A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to Infliximab in Crohn’s Disease

BackgroundInfliximab is effective in inducing and maintaining remission in patients with Crohn’s disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD.MethodsFrom January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study. Serum samples were collected at baseline and week 2 of infliximab treatment. Serum levels of 35 cytokines were assessed in 18 patients from the discovery cohort and were further evaluated in the 60-patient cohort 1. Then, candidate cytokines and other serological biomarkers were used to construct a predictive model by logistic regression in a 182-patient cohort 2. PNR was defined based on the change of CD activity index or clinical symptoms.ResultsAmong the 35 cytokines, matrix metalloproteinase 3(MMP3) and C-C motif ligand 2 (CCL2) were two effective serum biomarkers associated with PNR in both the discovery cohort and cohort 1. In cohort 2, serum level of MMP3, CCL2 and C-reactive protein (CRP) at 2 weeks after infliximab injection were independent predictors of PNR, with odds ratios (95% confidence interval) of 1.108(1.059-1.159), 0.940(0.920-0.965) and 1.102(1.031-1.117), respectively. A PNR classifier combining these three indicators had a large area under the curve [0.896(95% CI:0.895-0.897)] and negative predictive value [0.918(95%CI:0.917-0.919)] to predict PNR to infliximab.ConclusionsMMP3, CCL2, and CRP are promising biomarkers in prediction of PNR to infliximab, and PNR classifier could accurately predict PNR and may be useful in clinical practice for therapy selection.

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Impact of extracum of curcuma longa in a composition of rectal suppositoria on of lipid peroxidal oxidation indications in the thick intestiness in experimental Crohn’s disease

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-175-3-80-86 ◽

2020 ◽

pp. 80-86

Author(s):

M. V. Osikov ◽

E. V. Simonyan ◽

A. E. Bakeeva

Keyword(s):

Lipid Peroxidation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Large Intestine ◽

Clinical Symptoms ◽

Activity Index ◽

Clinical Activity ◽

Lipid Peroxidation Products ◽

Turmeric Extract ◽

Rectal Suppositories

The aim. To conduct a comparative analysis of the effect of turmeric extract and 5-aminosalicylic acid (5-ASA) in the composition of rectal suppositories in clinical symptoms and the content of lipid peroxidation products in the mucous membrane of the large intestine in experimental Crohn’s disease (CD).Materials and methods. The experiment was performed on 70 non-linear white Wistar rats. CD was modeled by rectal administration of trinitrobenzenesulfonic acid, rectal suppositories were used each 12 hours: with 5-ASA in a dose of 50 mg, with 10% turmeric extract of original composition, weighing 0.3 g each. On the 3rd, 5th and 7th day of CD, the clinical status was determined by the modified Disease activity index scale and the content of lipid peroxidation products in the large intestine mucosa.Results. In the dynamics of CD in the colon, the content of primary, secondary and final lipid peroxidative products in the heptane and isopropanol phases increases; the severity of clinical signs (weight loss, diarrhea, blood in the fecal masses) increases with increasing content of POL. The use of rectal suppositories with turmeric extract in case of CD reduces the severity of clinical symptoms, reduces the content of lipid peroxidation products mainly in the isopropanol phase of the colon lipid extract; an association was established between the index of clinical activity of CD and the content of lipid peroxidation products in the large intestine. The effectiveness of local application of turmeric extract in the composition of rectal suppositories is comparison with the effectiveness of the use of rectal suppositories with 5-ASA in terms of the clinical activity index and the content of lipid peroxidation products in the large intestine.

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Exclusive Enteral Nutrition versus Infliximab in Inducing Therapy of Pediatric Crohn’s Disease

Gastroenterology Research and Practice ◽

10.1155/2017/6595048 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Youyou Luo ◽

Jindan Yu ◽

Jingan Lou ◽

Youhong Fang ◽

Jie Chen

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Effects ◽

Enteral Nutrition ◽

Clinical Symptoms ◽

Activity Index ◽

Group Versus ◽

Disease Activity Index ◽

Mucosal Healing ◽

Exclusive Enteral Nutrition

Aim. To compare the effectiveness of exclusive enteral nutrition (EEN) and infliximab (IFX) therapy in pediatric Crohn’s disease (CD). Methods. In a prospective study of children initiating EEN or infliximab therapy for CD, we compared clinical outcomes using the pediatric Crohn’s disease activity index (PCDAI), growth improvement, endoscopic mucosal healing, and adverse effects. Data were measured at baseline and after 8 weeks of therapy. Results. We enrolled 26 children with CD; of whom, 13 were treated with infliximab, 13 with EEN. Clinical response (PCDAI) reduction ≥ 15 or final PCDAI ≤ 10 was achieved by 83.3% in the EEN group and 90.9% in the IFX group. Body mass index for age (BMIFA) z-scores were significantly increased in both groups (P<0.05). No significant differences were observed in PCDAI, height for age (HFA), or BMI recovery between two groups. Adverse effects were detected in 30.7% on infliximab and 0% on EEN. Mucosal healing was achieved in 71.4% cases in the EEN group versus 85.7% in the IFX group. Conclusion. EEN provided similar improvements as IFX in clinical symptoms, mucosal healing, and BMI. EEN therapy has less adverse effects when compared with IFX. This trial is registered with the Clinical Registration Number: ChiCTR-OON-17010834.

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Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

Gastroenterology Research and Practice ◽

10.1155/2015/850351 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Cem Çekiç ◽

Adnan Kırcı ◽

Sezgin Vatansever ◽

Fatih Aslan ◽

Huriye Erbak Yılmaz ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Normal Population ◽

Disease Activity Index ◽

Serum Levels ◽

Control Group ◽

Serum Samples ◽

Reactive Protein

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn’s disease (CD).Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn’s disease activity index (CDAI).Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL)p=0.03. SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL)p<0.001. A significant positive correlation was found between SDC-1 and CRP (r=0.687,p<0.001) and between SDC-1 and CDAI (r=0.747,p<0.001).Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.

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The role of pelvic MRI in assessment of combined surgical and Infliximab treatment for perianal Crohn's disease

Acta chirurgica iugoslavica ◽

10.2298/aci1003089g ◽

2010 ◽

Vol 57 (3) ◽

pp. 89-95 ◽

Cited By ~ 6

Author(s):

V. Gligorijevic ◽

N. Spasic ◽

D. Bojic ◽

M. Protic ◽

P. Svorcan ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Activity Index ◽

Fistula Tract ◽

Infliximab Treatment ◽

Adequate Treatment ◽

Pelvic Mri ◽

Perianal Crohn’S Disease ◽

Perianal Crohn's Disease

AIM: To evaluate the role of pelvic MRI in diagnosis and assesment of combined surgical and infliximab treatment of perianal Crohn's disease (PACD). METHOD: 24 patients with signs of PACD were prospectively evaluated. They were previously treated with azathyoprin for a period of 6 months to 7 years and antibiotics and than started on Infliximab 5 mg/kg (IFX) at 0,2 and 6 weeks induction protocol. Luminal CD activity was assesed by colonoscopy. Perianal Disease Activity Index (PDAI) was calculated to evaluate perianal fistulae activity. Surgical examination under anesthesia (EUA) was performed and noncutting seton placed where appropriate. Pelvic MRI was performed in each patient before Infliximab treatment, and in half of the patients after IFX. MRI criteria were used to asses activity and remission of PACD. RESULTS: 14/24(58.5%) patients had ileocolitis, 10/24 (41.5%) colitis, and in 22/24(91.7%) rectum was affected. Median disease duration was 5.5+2.5 years. MRI revealed simple fistula in 4/24 (16.7%) and complex fistula in 20/24 (83.3%) patients. Abscess was present in 19/24(79%) patients. Enterocutaneous and recto-vaginal fistula was found in 2(8.3%) and 3(12.5%) patients, respectively. Median PDAI before and 8 weeks after IFX treatment was 8.3+2.08 and 3.5+1.03, respectively (p=0.00064). Incomplete response (reduction fistulae drainage by 50%) was found in 10/24(42%) patients, complete response (no drainage) in 11/24 (46%) patients, while in 3/24(12.5%) new fistula opened. Control pelvic MRI was performed in 13/24 (54%) patients. Of those, 9/13(69%) had complete remission according to MRI criteria. Seton was removed after second IFX dose in 15/24 (62.5%) patients and placed again in 2/24 (8%) patients 4 months after completion of IFX treatment. CONCLUSION: In patients with PACD, pelvic MRI before and after IFX treatment is an important diagnostic tool to asses fistula tract localization, reveal abscess, planning adequate treatment approach and assess the effect of treatment. Surgical decision to remove seton was in accordance with MRI criteria for remission in PACD.

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Dynamics of lipid peroxidation in the large intestine during experimental Crohn's disease and the use of rectal suppositories with long turmeric extract

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2020.03.131-136 ◽

2020 ◽

pp. 131-136

Author(s):

М.В. Осиков ◽

Е.В. Симонян ◽

А.Е. Бакеева ◽

О.И. Огнева

Keyword(s):

Lipid Peroxidation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Large Intestine ◽

Clinical Symptoms ◽

Activity Index ◽

Disease Activity Index ◽

Turmeric Extract ◽

Rectal Suppositories

Цель исследования - проведение сравнительного анализа влияния экстракта куркумы длинной и 5-аминосалициловой кислоты (5-АСК) в составе ректальных суппозиториев на клиническую картину и содержание продуктов перекисного окисления липидов (ПОЛ) в слизистой оболочке толстого кишечника при экспериментальной болезни Крона (БК). Методика. Эксперимент выполнен на 70 белых крысах-самцах Wistar. БК моделировали ректальным введением тринитробензосульфоновой кислоты. Ректальные суппозитории (массой 0,3 г каждая) начинали применять через 12 ч. Содержание 5-АСК в суппозиториях составляло 50 мг, 10% экстракта куркумы длинной оригинального состава 0,000075 г. На 3-и, 5-е и 7-е сут после моделирования БК оценивали клинический статус по модифицированной шкале Disease activity index и содержание продуктов ПОЛ в слизистой оболочке толстого кишечника. Результаты. В динамике БК в толстом кишечнике увеличивается содержание первичных, вторичных и конечных продуктов ПОЛ в гептановой и изопропанольной фазах; тяжесть клинических признаков (снижение массы тела, диарея, кровь в каловых массах) нарастает по мере увеличения содержания продуктов ПОЛ. Применение при БК ректальных суппозиториев с экстрактом куркумы снижает выраженность клинических симптомов, уменьшает содержание продуктов ПОЛ преимущественно в изопропанольной фазе липидного экстракта толстого кишечника; установлена корреляция индекса клинической активности БК с содержанием продуктов ПОЛ в толстом кишечнике. Заключение. Эффективность локального применения экстракта куркумы в составе ректальных суппозиториев сопоставима по эффективности с применением ректальных суппозиториев с 5-АСК по показателям индекса клинической активности и по содержанию продуктов ПОЛ в слизистой толстого кишечника. Aim. To compare effects of turmeric extract and 5-aminosalicylic acid (5-ASA) formulated into rectal suppositories on clinical symptoms and content of lipid peroxidation products (LPP) in the mucous membrane of the large intestine in experimental Crohn’s disease (CD). Methods: Experiments were performed on 70 Wistar male rats. CD was modeled by rectal administration of trinitrobenzenesulfonic acid; rectal suppositories (0.3 g each) were used every 12 h. The suppositories contained 5-ASA (50 mg) or 10% turmeric extract with an original composition (0.000075 g). On days 3, 5, and 7 of CD, the clinical status was evaluated with a modified Disease Activity Index scale, and LPP concentrations were measured in the large intestine mucosa. Results. In the course of CD in the colon, concentrations of primary, secondary, and final LPP in the heptane and isopropanol phases increased; severity of clinical signs (weight loss, diarrhea, blood in fecal masses) increased with increasing LPP concentrations. The use of rectal suppositories with turmeric extract alleviated severity of clinical symptoms and reduced LPP content primarily in the isopropanol phase of colon lipid extract. The index of CD clinical activity of CD was correlated with the large intestinal LPP content. Conclusion. Effectiveness of the local application of turmeric extract formulated into rectal suppositories was comparable with that of rectal suppositories with 5-ASA as determined by the Disease Activity Index and the LPP content in the large intestine.

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P574 Exploring treatment of Crohn’s disease and ulcerative colitis in the Middle East and Northern Africa: An analysis of the HARIR observational cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.695 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S531-S532

Author(s):

W Hamed ◽

O E Salem ◽

O Alharbi ◽

M Sharaf ◽

C Taylor ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Middle East ◽

Crohn's Disease ◽

Treatment Response ◽

Activity Index ◽

Middle Eastern ◽

Limiting Factors ◽

Infliximab Treatment ◽

Western Asia

Abstract Background This analysis of the HARIR study explored disease characteristics, treatment and outcomes of patients (pts) with diseases including Crohn’s disease (CD) or ulcerative colitis (UC) treated with biologics in clinical practice where data are limited: North Africa, the Middle East and Western Asia. Methods HARIR was a prospective, observational, multicentre, cohort, phase 4 study (NCT03006198). This analysis included adult pts with CD or UC who were starting infliximab, golimumab or ustekinumab (study period: March 2016–December 2018; terminated early). Pts needed to be previously untreated with study drugs or received ≤2 biologics prior to enrolment. Treatment was at physician’s discretion. Pts were followed for 1 year or until study withdrawal (amended from 2 years); pts who stopped the study due to study termination were considered to have completed the study. For CD, the main efficacy outcomes were Crohn’s Disease Activity Index (CDAI) treatment response, remission and change from baseline of inflammatory Bowel Disease Questionnaire (IBDQ). Adverse events (AEs) and serious AEs (SAEs) were recorded. Results A total of 86 pts with CD or UD from Algeria, Egypt, Kuwait, Qatar and Saudi Arabia were enrolled; 56 pts completed the study. Target enrolment was achieved for CD but was 1 pt short for UC. Mean (SD) age was 32.7 (11.5) years for CD and 29.6 (9.4) years for UC. Most pts with CD and UC had not previously received biologics (CD: 95.2%, 59/62; UC: 66.7%, 16/24). All pts with CD and UC received infliximab. Investigators noted lack of access to study drug and concomitant treatments as limiting factors for enrolment. Immunosuppressant use was low; methotrexate was used by 1 pt with UC prior to study treatment and azathioprine or mycophenolate mofetil were used by 19.4% (12/62) of pts with CD and 24.0% (6/25) of pts with UC during the study. At Month 3, 29.2% (14/48) of pts with CD had a positive treatment response (CDAI score ≥70 to ≥25% versus baseline; Figure). The percentage of pts with CD in clinical remission was 53.8% (28/52) at baseline and 70.8% (34/48) at Month 3 (Figure). Mean (SD) IBDQ score increased by 11.3 (39.6%) points from baseline to Month 3 (Figure). Overall, pt numbers were too low to analyse outcomes for CD after Month 3 and over the study duration for UC. In CD and UC, respectively, AEs were reported by 25.8% (16/62) and 37.5% (9/24) of pts and SAEs were reported by 12.9% (8/62) and 16.7% (4/24) of pts. Conclusion Infliximab treatment was well tolerated, and a moderate clinical response was observed for this Middle Eastern and Northern African population. Limited accessibility to biologics and concomitant treatments in these countries restricted conduct of the study.

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Adalimumab Dose-Escalation Therapy Is Effective in Refractory Crohn’s Disease Patients with Loss of Response to Adalimumab, Especially in Cases without Previous Infliximab Treatment

Case Reports in Gastroenterology ◽

10.1159/000496453 ◽

2019 ◽

Vol 13 (1) ◽

pp. 37-49

Author(s):

Taketo Suzuki ◽

Tsutomu Mizoshita ◽

Tomoya Sugiyama ◽

Yoshikazu Hirata ◽

Yoshihide Kimura ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Dose Escalation ◽

Activity Index ◽

Disease Activity Index ◽

Infliximab Treatment ◽

C Reactive Protein ◽

Protein Levels ◽

Reactive Protein ◽

Loss Of Response

Background/Aims: Adalimumab dose escalation is one of the most important options in refractory Crohn’s disease patients with loss of response to adalimumab. The goal of this study was to evaluate the effectiveness of adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab, since there are few reports of adalimumab dose escalation, especially in East Asia. Methods: The clinical response to adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab was evaluated retrospectively, using the Crohn’s disease activity index score, serum C-reactive protein levels, and endoscopic analyses. Results: Of the 203 Crohn’s disease patients treated with anti-tumor necrosis factor, 14 refractory Crohn’s disease patients with loss of response to adalimumab received adalimumab dose-escalation therapy. The C-reactive protein level was significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in the whole group, although there were no significant reductions of Crohn’s disease activity index scores. Both Crohn’s disease activity index scores and C-reactive protein levels were significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in patients without previous infliximab treatment, although C-reactive protein levels were positive in all cases with previous infliximab exposure at weeks 12 and 52. Endoscopic mucosal healing was achieved with adalimumab dose escalation in 2 cases without previous infliximab treatment. Conclusions: Adalimumab dose-escalation therapy is effective in refractory Crohn’s disease patients with loss of response to adalimumab, especially in cases without previous infliximab treatment.

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The Periodontopathic Pathogen, Porphyromonas gingivalis, Involves a Gut Inflammatory Response and Exacerbates Inflammatory Bowel Disease

Pathogens ◽

10.3390/pathogens11010084 ◽

2022 ◽

Vol 11 (1) ◽

pp. 84

Author(s):

Yu-Chen Lee ◽

Chih-Yi Liu ◽

Chia-Long Lee ◽

Ruo-Han Zhang ◽

Chi-Jung Huang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Porphyromonas Gingivalis ◽

Bowel Disease ◽

Clinical Symptoms ◽

Activity Index ◽

Taxonomic Assignment ◽

Simultaneous Treatment ◽

Inflammatory Bowel

Periodontal disease (PD) is one of the most prevalent disorders globally and is strongly associated with many other diseases. Inflammatory bowel disease (IBD), an inflammatory condition of the colon and the small intestine, is reported to be associated with PD through undetermined mechanisms. We analyzed taxonomic assignment files from the Crohn’s Disease Viral and Microbial Metagenome Project (PRJEB3206). The abundance of Porphyromonadaceae in fecal samples was significantly different between patients with Crohn’s disease and control volunteers. Dextran sulfate sodium was used to induce colitis in mice to reveal the effect of this periodontopathic pathogen in vivo. After intrarectal implantation of Porphyromonas gingivalis (Pg)—the primary pathogen causing PD—the disease activity index score, colonic epithelial loss, and inflammatory cell infiltration were intensified. In addition, tumor necrosis factor-α and interleukin-6 showed the highest levels in Pg-infected colons. This revealed the importance of Pg in the exacerbation of IBD. Thus, simultaneous treatment of PD should be considered for people with IBD. Moreover, implantation of Pg in the rectum worsened the clinical symptoms of colitis in mice. Because Pg participates in the pathogenesis of IBD, reducing the chances of it entering the intestine might prevent the worsening of this disorder.

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Transabdominal bowel sonography modifications in patients with active Crohn's disease before and after infliximab treatment

Gastroenterology ◽

10.1016/s0016-5085(01)81353-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A273-A273

Author(s):

C SERRA ◽

P GIONCHETTI ◽

L VOLPE ◽

C MORELLI ◽

M CAMPIERI ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Infliximab Treatment ◽

Before And After ◽

Bowel Sonography

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Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease

Molecules ◽

10.3390/molecules24030449 ◽

2019 ◽

Vol 24 (3) ◽

pp. 449 ◽

Cited By ~ 12

Author(s):

Yunjia Lai ◽

Jingchuan Xue ◽

Chih-Wei Liu ◽

Bei Gao ◽

Liang Chi ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

High Resolution Mass Spectrometry ◽

Signaling Cascades ◽

Compound Identification ◽

Serum Samples ◽

Therapy Assessment ◽

Integral Role ◽

Important Pathway ◽

Biomarker Research

: Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.

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