newly diagnosed. The average period of disease was 4.1 ± 5 years. 25 individuals (35.7%) had mild, 19 individuals (27.1%) had moderate, and 26 individuals (37.1%) had severe disease. Averages of fecal calprotectin in mild, moderate, and severe disease were 132  111, 119  44 and 141  78 g/ g, respectively. Averages of fecal calprotectin in mild and moderate disease (P = 0.874), in mild and severe (P = 0.925) and in moderate and severe disease (P = 0.662) were not significantly different. Conclusions: Although fecal calprotectin in severe ulcerative colitis is higher, it has no relation with disease clinical activity.

Effect of Cis-palmitoleic acid supplementation on inflammation and expression of HNF4γ, HNF4α and IL6 in patients with ulcerative colitis.

Cis-palmitoleic acid (Omega-7 fatty acid) is a monounsaturated fatty acid (MUFA) associated with anti-inflammatory process through specific protein interactions such as HNF4γ and HNF4α, these two genes are related to the immune response in ulcerative colitis (UC) they may act as a mediator of anti-inflammatory action. The aim of this study was to evaluate the effect of Cis-palmitoleic acid supplementation on inflammatory activity and the expression of genes HNF4γ, HNF4α and IL6 in the colonic mucosa of patients with active UC. A double-blind, randomized, placebo-controlled pilot study was conducted in 20 patients with UC. A dose of 720 mg/day of Cis-palmitoleic acid was orally administered during 8 weeks and Mayo Clinic score was used for the assessment of clinical activity in UC before and after treatment with Cis-palmitoleic acid and placebo. A total of 20 patients with UC were randomized to receive Cis-palmitoleic acid or placebo. Significant changes in the biochemical markers of inflammation were found in UC patients before and after treatment with Cis-palmitoleic acid vs. placebo such as total protein (P=0.02), hs-CRP (P=0.04) and ESR (P<0.05). The gene expression of HNF4γ and HNF4α were found to be increased in the Cis-palmitoleic acid group compared to placebo group (P=0.05 and P=0.07 respectively) as well as significant reduction upon IL6 expression in the Cis-palmitoleic acid group (P=0.005). Cis-palmitoleic acid as co-adjuvant therapy for 8 weeks seems to decrease the inflammatory activity through the increased expression of HNF4α and HNF4γ in patients with UC.

Midkine is up-regulated in both cancerous and inflamed bowel, reflecting lymph node metastasis in colorectal cancer and clinical activity of ulcerative colitis

Midkine is a multifunctional cytokine and growth factor displaying proinflammatory and pro-tumorigenic activity. Its association with bowel diseases has not been fully elucidated. Our purpose was to delineate midkine expression pattern by RT-qPCR in inflamed/cancerous bowel (n=208) and whole blood (n=150) in colorectal cancer (CRC), Crohn’s disease (CD), and ulcerative colitis (UC) and to evaluate midkine dynamics in early postoperative period following colorectal surgery. The expression of midkine was significantly up-regulated in stage III CRC and independently associated with lymph node metastasis. The expression of midkine in whole blood was up-regulated solely in N1 CRC. Midkine expression in cancer-free tissue (CRC) was also elevated and dependent on CRC advancement. In IBD, inflammation increased the bowel expression of midkine solely in UC, in a manner proportional to the disease clinical activity. Large and small bowel differed with respect to the expression of midkine in quiescent tissue (higher in small bowel) and to its correlation pattern with chemokines (in a large bowel) and angiogenic factors and cell cycle regulators (in a small bowel). Circulating midkine and its expression in whole blood dropped directly following colorectal surgery; however, the concentration of midkine in serum was restored on postoperative day three.Midkine is involved in bowel inflammation in UC and lymph node metastasis in CRC, rendering midkine an attractive target for their treatment. Owing to midkine elevation in early postoperative period and its overexpression in tumor-adjacent tissue, targeting midkine might be considered also as a prevention of CRC recurrence following curative tumor resection.

The relationship between the neutrophil–lymphocyte ratio and disease activity in patients with ulcerative colitis

Preliminary evidence suggests that a higher neutrophil–lymphocyte ratio (NLR) may be an indicator of active ulcerative colitis (UC). However, it is not clear whether the NLR is a useful and simple indicator of clinical activity in UC after adjusting for the other inflammatory markers. We designed a retrospective study to evaluate the role of the NLR in estimating disease severity in UC patients. The study consisted of 71 patients with UC and 140 age- and sex-matched healthy individuals (control group). The NLR, erythrocyte sedimentation rate, C-reactive protein, and white blood cell count were measured. The NLR values of the active UC group were elevated compared with those of the patients with inactive UC and the controls (2.59 ± 1.47, 2.03 ± 1.07, and 1.98 ± 0.85, respectively; p = 0.005). The receiver operating characteristic revealed that the optimum NLR cut-off point for active UC was 2.39. A multivariable logistic analysis showed that of the parameters studied, C-reactive protein was the only parameter able to significantly discriminate active from inactive UC (B: 0.222; p = 0.017; odds ratio: 1.248; 95% confidence interval: 1.041–1.497).

Su1242 Serum Reg Iα Is a Marker to Predict Histological and Clinical Activity in Ulcerative Colitis

Su1242 Serum Reg Iα Is a Marker to Predict Histological and Clinical Activity in Ulcerative Colitis

Long-Term Alteration of Intestinal Microbiota in Patients with Ulcerative Colitis by Antibiotic Combination Therapy

Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy.

P237 Correlation between fecal calprotectin levels and clinical activity in ulcerative colitis in a phase I study with an anti-MAdCAM-1 monoclonal antibody

P237 Correlation between fecal calprotectin levels and clinical activity in ulcerative colitis in a phase I study with an anti-MAdCAM-1 monoclonal antibody

Target Mediated Disposition (TMD) Model Based Dose Selection for Fixed SC Doses of Anti-MAdCAM-1 Monoclonal Antibody (PF-00547659) in Crohnʼs Disease

Purpose: In inflammatory bowel disease (IBD), there is still a large unmet medical need despite the introduction of anti-TNFs and new mechanisms of action are needed particularly for patients who have failed other treatments. PF-00547659 is a fully human IgG2κ anti-human MAdCAM monoclonal antibody that binds to recombinant human MAdCAM to reduce lymphocyte homing to the gut and GI inflammation. Based upon the encouraging results of a phase IIa and pharmacokinetic (PK) study in ulcerative colitis (UC) (Vermiere S, Gut 2011), a large phase 2b study in Crohn's Disease (CD) was initiated. The PK properties of PF-00547659 are typical of those displayed by IgG2 monoclonal antibodies with target-mediated disposition exhibiting dose-dependent clearance and good SC bioavailability. The dose selection strategy for this CD study which desired fixed SC doses was based upon TMD Modeling in UC (Martin SW DDW 2009 W1042). Methods: The PK data from the UC study covering a wide range of IV and SC administered doses (0.01-10 mg/kg) provided sufficient information for mechanistic characterization of an antibody exhibiting nonlinear kinetics with high affinity for MAdCAM. The TMD model was used for simulation of 8 levels of fixed doses from 7.5 mg to 225 mg. The primary criteria for optimal doses was target suppression over 12 weeks. 500 monte-carlo simulations were performed including inter-subject and intra-subject variability. Results: Monthly SC doses of 75 mg provide greater than 95% target suppression over 12 weeks in 90% of subjects. Two additional doses of one half-log below (22.5 mg) and above (225 mg) were selected to provide information regarding the minimal and maximum effective suppression level necessary for efficacy in CD. The selected dose range has good separation in PK exposure, is within the range that was well tolerated and exhibited signs of clinical activity in UC (Figure).Figure: No Caption available.Conclusion: Based upon the simulation results, PF-00547659 SC monthly doses of 22.5 mg, 75 mg and 225 mg were selected for the phase 2b CD study. Doses above 22.5 mg SC inhibits > 90% of MAdCAM activity with the CI narrowing with increasing doses up to 225 mg SC which inhibits 99.8% of MAd-CAM activity. Disclosure: William Sandborn - Consultant Pfizer, Jason WIlliams - Pfizer Employee, Fabio Cataldi - Pfizer Employee, Gail Comer - Pfizer Employee. This research was supported by an industry grant from Pfizer.