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Wang W, Cao W, Zhang S, Chen D, Liu L. The Role of Calprotectin in the Diagnosis and Treatment of Inflammatory Bowel Disease. Int J Mol Sci 2025; 26:1996. [PMID: 40076618 PMCID: PMC11900593 DOI: 10.3390/ijms26051996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/21/2025] [Accepted: 02/23/2025] [Indexed: 03/14/2025] Open
Abstract
The management of inflammatory bowel disease (IBD), which is characterized by immunodeficiency, has attracted increasing attention, highlighting the necessity for more precise and streamlined diagnostic approaches in clinics. Calprotectin, an immune cell-derived protein with inherent anti-inflammatory and antimicrobial properties, plays a pivotal role in immune regulation and intestinal homeostasis. Its expression levels are intricately linked to IBD activity, enabling differentiation between inflammatory and non-inflammatory states while predicting recurrence risks. As a non-invasive biomarker, fecal calprotectin (FC) and serum calprotectin (SC) analysis offers high reproducibility and clinical utility, facilitating both IBD diagnosis and real-time disease monitoring. Beyond its diagnostic specificity in distinguishing IBD from other gastrointestinal disorders, calprotectin also emerges as a promising therapeutic target, due to its dual role in modulating inflammatory pathways and interacting with the gut microbiota. With collaborative advancements in standardized detection protocols and innovative research methodologies, it is anticipated that calprotectin-based strategies will be integrated into mainstream clinical practice for IBD.
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Affiliation(s)
- Wenqian Wang
- Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian 116044, China (S.Z.)
| | - Wenfu Cao
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian 116044, China (S.Z.)
| | - Shenyun Zhang
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian 116044, China (S.Z.)
| | - Dapeng Chen
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian 116044, China (S.Z.)
| | - Lihong Liu
- Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
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Kardas Yildiz A, Urganci N, Usta AM. Evaluation of fecal neutrophil gelatinase-associated lipocalin levels in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2025. [PMID: 39968866 DOI: 10.1002/jpn3.70015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/26/2024] [Accepted: 01/07/2025] [Indexed: 02/20/2025]
Abstract
OBJECTIVES Inflammatory bowel disease (IBD) is an immune-mediated, chronic, remitting, and relapsing disease. Calprotectin, used in monitoring the disease activity, is expressed from neutrophilic granulocytes during inflammation. Neutrophil gelatinase-associated lipocalin (NGAL) is strongly expressed in both granulocytes and the intestinal epithelial cell layer. The aim of the study was to compare fecal NGAL (FNGAL) with fecal calprotectin (FCAL) in children with IBD. METHODS Forty-four children with IBD and 22 healthy children were included in the study. The patients were divided into two groups, patients with active disease and remission group. Clinical and demographic characteristics, disease activity scores, and serum and fecal markers of the patients were recorded. RESULTS The mean age of the patients was 13.2 ± 3.4 years (range 6-17 years) and male/female: 0.62. FNGAL levels of patients with active disease were higher than those in the remission group (p < 0.001). A statistically significant positive correlation was observed between Pediatric Ulcerative Colitis Activity Index scores and white blood cell count, platelets, neutrophil-to-albumin ratio (NAR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and FNGAL. There was a positive correlation between Pediatric Crohn's Disease Activity Index scores and platelets, NAR, ESR, CRP, and FNGAL, whereas there was a statistically significantly negative correlation with activity scores and albumin. While FNGAL had 95.5% sensitivity and 81.8% specificity, FCAL had 86.7% sensitivity and 85.7% specificity. CONCLUSIONS FNGAL levels were found to be high and sensitive in determining disease activity in our patients with IBD, suggesting that it may be a valuable biomarker.
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Affiliation(s)
- Aysenur Kardas Yildiz
- Department of Pediatrics, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Nafiye Urganci
- Department of Pediatric Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ayşe Merve Usta
- Department of Pediatric Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
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Sinclair J, McLaughlin G, Allan R, Brooks-Warburton J, Lawson C, Goh S, Desai T, Bottoms L. Health Benefits of Montmorency Tart Cherry Juice Supplementation in Adults with Mild to Moderate Ulcerative Colitis; A Placebo Randomized Controlled Trial. Life (Basel) 2025; 15:306. [PMID: 40003718 PMCID: PMC11857002 DOI: 10.3390/life15020306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
AIMS Ulcerative colitis (UC) significantly impacts individuals' self-perception, body image, and overall quality of life, while also imposing considerable economic costs. These challenges highlight the necessity for complementary therapeutic strategies with reduced adverse effects to support conventional pharmacological treatments. Among natural interventions, Montmorency tart cherries, noted for their high anthocyanin content have emerged as a natural anti-inflammatory agent for UC. The current trial aimed to investigate the effects of Montmorency tart cherries compared to placebo in patients with mild to moderate UC. MATERIALS AND METHODS Thirty-five patients with UC were randomly assigned to receive either placebo or Montmorency tart cherry juice, of which they drank 60 mL per day for 6 weeks. The primary outcomes and health-related quality of life, measured via the Inflammatory Bowel Disease Quality of Life Questionnaire (IBDQ), and the secondary measures, including other health-related questionnaires, blood biomarkers, and faecal samples, were measured before and after the intervention. Linear mixed-effects models were adopted to contrast the changes from baseline to 6 weeks between trial arms. Effect sizes were calculated using Cohen's d. RESULTS There were significantly greater improvements in the IBDQ (22.61 (95% CI = 5.24 to 39.99) d = 0.90) and simple clinical colitis activity index (-3.98 (95% CI = -6.69 to -1.28) d = -1.01) in the tart cherry trial arm compared to placebo. In addition, reductions in faecal calprotectin levels were significantly greater in the tart cherry trial arm compared to placebo (-136.17 µg/g (95% CI = -258.06 to -4.28) d = -1.14). Loss to follow-up (N = 1) and adverse events (N = 1) were low and compliance was very high in the tart cherry (95.8%) trial arm. CONCLUSIONS Given the profoundly negative effects of UC on health-related quality of life and its fiscal implications for global healthcare systems, this trial indicates that twice-daily tart cherry supplementation can improve IBD-related quality of life as well as the severity of symptoms and therefore may be important in the management of UC.
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Affiliation(s)
- Jonathan Sinclair
- Research Centre for Applied Sport, Physical Activity and Performance, School of Health Social Work & Sport, University of Central Lancashire, Preston PR1 2HE, UK
| | - Graham McLaughlin
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
| | - Robert Allan
- Research Centre for Applied Sport, Physical Activity and Performance, School of Health Social Work & Sport, University of Central Lancashire, Preston PR1 2HE, UK
| | - Johanne Brooks-Warburton
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
- Gastroenterology Department, Lister Hospital, Stevenage SG1 4AB, UK
| | - Charlotte Lawson
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
| | - Shan Goh
- Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
| | - Terun Desai
- Division of Surgery & Interventional Science, University College London, London WC1E 6BT, UK
| | - Lindsay Bottoms
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
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Tyrode G, Rivière P, Sebastian S, Poullenot F, Vuitton L, Laharie D. Systematic review: severe endoscopic lesions in inflammatory bowel disease. J Crohns Colitis 2025; 19:jjaf029. [PMID: 39968931 DOI: 10.1093/ecco-jcc/jjaf029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Indexed: 02/20/2025]
Abstract
BACKGROUND Endoscopy and biopsy are the standard tools for the diagnosis of inflammatory bowel disease (IBD) and the assessment of treatment response. Severe endoscopic lesions (SEL) are commonly observed in IBD, but have been poorly described in the literature. The aim of this review is to provide an overview of the current understanding and gaps in knowledge about these lesions. METHODS We performed a systematic review of studies of SEL in patients with IBD. A search was performed in MEDLINE, Embase, and Cochrane CENTRAL databases in July 2024. Studies were eligible if they investigated SEL, its involvement in the disease, its evolution with treatment, and its prognostic implications. RESULTS We found 1172 articles in the Pubmed database and 46 were included. Of the various definitions of SEL used in the literature, most of them are based on the most severe endoscopic items from existing endoscopic scores, but none have been validated. Despite the paucity of literature, the prevalence of SEL is estimated to be 33%-75% in acute severe ulcerative colitis (ASUC) and 22.5%-87% in Crohn's disease (CD). In terms of prognosis, SEL are associated with steroid refractoriness in ASUC and do not affect response to infliximab or ciclosporin. In CD, the response to biologics, especially anti-TNF, is not affected by the presence of SEL. CONCLUSIONS There is currently no validated definition of SEL in IBD. When present, they are associated with steroid failure in the setting of ASUC, but do not affect response to anti-TNF in either CD or ASUC.
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Affiliation(s)
- Gaëlle Tyrode
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie et oncologie digestive, Université de Bordeaux, F-33000 Bordeaux, France
| | - Pauline Rivière
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie et oncologie digestive, Université de Bordeaux, F-33000 Bordeaux, France
| | - Shaji Sebastian
- IBD Unit, Hull University Teaching Hospitals NHS Trust, Hull, HU3 2JZ, United Kingdom
| | - Florian Poullenot
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie et oncologie digestive, Université de Bordeaux, F-33000 Bordeaux, France
| | - Lucine Vuitton
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France
| | - David Laharie
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie et oncologie digestive, Université de Bordeaux, F-33000 Bordeaux, France
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Harindranath S, Desai D. Wearable technology in inflammatory bowel disease: current state and future direction. Expert Rev Med Devices 2025; 22:121-126. [PMID: 39798078 DOI: 10.1080/17434440.2025.2453561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 12/30/2024] [Accepted: 01/10/2025] [Indexed: 01/13/2025]
Abstract
INTRODUCTION Wearables are electronic devices worn on the body to collect health data. These devices, like smartwatches and patches, use sensors to gather information on various health parameters. This review highlights the current use and the potential benefit of wearable technology in patients with inflammatory bowel disease (IBD). AREAS COVERED In this review, we explore the current use of wearable technology in healthcare and the studies applying this technology in patients with IBD. We also discuss the limitations of using digital health data in general and wearable technology in particular in the current clinical paradigm and predict a path forward in how to rationally and effectively apply this technology to improve the care of patients with IBD. A comprehensive search of all suitable studies was conducted using the databases of PubMed, MEDLINE, Embase, and Scopus from inception to August 2024. EXPERT OPINION Currently, wearable technology is applied to the monitoring of IBD and prediction of flares using devices and sensors. Future applications include early disease detection using biosensors, advanced data collection through ingestible devices, gut microbiome monitoring, and integration with machine learning. These advancements promise to revolutionize disease management, including IBD, by enabling early diagnosis, personalized treatment, and improved patient outcomes.
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Affiliation(s)
- Sidharth Harindranath
- Department of Gastroenterology, Seth GS medical college and KEM hospital, Mumbai, India
- Division of Gastroenterology, P.D Hinduja Hospital, Mumbai, India
| | - Devendra Desai
- Division of Gastroenterology, P.D Hinduja Hospital, Mumbai, India
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Karashima R, Sagami S, Yamana Y, Maeda M, Hojo A, Miyatani Y, Nakano M, Matsuda T, Hibi T, Kobayashi T. Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis. Intest Res 2024; 22:473-483. [PMID: 38835140 PMCID: PMC11534452 DOI: 10.5217/ir.2023.00135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 03/31/2024] [Accepted: 04/09/2024] [Indexed: 06/06/2024] Open
Abstract
BACKGROUND/AIMS Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated. METHODS Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed. RESULTS A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8. CONCLUSIONS LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.
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Affiliation(s)
- Ryo Karashima
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan
| | - Shintaro Sagami
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Yoko Yamana
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Masa Maeda
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Aya Hojo
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Yusuke Miyatani
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Masaru Nakano
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Takahisa Matsuda
- Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
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Gibble TH, Shan M, Zhou X, Naegeli AN, Dubey S, Lewis JD. Association of fatigue with disease activity and clinical manifestations in patients with Crohn's disease and ulcerative colitis: an observational cross-sectional study in the United States. Curr Med Res Opin 2024; 40:1537-1544. [PMID: 39037798 DOI: 10.1080/03007995.2024.2380733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 05/28/2024] [Accepted: 07/12/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND Fatigue imposes a socioeconomic burden on patients with Crohn's disease (CD) and ulcerative colitis (UC). We assessed the prevalence of fatigue among patients with CD or UC and identified disease activity measures associated with fatigue. METHODS Data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed separately for CD and UC. Fatigue was defined based on a subjective and dichotomic questionnaire. Patients indicated if they experienced fatigue within the last week. The overall prevalence of fatigue was analyzed using descriptive and contingency tables. Demographics, clinical characteristics, disease activity (measures include Physician's Global Assessment for both CD and UC, short CD Activity Index for CD, and Ulcerative Colitis Disease Activity Index for UC), symptoms, and patient-reported outcomes were compared between patients with and without fatigue. Multivariable logistic regression models were constructed to identify symptoms and disease activity measures associated with fatigue. RESULTS The study included 903 patients with CD and 443 patients with UC. Fatigue was reported in 47.7% of patients with CD and 40.9% of patients with UC. In patients with CD, abdominal pain, bowel incontinence, depressive symptoms, reduced general well-being, and night-time bowel movements were associated with fatigue. In patients with UC, depressive symptoms, reduced general well-being, moderate or severe disease activity by the physician's global assessment, and night-time bowel movements were significantly associated with fatigue. CONCLUSIONS Fatigue is a common symptom among patients with CD or UC and is associated with higher levels of disease activity and reduced general well-being.
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Affiliation(s)
| | | | | | | | | | - James D Lewis
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Xu C, Song Z, Hu LT, Tong YH, Hu JY, Shen H. Abnormal platelet parameters in inflammatory bowel disease: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:214. [PMID: 38961334 PMCID: PMC11221001 DOI: 10.1186/s12876-024-03305-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Platelet dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Despite clinical observations indicating abnormalities in platelet parameters among IBD patients, inconsistencies persist, and these parameters lack standardization for diagnosis or clinical assessment. METHODS A comprehensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases for relevant articles published up to December 16th, 2023. A random-effects model was employed to pool the weighted mean difference (WMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) between IBD patients and healthy controls, and subgroup analyses were performed. RESULTS The meta-analysis included 79 articles with 8,350 IBD patients and 13,181 healthy individuals. The results revealed significantly increased PLT and PCT levels (WMD: 69.910, 95% CI: 62.177, 77.643 109/L; WMD: 0.046%, 95% CI: 0.031%, 0.061%), and decreased MPV levels (WMD: -0.912, 95% CI: -1.086, -0.739 fL) in IBD patients compared to healthy individuals. No significant difference was found in PDW between the IBD and control groups (WMD: -0.207%, 95% CI: -0.655%, 0.241%). Subgroup analysis by disease type and disease activity showed no change in the differences for PLT, PCT, and MPV in the ulcerative colitis and Crohn's disease groups, as well as the active and inactive groups. Notably, the active group exhibited significantly lower PDW levels than the control group (WMD: -1.138%, 95% CI: -1.535%, -0.741%). CONCLUSIONS Compared with healthy individuals, IBD patients display significantly higher PLT and PCT and significantly lower MPV. Monitoring the clinical manifestations of platelet abnormalities serves as a valuable means to obtain diagnostic and prognostic information. Conversely, proactive measures should be taken to prevent the consequences of platelet abnormalities in individuals with IBD. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42023493848.
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Affiliation(s)
- Cheng Xu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhen Song
- Nanjing University of Chinese Medicine, Nanjing, China
- Yancheng Binhai Hospital of Traditional Chinese Medicine, Yancheng, China
| | - Li-Ting Hu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi-Heng Tong
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Jing-Yi Hu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
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Costa MHDM, Sassaki LY, Chebli JMF. Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease. World J Gastroenterol 2024; 30:3022-3035. [PMID: 38983953 PMCID: PMC11230062 DOI: 10.3748/wjg.v30.i24.3022] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 05/01/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.
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Affiliation(s)
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University (Unesp), Botucatu 18618-686, São Paulo, Brazil
| | - Júlio Maria Fonseca Chebli
- Division of Gastroenterology, Department of Medicine, University Hospital of The Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Juiz de Fora 36036-247, Minas Gerais, Brazil
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Oka A, Kawashima K, Kishimoto K, Kotani S, Fukunaga M, Fukuba N, Mishima Y, Oshima N, Ishimura N, Awoniyi M, Ishihara S. Validation of rapid fecal calprotectin assay using particle enhanced turbidimetric immunoassay for inflammatory bowel disease. Sci Rep 2024; 14:1653. [PMID: 38238442 PMCID: PMC10796650 DOI: 10.1038/s41598-024-51580-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 01/07/2024] [Indexed: 01/22/2024] Open
Abstract
Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.
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Affiliation(s)
- Akihiko Oka
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Kousaku Kawashima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan.
- Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan.
- Department of Internal Medicine, Matsue Seikyo General Hospital, Matsue, Shimane, Japan.
| | - Kenichi Kishimoto
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Satoshi Kotani
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Mai Fukunaga
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Nobuhiko Fukuba
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Yoshiyuki Mishima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Naoki Oshima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Norihisa Ishimura
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Muyiwa Awoniyi
- Department of Inflammation and Immunity, Digestive Disease and Surgery Institute, Division of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA
| | - Shunji Ishihara
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
- Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan
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11
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Saibeni S, Bezzio C, Bossa F, Privitera AC, Marchi S, Roselli J, Mazzuoli S, Geccherle A, Soriano A, Principi MB, Viola A, Sarpi L, Cappello M, D'Incà R, Mastronardi M, Bodini G, Guerra M, Benedetti A, Romano M, Cicala M, Di Sabatino A, Scaldaferri F, De Rosa T, Giardino AM, Germano V, Orlando A, Armuzzi A. Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study. Dig Liver Dis 2024; 56:83-91. [PMID: 37574431 DOI: 10.1016/j.dld.2023.07.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 07/25/2023] [Accepted: 07/28/2023] [Indexed: 08/15/2023]
Abstract
BACKGROUND In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.
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Affiliation(s)
- S Saibeni
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Milan, Italy
| | - C Bezzio
- IBD Unit, Gastroenterology IBD Unit, Rho Hospital, ASST Rhodense, Milan, Italy
| | - F Bossa
- Foudation Casa della Sofferenza, UOC Gastroenterology and Digestive Endoscopy, San Giovanni Rotondo, Foggia, Italy
| | | | - S Marchi
- Department of Translational Research, University of Pisa, Italy
| | - J Roselli
- Gastroenterology, Biomedical and Experimental and Clinical Sciences, "Mario Serio" University of Florence, Italy
| | - S Mazzuoli
- IBD Unit U.O.C. of Gastroenterology "Monsignor Raffaele Dimiccoli" Hospital, ASL Barletta, Italy
| | - A Geccherle
- IBD Unit IRCCS "Sacro Cuore-Don Calabria" Negrar di Valpolicella, Verona, Italy
| | - A Soriano
- Department of Internal Medicine, Gastroenterology Division and IBD Center, Azienda Unità Sanitaria Locale - IRCCS of Reggio Emilia Arcispedale S. Maria Nuova, 42121 Reggio Emilia, Italy
| | - M B Principi
- U.O.C. of Gastroenterology, "Azienda Policlinico- Universitaria", Bari, Italy
| | - A Viola
- Department of Clinical and Experimental Medicine, University of Messina, Italy
| | - L Sarpi
- Gastroenterology and Digestive Endoscpy, Hospital "Media Valle del Tevere" Pantalla -Todi, Perugia, Italy
| | - M Cappello
- Gastroenterology and Hepatology Section, Promise, University of Palermo, Italy
| | - R D'Incà
- U.O.C of Gastroenterology, "University Azienda", Padua, Italy
| | - M Mastronardi
- U.O.S IBD IRCCS "S. De Bellis" Castellana Grotte, Bari Italy
| | - G Bodini
- Policlinico San Martino, University of Genoa, Italy
| | - M Guerra
- Foudation Casa della Sofferenza, UOC Gastroenterology and Digestive Endoscopy, San Giovanni Rotondo, Foggia, Italy
| | - A Benedetti
- Clinic of Gastroenterology, Hepatology and Digestive Endoscopy, Università Politecnica delle Marche-Ospedali Riuniti, Ancona, Italy
| | - M Romano
- Precision Medicine Department, University "l. Vanvitelli" Naples, Italy
| | - M Cicala
- U.O.C. of Gastroenterology and Digestive Endoscopy, "Campus Bio Medico" University, Rome, Italy
| | - A Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - F Scaldaferri
- CEMAD (Digestive Disease Center) - UOS IBD UNIT, Fondazione Policlinico Universitario ‟A Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - T De Rosa
- Medical Affairs MSD Italy, Rome, Italy
| | | | - V Germano
- Medical Affairs MSD Italy, Rome, Italy
| | - A Orlando
- IBD Unit A.O. Ospedali Riuniti "Villa Sofia Cervello", Palermo, Italy
| | - A Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy.
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12
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Lee SB, Kim HK, Park SH, Lim JH, Park SH. Ischemia-modified albumin: a novel blood marker of endoscopic mucosal healing in inflammatory bowel disease. Intest Res 2024; 22:75-81. [PMID: 37904321 PMCID: PMC10850695 DOI: 10.5217/ir.2023.00065] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 08/11/2023] [Accepted: 08/29/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND/AIMS The achievement of endoscopic remission is an important therapeutic goal in the treatment of inflammatory bowel diseases (IBD). We aimed to evaluate the role of fecal calprotectin (FCP) and ischemia-modified albumin (IMA) as biomarkers for evaluating IBD disease activity. METHODS A total of 48 patients with IBD (20 with ulcerative colitis and 28 with Crohn's disease) were included in this study. FCP and serum C-reactive protein levels, erythrocyte sedimentation rate, and IMA were measured in patients with IBD and compared with endoscopic findings. RESULTS Elevated FCP and serum IMA levels were significantly associated with endoscopic non-mucosal healing. The correlation between FCP and IMA was not significant. Analysis of the receiver operating characteristic curve showed that both FCP and IMA had diagnostic value in predicting non-mucosal healing. When the Ln(FCP)+IMA/10 value was calculated using both factors, the predictive value for non-mucosal healing increased; however, no significant difference was observed. CONCLUSIONS IMA could be a candidate serum biomarker for predicting endoscopic mucosal healing in IBD.
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Affiliation(s)
- Seung Bum Lee
- Department of Gastroenterology Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Hyun-Ki Kim
- Department of Laboratory Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Sang Hyuk Park
- Department of Laboratory Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Ji-Hun Lim
- Department of Laboratory Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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13
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Newman KL, Higgins PDR. Fecal calprotectin level is nonlinearly associated with GI pathogen detection in patients with and without inflammatory bowel disease. J Clin Microbiol 2023; 61:e0094623. [PMID: 38038481 PMCID: PMC10729747 DOI: 10.1128/jcm.00946-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 10/12/2023] [Indexed: 12/02/2023] Open
Abstract
Fecal calprotectin (FCP) is used to monitor inflammatory bowel disease (IBD) activity and can also be elevated in gastrointestinal infections. Our study's objective was to quantify the relationship between FCP levels and lab-confirmed infections in people with and without IBD. We performed a cross-sectional study at a tertiary-care center of all encounters during which FCP and gastrointestinal pathogen polymerase-chain reaction (GI PCR) panel testings were conducted. Using non-parametric tests and quantile regression, we compared the FCP levels by IBD status and pathogen detection. There were 3,347 encounters with FCP and GI PCR testings from 2,780 unique individuals between 1 August 2016 and 17 February 2022. Overall, 54.4% had IBD (n = 1,819). Pathogens were detected in 744 encounters (22.2%), and the detection rate did not differ by IBD status. Median FCP without IBD was significantly elevated when a pathogen was detected (64 vs 41 mg/kg, P = 0.0003, normal ≤50.0 mg/kg), but FCP with IBD was not significantly elevated when a pathogen was detected (299 vs 255 mg/kg, P = 0.207). In quantile regression adjusted for age and IBD, pathogen detection was only significantly associated with higher FCP in the lower two quartiles, though IBD remained significantly associated with higher FCP at all levels (P > 0.001). Pathogen detection by GI PCR is associated with elevated FCP, though this relationship is nonlinear and varies by IBD status. Our findings indicate that FCP may be an adjunct to, but not a substitute for, stool pathogen testing.
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Affiliation(s)
- Kira L. Newman
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
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14
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Chen H, Lin X, Pan X, Xu H, Zhang X, Liang G, Qiu J, Zhang X, Gao Y, Tan X, Li N, Cai H, Cang X, Qi J, Li W, Li S, Zheng Y, Zhao L, Jin S. Development and validation of a blood routine-based extent and severity clinical decision support tool for ulcerative colitis. Sci Rep 2023; 13:21368. [PMID: 38049548 PMCID: PMC10696009 DOI: 10.1038/s41598-023-48569-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 11/28/2023] [Indexed: 12/06/2023] Open
Abstract
Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin's model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin's model was free with open access at http://jinmodel.com:3000/ . Jin's model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.
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Affiliation(s)
- Hongliang Chen
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Xindi Lin
- Department of Statistics, University of Wisconsin, Madison, WI, USA
| | - Xinyue Pan
- School of Economics and Finance, Xi'an Jiaotong University, Xi'an, China
| | - Hongyu Xu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xuemei Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China
| | - Guoying Liang
- Department of Liver, Spleen and Stomach Diseases, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jiawei Qiu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Xueyan Zhang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Yang Gao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Xin Tan
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ning Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Huimin Cai
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Xueyu Cang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Jihan Qi
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Wei Li
- Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China
| | - Shuang Li
- Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China
| | - Yutong Zheng
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Lei Zhao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China
| | - Shizhu Jin
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China.
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15
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Ogihara R, Kurumi H, Kanda T, Yashima K, Isomoto H, Yamaguchi N. Serum Activin A Is a Novel Biomarker of Endoscopic Activity in Ulcerative Colitis. Gastroenterology Res 2023; 16:334-341. [PMID: 38186584 PMCID: PMC10769608 DOI: 10.14740/gr1677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/16/2023] [Indexed: 01/09/2024] Open
Abstract
Background Endoscopic healing (EH) is the long-term therapeutic goal for ulcerative colitis (UC). Since repeated colonoscopies are inconvenient and invasive, a surrogate biomarker for endoscopic activity is needed. Activin A is one of the transforming growth factor-β superfamily of proteins and has been shown to be associated with intestinal inflammation. Methods This single-center observational study included 27 Japanese patients with UC in clinical remission who underwent colonoscopy and blood sampling. We investigated the correlations between laboratory parameters, including serum activin A levels, and endoscopic activity, classified by the Mayo endoscopic subscore (MES) in these patients. Results This study included 15 males and 12 females. The median age was 44.0 years. In terms of endoscopic activity, five patients were diagnosed with MES 0, 14 patients with MES 1, seven patients with MES 2, and one patient with MES 3. The median serum activin level was 134.8 pg/mL (interquartile range (IQR), 105.3 - 188.1). Serum activin A levels were significantly correlated with the MES (Spearman's rank correlation coefficient r = 0.591, P = 0.001), which was better than that of C-reactive protein (CRP) (r = 0.487, P = 0.010). In the comparison between the EH group (MES 0) and non-EH group (MES 1-3), patients without EH had significantly higher serum activin A levels (Mann-Whitney U test, P = 0.047). A cutoff value of 133.6 pg/mL indicated non-EH with a sensitivity and specificity of 0.682 and 1.000, respectively. The area under the curve (AUC) of serum activin A for detecting non-EH was 0.791 (95% confidence interval (CI), 0.618 - 0.964), while that of CRP was 0.723 (95% CI, 0.504 - 0.941). Conclusions The serum activin A level is a potential novel biomarker of endoscopic activity in UC.
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Affiliation(s)
- Ryohei Ogihara
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Hiroki Kurumi
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Tsutomu Kanda
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Kazuo Yashima
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Naoyuki Yamaguchi
- Department of Endoscopy, Nagasaki University Hospital, Nagasaki, Japan
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16
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Rimmer P, Iqbal T. Prognostic modelling in IBD. Best Pract Res Clin Gastroenterol 2023; 67:101877. [PMID: 38103929 DOI: 10.1016/j.bpg.2023.101877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 11/24/2023] [Indexed: 12/19/2023]
Abstract
In the ideal world prognostication or predicting disease course in any chronic condition would allow the clinician to anticipate disease behaviour, providing crucial information for the patient and data regarding best use of resources. Prognostication also allows an understanding of likely response to treatment and the risk of adverse effects of a treatment leading to withdrawal in any individual patient. Therefore, the ability to predict outcomes from the onset of disease is the key step to developing precision personalised medicine, which is the design of medical care to optimise efficiency or therapeutic benefit based on careful profiling of patients. An important corollary is to prevent unnecessary healthcare costs. This paper outlines currently available predictors of disease outcome in IBD and looks to the future which will involve the use of artificial intelligence to interrogate big data derived from various important 'omes' to tease out a more holistic approach to IBD.
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Affiliation(s)
- Peter Rimmer
- Queen Elizabeth Hospital Birmingham, B15 2TH, UK; University of Birmingham, College of Medical and Dental Science, UK.
| | - Tariq Iqbal
- Queen Elizabeth Hospital Birmingham, B15 2TH, UK; University of Birmingham, College of Medical and Dental Science, UK.
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17
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Neurath MF, Vieth M. Different levels of healing in inflammatory bowel diseases: mucosal, histological, transmural, barrier and complete healing. Gut 2023; 72:2164-2183. [PMID: 37640443 DOI: 10.1136/gutjnl-2023-329964] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 08/16/2023] [Indexed: 08/31/2023]
Abstract
Mucosal healing on endoscopy has emerged as a key prognostic parameter in the management of patients with IBD (Crohn's disease, ulcerative colitis/UC) and can predict sustained clinical remission and resection-free survival. The structural basis for this type of mucosal healing is a progressive resolution of intestinal inflammation with associated healing of ulcers and improved epithelial barrier function. However, in some cases with mucosal healing on endoscopy, evidence of histological activity in mucosal biopsies has been observed. Subsequently, in UC, a second, deeper type of mucosal healing, denoted histological healing, was defined which requires the absence of active inflammation in mucosal biopsies. Both levels of mucosal healing should be considered as initial events in the resolution of gut inflammation in IBD rather than as indicators of complete transmural healing. In this review, the effects of anti-inflammatory, biological or immunosuppressive agents as well as small molecules on mucosal healing in clinical studies are highlighted. In addition, we focus on the implications of mucosal healing for clinical management of patients with IBD. Moreover, emerging techniques for the analysis of mucosal healing as well as potentially deeper levels of mucosal healing such as transmural healing and functional barrier healing of the mucosa are discussed. Although none of these new levels of healing indicate a definitive cure of the diseases, they make an important contribution to the assessment of patients' prognosis. The ultimate level of healing in IBD would be a resolution of all aspects of intestinal and extraintestinal inflammation (complete healing).
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Affiliation(s)
- Markus F Neurath
- Medical Clinic 1 & Deutsches Zentrum Immuntherapie DZI, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Michael Vieth
- Pathology Clinic, Klinikum Bayreuth GmbH, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bayreuth, Germany
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18
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Asiri AS, Algarni SS, Althubaiti AQ, Alzubaidi MA, Alghamdi JA, Almalki GA. Fecal Calprotectin and Organic Gastrointestinal Disease: A Systematic Review. Cureus 2023; 15:e45019. [PMID: 37829963 PMCID: PMC10565882 DOI: 10.7759/cureus.45019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/11/2023] [Indexed: 10/14/2023] Open
Abstract
This review aimed to assess the diagnostic utility of fecal calprotectin (FCP) for identifying organic gastrointestinal disease (OGID) in patients undergoing colonoscopy for gastrointestinal discomfort or active progression of inflammatory bowel disease (IBD). Studies published between January 2013 and December 2022 evaluating the clinical efficacy of FCP for differentiating OGID against functional gastrointestinal disease (FGID) were identified using PubMed, Cochrane, and Scopus databases. Clinical diagnostic studies involving individuals with lower gastrointestinal symptoms; using FCP as a diagnostic biomarker either in primary, secondary, or tertiary healthcare centers conducted either prospectively or retrospectively using stool samples (index test), contrasting FCP with a reference test, such as colonoscopy, or endoscopy, and assessed using enzyme-linked immunosorbent assay were reviewed. The included studies were subjected to the revised Quality Assessment of Diagnostic Accuracy Studies for assessing the methodological quality by two independent authors. An initial literature search yielded 545 articles rendering 417 records after removing the duplicate records. After reading the abstracts and titles, 89 articles were eligible for full-text screening. The qualitative synthesis resulted in 20 articles. The efficient use of FCP for differentiating IBD from irritable bowel syndrome was investigated in 15 studies.Two of the included studies assessed the diagnostic ability of FCP to distinguish OGID from FGID, two studies utilized patients with ulcerative colitis, and one study involved patients with Crohn's disease. Overall study quality was high for 65% of studies,moderate for 25% of studies, and low for 10% of studies. The review outlined the diagnostic accuracy of non-invasive FCP assessment for OGID in various clinical scenarios and in individuals of various ages. FCP is used as a tool for screening and monitoring in clinical practice for determining the need of further comprehensive investigations, thereby reducing the redundant use of invasive techniques.
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Affiliation(s)
| | - Saad S Algarni
- Internal Medicine, Comprehensive Specialized Clinics for Security forces, Jeddah, SAU
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19
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Zahmatkesh A, Sohouli MH, Hosseini SME, Rohani P. The role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in the diagnosis and severity of inflammatory bowel disease in children. Eur J Pediatr 2023; 182:4263-4270. [PMID: 37458815 DOI: 10.1007/s00431-023-05110-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 07/05/2023] [Accepted: 07/08/2023] [Indexed: 10/14/2023]
Abstract
Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric inflammatory bowel disease (IBD). We analyzed 73 pediatric patients with IBD with a retrospective study design who underwent measurement of fecal calprotectin (FC) and endoscopy and 67 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. We also plotted the ROC diagrams separately for markers to obtain the optimal point and a suitable cutoff point. We enrolled 73 pediatric patients less than 18 years of age with IBD, 40 subjects with UC and 33 with CD and 67 healthy subjects as control group with median age of 9.00 ± 4.61 in all subjects. Furthermore, the mean score of PCDAI or PUCAI in the all subjects was 19.26 ± 16.31. In the ROC curve, the optimal cutoff value for NLR and PLR for detecting IBD was 2.04 (sensitivity 82.1%; specificity 82.9%) and 103 (sensitivity 67.9%; specificity 71.4%). Also, the optimal cutoff values for NLR and PLR for differentiating IBD severity (remission vs. active disease) were 2.94 (sensitivity 77.8%; specificity 50.0%) and 157 (sensitivity 88.9%; specificity 54.5%), respectively. CONCLUSION Our findings indicate the role of easy and non-invasive markers such as NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease. WHAT IS KNOWN • NLR and PLR are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. WHAT IS NEW • In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric IBD. • Our findings indicate the role of NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease.
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Affiliation(s)
- Arefeh Zahmatkesh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Sohouli
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Pediatrics Gastroenterology, Department of Pediatrics, School of Medicine Childrens Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
| | | | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Pediatrics Gastroenterology, Department of Pediatrics, School of Medicine Childrens Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
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20
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Kapel N, Ouni H, Benahmed NA, Barbot-Trystram L. Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseases. Clin Transl Gastroenterol 2023; 14:e00617. [PMID: 37440723 PMCID: PMC10522095 DOI: 10.14309/ctg.0000000000000617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 06/13/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Calprotectin is a heterodimeric calcium- and zinc-binding protein mainly derived from the cytoplasm of neutrophils that has direct antimicrobial functions and a role in the regulation of the innate immune response. It can be found in various biological compartments, in particular, the stool, with concentrations related to the level of mucosal inflammation. The measurement of fecal calprotectin has thus been recognized as a useful surrogate marker to distinguish patients with inflammatory bowel disease from those with irritable bowel syndrome. Moreover, it allows the monitoring of intestinal inflammation with a high negative predictive value, making it possible to exclude the diagnosis of inflammatory bowel disease for symptomatic patients. It also shows high sensitivity for the identification of patients requiring additional examinations for diagnosis, such as colonoscopy, and the evaluation of therapeutic responses, providing evidence of relapse or mucosal healing, which can lead to the intensification or reduction of treatment. As calprotectin levels are a measure of mucosal inflammation, high fecal concentrations are also found in other diseases with an inflammatory component, such as infectious enteritis or colorectal cancer. Interpretation of the concentration must therefore always take into account the clinical history and symptoms specific to each patient.
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Affiliation(s)
- Nathalie Kapel
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
- INSERM UMR-S1139, Faculté de Pharmacie, Université de Paris Cité, Paris, France
| | - Hamza Ouni
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Nacer Adam Benahmed
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Laurence Barbot-Trystram
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
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21
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Iordache MM, Belu AM, Vlad SE, Aivaz KA, Dumitru A, Tocia C, Dumitru E. Calprotectin, Biomarker of Depression in Patients with Inflammatory Bowel Disease? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1240. [PMID: 37512053 PMCID: PMC10383955 DOI: 10.3390/medicina59071240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/22/2023] [Accepted: 06/28/2023] [Indexed: 07/30/2023]
Abstract
Background and Objectives: Calprotectin is a marker for intestinal inflammation. Recent research suggests a link between inflammation and depression. This study assessed the association between the levels of calprotectin in patients from South-Eastern Europe and the severity of depression, anxiety, and quality of life. Materials and Methods: This cross-sectional study included 30 confirmed patients with Crohn's disease (CD) and ulcerative colitis (UC) who were assessed using clinical interviews for determining the severities of mental disorders (i.e., depression severity-PHQ-9, anxiety-GAD-7) and the quality of life (EQ-5D). Stool samples were collected from all participants for measuring their levels of calprotectin. Results: The level of calprotectin is correlated with PHQ-9 (ρ = 0.416, p = 0.022) and EQ-5D (ρ = -0.304, p = 0.033) but not with GAD 7 (ρ = 0.059, p = 0.379). Calprotectin levels in patients with mild, moderate, and moderately severe depression were significantly higher than in patients with minimal depression (198 µg/g vs. 66,9 µg/g, p = 0.04). Calprotectin level was corelated with the following depressive symptoms: autolytic ideation (ρ = 0.557, p = 0.001), fatigue (ρ = 0.514, p = 0.002), slow movement (ρ = 0.490, p = 0.003), and sleep disorders (ρ = 0.403, p = 0.014). Calprotectin was an independent predictor of depression with an odds ratio of 1.01 (95%: 1.002-1.03, p < 0.01). An ROC analysis showed that a level of calprotectin of 131 µg/g or higher has a sensitivity of 82%, a specificity of 61%, and an accuracy of 70% for predicting depression. In this study, no significant correlations were found between calprotectin level and anxiety. Conclusions: Calprotectin levels are associated with the severity of depression, and checking for a calprotectin level of 131 µg/g or higher may be a potential accessible screening test for depression in patients with inflammatory bowel disease.
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Affiliation(s)
- Miorita Melina Iordache
- Faculty of Medicine, Ovidius University of Constanta, 1 Universitatii Alley, 900470 Constanta, Romania
- Prof. Alexandru Obregia Psychiatry Hospital, 10 Berceni Str., 041914 Bucharest, Romania
| | - Anca Mihaela Belu
- Faculty of Medicine, Ovidius University of Constanta, 1 Universitatii Alley, 900470 Constanta, Romania
- "St. Apostol Andrew" Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania
| | - Sabina E Vlad
- Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology-CEDMOG, "Ovidius" University of Constanta, 900591 Constanta, Romania
| | - Kamer Ainur Aivaz
- Faculty of Economics, Ovidius University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania
| | - Andrei Dumitru
- Faculty of Medicine, Ovidius University of Constanta, 1 Universitatii Alley, 900470 Constanta, Romania
- "St. Apostol Andrew" Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania
| | - Cristina Tocia
- Faculty of Medicine, Ovidius University of Constanta, 1 Universitatii Alley, 900470 Constanta, Romania
- "St. Apostol Andrew" Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania
| | - Eugen Dumitru
- Faculty of Medicine, Ovidius University of Constanta, 1 Universitatii Alley, 900470 Constanta, Romania
- "St. Apostol Andrew" Emergency County Hospital, 145 Tomis Blvd., 900591 Constanta, Romania
- Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology-CEDMOG, "Ovidius" University of Constanta, 900591 Constanta, Romania
- Academy of Romanian Scientists, 3 Ilfov Street, 050045 Bucharest, Romania
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22
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Pauwels RWM, Ten Bokkel Huinink S, van der Woude CJ, Doukas M, Oudijk L, de Vries AC. Early fecal calprotectin levels at week 8 may guide therapeutic decisions on Ustekinumab therapy in patients with Crohn's disease. Scand J Gastroenterol 2023; 58:980-987. [PMID: 36970968 DOI: 10.1080/00365521.2023.2194009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/12/2023] [Accepted: 03/19/2023] [Indexed: 05/16/2023]
Abstract
BACKGROUND Response evaluation after induction therapy with ustekinumab (UST) in Crohn's disease (CD) is important for decisions on maintenance therapy. We aimed to assess the potential of fecal calprotectin (FC) levels to predict endoscopic response at week 16. METHODS CD patients with FC >100 µg/g and endoscopic active disease (SES-CD> 2, Rutgeerts' score ≥ i2) at initiation of UST therapy were enrolled. FC was determined at weeks 0, 2, 4, 8 and 16 and patients underwent a colonoscopy at week 16. The primary outcome was an endoscopic response at week 16 (SES-CD score ≥50% decrease or a decrease of ≥1 points in Rutgeerts' score). The optimal cut-off levels of FC and change in FC to predict endoscopic response were determined using ROC statistics. RESULTS 59 CD patients were included. Endoscopic response was observed in 21/59 (36%) patients. The diagnostic accuracy for FC levels at week 8 to predict endoscopic response at week 16 showed a predictive value of 0.71. A decrease in FC levels ≥500 µg/g between baseline at week 8 indicates endoscopic response (PPV = 89%), whereas absence of any decrease indicates endoscopic non-response after induction (NPV = 81%). CONCLUSIONS Continuation of UST therapy without endoscopic response evaluation may be considered in patients with a decrease in FC levels of ≥500 µg/g at week 8. The decision on continuation of UST therapy or therapy optimization needs reconsideration in patients without a decrease of FC level. In all other patients, endoscopic response evaluation of induction therapy remains essential for therapeutic decisions.
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Affiliation(s)
- Renske W M Pauwels
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | | | | | - M Doukas
- Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - L Oudijk
- Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
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23
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Nowak JK, Kalla R, Satsangi J. Current and emerging biomarkers for ulcerative colitis. Expert Rev Mol Diagn 2023; 23:1107-1119. [PMID: 37933807 DOI: 10.1080/14737159.2023.2279611] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 11/01/2023] [Indexed: 11/08/2023]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic illness requiring lifelong management that could be enhanced by personalizing care using biomarkers. AREAS COVERED The main biomarker discovery modalities are reviewed, highlighting recent results across the spectrum of applications, including diagnostics (serum anti-αvβ6 antibodies achieving an area under the curve [AUC] = 0.99; serum oncostatin M AUC = 0.94), disease activity assessment (fecal calprotectin and serum trefoil factor 3: AUC > 0.90), prognostication of the need for treatment escalation (whole blood transcriptomic panels and CLEC5A/CDH2 ratio: AUC > 0.90), prediction of treatment response, and early identification of patients with subclinical disease. The use of established biomarkers is discussed, along with new evidence regarding autoantibodies, proteins, proteomic panels, transcriptomic signatures, deoxyribonucleic acid methylation patterns, and UC-specific glycomic and metabolic disturbances. EXPERT OPINION Novel biomarkers will pave the way for optimized UC care. However, validation, simplification, and direct clinical translation of complex models may prove challenging. Currently, few candidates exist to assess key characteristics, such as UC susceptibility, histological disease activity, drug response, and long-term disease behavior. Further research will likely not only reveal new tools to tackle these issues but also contribute to understanding UC pathogenesis mechanisms.
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Affiliation(s)
- Jan K Nowak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Rahul Kalla
- Medical Research Council Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Jack Satsangi
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, Oxford, UK
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24
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Cheah E, Huang JG. Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies. World J Gastroenterol 2023; 29:1539-1550. [PMID: 36970587 PMCID: PMC10037250 DOI: 10.3748/wjg.v29.i10.1539] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/17/2023] [Accepted: 02/22/2023] [Indexed: 03/14/2023] Open
Abstract
The advent of biologics and small molecules in inflammatory bowel disease (IBD) has marked a significant turning point in the prognosis of IBD, decreasing the rates of corticosteroid dependence, hospitalizations and improving overall quality of life. The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies. Biologics do not yet represent a complete panacea: A subset of patients do not respond to first-line anti-tumor necrosis factor (TNF)-alpha agents or may subsequently demonstrate a secondary loss of response. Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics. It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents. The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease. This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
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Affiliation(s)
- Eric Cheah
- Department of Gastroenterology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Parkville, VIC 3052, Australia
| | - James Guoxian Huang
- Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore 119228, Singapore
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
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25
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Cheah E, Huang JG. Precision medicine in inflammatory bowel disease: Individualizing the use of biologics and small molecule therapies. World J Gastroenterol 2023; 29:1395-1406. [DOI: 10.3748/wjg.v29.i10.1395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/10/2023] Open
Abstract
The advent of biologics and small molecules in inflammatory bowel disease (IBD) has marked a significant turning point in the prognosis of IBD, decreasing the rates of corticosteroid dependence, hospitalizations and improving overall quality of life. The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies. Biologics do not yet represent a complete panacea: A subset of patients do not respond to first-line anti-tumor necrosis factor (TNF)-alpha agents or may subsequently demonstrate a secondary loss of response. Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics. It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents. The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease. This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
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Affiliation(s)
- Eric Cheah
- Department of Gastroenterology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Parkville, VIC 3052, Australia
| | - James Guoxian Huang
- Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore 119228, Singapore,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
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26
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Del Hoyo J, Millán M, Garrido-Marín A, Aguas M. Are we ready for telemonitoring inflammatory bowel disease? A review of advances, enablers, and barriers. World J Gastroenterol 2023; 29:1139-1156. [PMID: 36926667 PMCID: PMC10011957 DOI: 10.3748/wjg.v29.i7.1139] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/02/2022] [Accepted: 02/09/2023] [Indexed: 02/21/2023] Open
Abstract
This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease (IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in PubMed, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through mHealth applications. Web systems demonstrated patients’ acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients´ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users´ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.
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Affiliation(s)
- Javier Del Hoyo
- Department of Gastroenterology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| | - Mónica Millán
- Department of Surgery, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| | - Alejandro Garrido-Marín
- Department of Gastroenterology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| | - Mariam Aguas
- Department of Gastroenterology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
- Health Research Institute La Fe, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
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27
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Hiraga H, Chinda D, Hasui K, Murai Y, Maeda T, Higuchi N, Ogasawara K, Kudo S, Sawada Y, Tatsuta T, Kikuchi H, Ebina M, Hiraga N, Mikami T, Sakuraba H, Fukuda S. Evaluation of Crohn's Disease Small-Bowel Mucosal Healing Using Capsule Endoscopy and Usefulness of Leucine-Rich α2-Glycoprotein. Diagnostics (Basel) 2023; 13:diagnostics13040626. [PMID: 36832114 PMCID: PMC9955912 DOI: 10.3390/diagnostics13040626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/30/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Recently, the importance of achieving clinical and deep remissions with mucosal healing (MH) has been demonstrated as a therapeutic goal to avoid Crohn's disease (CD) surgical operations. Although ileocolonoscopy (CS) is considered the gold standard, there are increasing reports on the benefits of capsule endoscopy (CE) and serum leucine-rich α2-glycoprotein (LRG) for evaluating small-bowel lesions in CD. We evaluated the data of 20 patients with CD who underwent CE in our department between July 2020 and June 2021 and whose serum LRG level was measured within 2 months. Concerning the mean LRG value, there was no significant difference between the CS-MH and CS-non-MH groups. Conversely, the mean LRG level was 10.0 μg/mL in seven patients in the CE-MH group and 15.2 μg/mL in 11 patients in the CE-non-MH group with a significant difference between the two groups (p = 0.0025). This study's findings show that CE can sufficiently determine total MH in most cases, and LRG is useful for evaluating CD small-bowel MH because of its correlation with CE-MH. Furthermore, satisfying CS-MH criteria and a cut-off value of 13.4 μg/mL for LRG suggests its usefulness as a CD small-bowel MH marker, which could be incorporated into the treat-to-target strategy.
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Affiliation(s)
- Hiroto Hiraga
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Daisuke Chinda
- Division of Endoscopy, Hirosaki University Hospital, Hirosaki 036-8563, Japan
- Correspondence: ; Tel.: +81-172-33-5111
| | - Keisuke Hasui
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Yasuhisa Murai
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Takato Maeda
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Naoki Higuchi
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Kohei Ogasawara
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Sae Kudo
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Yohei Sawada
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Tetsuya Tatsuta
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Hidezumi Kikuchi
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Mami Ebina
- Division of Endoscopy, Hirosaki University Hospital, Hirosaki 036-8563, Japan
| | - Noriko Hiraga
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Tatsuya Mikami
- Center of Healthy Aging Innovation, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Hirotake Sakuraba
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Shinsaku Fukuda
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
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28
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iSTART-II: An Update on the i Support Therapy-Access to Rapid Treatment (iSTART) Approach for Patient-Centered Therapy in Mild-to-Moderate Ulcerative Colitis. J Clin Med 2023; 12:jcm12031142. [PMID: 36769791 PMCID: PMC9918267 DOI: 10.3390/jcm12031142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/02/2023] [Accepted: 01/29/2023] [Indexed: 02/04/2023] Open
Abstract
The i Support Therapy-Access to Rapid Treatment (iSTART) was an initiative to improve patient-centered management in mild-to-moderate ulcerative colitis (UC). Our aim was to update the iSTART recommendations in order to include fecal calprotectin (FC) in the monitoring of patients with UC and improve their management. Twelve physicians from nine countries worldwide attended a virtual international consensus meeting on 4 May 2022. Data from three systematic reviews were analyzed, and a new systematic review investigating all studies reporting measurement of FC at home was conducted. Based on literature evidence, statements were formulated, discussed, and approved by voting. Statements were considered approved if at least 75% of participants agreed with a proposed statement. Fourteen statements were approved. Based on this consensus, FC measurement should be routinely performed for monitoring patients with mild-to-moderate UC to identify disease relapses early and initiate an appropriate treatment. Further studies are needed to assess whether self-monitoring of FC is associated with better disease control and improved patients' quality of life.
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29
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Dulai PS, Feagan BG, Sands BE, Chen J, Lasch K, Lirio RA. Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis. Clin Gastroenterol Hepatol 2023; 21:456-466.e7. [PMID: 35934286 DOI: 10.1016/j.cgh.2022.07.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 06/30/2022] [Accepted: 07/18/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND & AIMS We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. METHODS This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. RESULTS The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%-79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78-5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83-6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77-8.14; Geboes grade: OR, 6.42; 95% CI, 4.02-10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130-0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389-0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. CONCLUSIONS Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
| | - Brian G Feagan
- Robarts Clinical Trials, Western University, London, Ontario, Canada
| | - Bruce E Sands
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jingjing Chen
- Statistics and Quantitative Sciences, Takeda Development Center Americas, Inc, Cambridge, Massachusetts
| | - Karen Lasch
- US Medical Office, Takeda Pharmaceuticals U.S.A Inc., Lexington, Massachusetts
| | - Richard A Lirio
- Clinical Science, Takeda Development Center Americas, Inc., Cambridge, Massachusetts
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30
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Kawamura T, Yamamura T, Nakamura M, Maeda K, Sawada T, Ishikawa E, Iida T, Mizutani Y, Ishikawa T, Kakushima N, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M. Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease. Inflamm Bowel Dis 2023; 29:245-253. [PMID: 35436345 DOI: 10.1093/ibd/izac076] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. METHODS Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. RESULTS Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. CONCLUSIONS Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.
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Affiliation(s)
- Tatsuya Kawamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Keiko Maeda
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Tsunaki Sawada
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Naomi Kakushima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
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Anindita B, Sugihartono T, Miftahussurur M, Maimunah U, Nusi IA, Setiawan PB, Purbayu H, Kholili U, Widodo B, Thamrin H, Vidyani A, Rezkitha YAA, Yamaoka Y. High levels of fecal calprotectin and C-reactive protein in patients with colitis. J Med Life 2023; 16:48-51. [PMID: 36873123 PMCID: PMC9979164 DOI: 10.25122/jml-2021-0311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 09/22/2022] [Indexed: 03/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) with a poor prognosis may be due to persistent colitis. According to the latest guidelines, monitoring has become a part of the treatment process for colitis. Adequate monitoring of the patient's condition is necessary to determine the course of the disease to prevent the worsening of the condition and suppress the subclinical inflammatory process. This analytical study with a cross-sectional design was conducted to evaluate the activity of colitis using the results of C-reactive protein (CRP) and fecal calprotectin (FC) assays. FC levels were analyzed by ELISA, while CRP levels were analyzed using Siemens Flex particle-enhanced turbidimetric immunoassay. In 30 subjects with endoscopy and biopsy of colitis, 16 men and 14 women had a median age of 52.5 (18-70) years. The median FC value increased by 67 (7.3-722 g/g) and was positive (≥50 g/g) in 20 subjects (66.7%), and the mean CRP value was 13.64 mg/L, positive (10-15 mg/L) in 13 subjects (43.33%), and negative (<10 mg/L) in 17 subjects (56.67%). This study demonstrated that FC had a significant relationship with CRP (r=0.57; p<0.001) in patients with colitis. Assessing the levels of FC and CRP among patients with colitis can be useful to assess the worsening of symptoms early and reduce mortality and morbidity.
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Affiliation(s)
- Brinna Anindita
- Department of Internal Medicine, Dr. Soetomo Teaching Hospital, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia
| | - Titong Sugihartono
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.,Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Ummi Maimunah
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Iswan Abbas Nusi
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Poernomo Boedi Setiawan
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Herry Purbayu
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Ulfa Kholili
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Budi Widodo
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Husin Thamrin
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Amie Vidyani
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Yudith Annisa Ayu Rezkitha
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Internal Medicine, Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Yoshio Yamaoka
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
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Pediatric inflammatory bowel disease: Fecal calprotectin response to Anti-tumor necrosis factor alpha. Pediatr Res 2023; 93:131-136. [PMID: 35379929 DOI: 10.1038/s41390-022-02045-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/19/2021] [Accepted: 03/06/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Fecal calprotectin (FC) is a marker of mucosal inflammation in inflammatory bowel disease (IBD). We aimed to assess the effect of anti-tumor necrosis factor alpha (TNFα) therapy on FC levels in children with IBD. METHODS The medical records of pediatric patients treated with anti-TNFα agents (2015-2020) were reviewed retrospectively. 63 patients had FC levels measured prior to anti TNFα induction with sequential measurements during follow-up. The main outcome measures were time to FC response according to cutoffs of 250, 150, 100 and 50 µgr/gr. RESULTS Mean age was 13.6 ± 3 years [females 28 (44.4%), Crohn's 55 (87%)]. Outcomes of < 250, < 150, < 100 and < 50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%), respectively. The median time for achieving these cutoffs was 4.8 (1.8-15.6), 7.9 (2.6-16.4), 10.0 (3.5-20.5) and 18.5 (7.0-64.7) months, respectively. Shorter time from diagnosis to treatment was associated with achievement of FC < 50 µgr/gr (p = 0.03). There was no association between age, disease type, anti-TNFα type, inflammatory markers, disease activity indices at baseline and induction anti-TNFα trough concentration and FC response. CONCLUSIONS FC response was achieved by the majority of patients treated with anti-TNFα within a short period of time. FC normalization in responders required almost one year. IMPACT Fecal calprotectin response was achieved by the majority of pediatric patients within a relatively short period of time after anti-TNFα induction and maintenance therapy. Fecal calprotectin normalization required an average period of approximately one year in responders. The faster response of fecal calprotectin is associated with shorter time from diagnosis to anti-TNFα treatment. Inflammatory bowel disease treating physicians should be aware of the relatively prolonged time to fecal calprotectin normalization and to allow enough time for anti-TNFα therapy to express its full potential prior to significant interventions.
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Leung T, Long M, Horst S, Afzali A, Sapir T, Fajardo K, De Felice K, Sandler R, Cross R. A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and Persistence With Inflammatory Bowel Disease Therapy (ASSIST Study): Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2022; 11:e40382. [PMID: 36520519 PMCID: PMC9801266 DOI: 10.2196/40382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract. Although adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor. Consequently, there is a critical need to develop interventions that monitor adherence in real time and identify reasons for nonadherence to support clinical teams in initiating effective interventions. Recently, electronic- and web-based platforms have been developed to monitor adherence and guide interventions. A novel remote therapy monitoring (RTM) technology, the Tappt digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient-reported outcomes and barriers to care, and process patient data through algorithms that trigger personalized digital and human touch points between clinical visits. Such a digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. OBJECTIVE We propose a 12-month multicenter randomized controlled trial to assess the effectiveness of the Tappt digital health system on adherence, clinical outcomes, and health care use among patients diagnosed with IBD starting a new oral or subcutaneous therapy. METHODS The digital health system intervention will provide automatic measurement of medication adherence via smart labels for pill bottles or injectors as well as a monitoring platform for providers. The system will prompt patients to complete a two-item assessment of symptoms monthly using the PRO-2 scales for UC and Crohn disease, from which increased symptoms will be alerted to providers. Participants will be randomized 2:1 to the intervention group or the control group, which will receive standard of care. All participants are required to complete questionnaires at baseline as well as at 12, 26, and 52 weeks. Assuming an adherence rate of 0.65 and 0.9 among control and intervention participants, respectively, we will need to enroll 123 participants: 82 (66.7%) in the intervention group and 41 (33.3%) controls. We will compare adherence as measured by the medication possession ratio, defined as the number of days of supply of medication obtained during the observation period out of the total number of days in the observation period, in participants using the RTM versus those receiving standard of care. We will also compare clinical outcomes and health care use in participants using the RTM versus those receiving standard of care. RESULTS We anticipate starting recruitment in December 2022. CONCLUSIONS Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little or no burden to the patient, record reliable data in real time, and provide actionable insights to the health care team. We anticipate the Tappt digital health system to improve the medication possession ratio, clinical outcomes, and health care use compared with standard of care. TRIAL REGISTRATION ClinicalTrials.gov NCT05316584; https://clinicaltrials.gov/ct2/show/NCT05316584. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/40382.
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Affiliation(s)
| | - Millie Long
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Sara Horst
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Anita Afzali
- Division of Gastroenterology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | | | | | - Kara De Felice
- Division of Gastroenterology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Robert Sandler
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Raymond Cross
- Division of Gastroenterology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
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Vaghari-Tabari M, Alemi F, Zokaei M, Moein S, Qujeq D, Yousefi B, Farzami P, Hosseininasab SS. Polyphenols and inflammatory bowel disease: Natural products with therapeutic effects? Crit Rev Food Sci Nutr 2022; 64:4155-4178. [PMID: 36345891 DOI: 10.1080/10408398.2022.2139222] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Inflammatory bowel disease (IBD) is a long-life disease with periods of recurrence and relief. Oxidative stress plays an important role in the pathogenesis of this disease. Recent years' studies in the field of IBD treatment mostly have focused on targeting cytokines and immune cell trafficking using antibodies and inhibitors, altering the composition of intestinal bacteria in the line of attenuation of inflammation using probiotics and prebiotics, and attenuating oxidative stress through antioxidant supplementation. Studies in animal models of IBD have shown that some polyphenolic compounds including curcumin, quercetin, resveratrol, naringenin, and epigallocatechin-3-gallate can affect almost all of the above aspects and are useful compounds in the treatment of IBD. Clinical studies performed on IBD patients have also confirmed the findings of animal model studies and have shown that supplementation with some of the above-mentioned polyphenolic compounds has positive effects in reducing disease clinical and endoscopic activity, inducing and maintaining remission, and improving quality of life. In this review article, in addition to a detailed reviewing the effects of the above-mentioned polyphenolic compounds on the events involved in the pathogenesis of IBD, the results of these clinical studies will also be reviewed.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Forough Alemi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Zokaei
- Department of Food Science and Technology, Faculty of Nutrition Science, Food Science and Technology/National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Soheila Moein
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Bahman Yousefi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Payam Farzami
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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Matsumoto S, Mashima H. Usefulness of the Optimal Cutoff Value and Delta Value of Leucine-Rich Alpha 2 Glycoprotein in Ulcerative Colitis. CROHN'S & COLITIS 360 2022; 4:otac039. [PMID: 36778513 PMCID: PMC9681229 DOI: 10.1093/crocol/otac039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Indexed: 11/06/2022] Open
Abstract
Background Leucine-rich alpha 2 glycoprotein (LRG) is a novel serum biomarker used to determine disease activity in inflammatory bowel disease. We investigated the association between endoscopic scores based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and LRG in ulcerative colitis (UC). Methods A total of 1019 LRG measurements were obtained from 358 patients with UC. This study included 190 patients (199 measurements) who underwent colonoscopy within 3 months before and after LRG measurement with unchanged disease status or treatment during the same period. The patients were divided into those with and without UC relapse. We evaluated the correlation between LRG levels and UCEIS scores and performed a receiver operating characteristic curve analysis to determine the optimal LRG cutoff value. Delta values of LRG were then analyzed. Results LRG levels were positively correlated with UCEIS scores (correlation coefficient: 0.638; 95% CI: 0.548-0.714; P < .0001) in all disease types. The LRG cutoff value for mucosal healing was 12.6 µg mL-1 (area under the curve: 0.736; 95% CI: 0.651-0.821); this value had a sensitivity of 0.72 and a specificity of 0.66. In patients with UC relapse, the median delta value of LRG before and after relapse was 5 µg mL-1. Conclusions LRG levels were positively correlated with the UCEIS scores. The optimal LRG cutoff value for determining mucosal healing was 12.6 µg mL-1. The median delta value of LRG before and after relapse was 5 µg mL-1.
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Affiliation(s)
- Satohiro Matsumoto
- Address correspondence to: Satohiro Matsumoto, MD, PhD, Department of Gastroenterology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Omiya, Saitama, Saitama 330-8503, Japan ()
| | - Hirosato Mashima
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Saitama, Japan
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36
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Facciorusso A, Ramai D, Ricciardelli C, Paolillo R, Maida M, Chandan S, Mohan BP, Domislovic V, Sacco R. Prognostic Role of Post-Induction Fecal Calprotectin Levels in Patients with Inflammatory Bowel Disease Treated with Biological Therapies. Biomedicines 2022; 10:2305. [PMID: 36140408 PMCID: PMC9496232 DOI: 10.3390/biomedicines10092305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/09/2022] [Accepted: 09/14/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND There is currently scarce knowledge about markers of early therapeutic response in patients with inflammatory bowel disease (IBD) treated with biologics. The aim of this study was to evaluate the role of fecal calprotectin (FC) as an early predictor of mucosal healing and clinical remission. METHODS Data from a multicenter series of 172 IBD patients treated with biologics between 2017 and 2020 were analyzed. Treatment outcomes were mucosal healing and clinical remission assessed at 2 years. FC levels were assessed at 14 weeks (post-induction), at 6 months, and yearly. The receiver operating characteristic (ROC) curve analysis was performed to calculate the best cut-off in % change of FC levels between post-induction and baseline predicting treatment outcomes. Sensitivity, specificity, and accuracy for several post-induction FC cut-off points were also calculated. RESULTS At 2 years, mucosal healing was noted in 77 patients (44.7%), of whom were 41 Crohn's disease (CD) and 36 ulcerative colitis (UC) patients, whereas 106 patients experienced clinical remission (61.6%), of whom were 59 CD and 47 UC patients. Both baseline and post-induction FC levels were significantly higher in non-responders as compared to responders. On the other hand, FC decrease was less pronounced in non-responders. Similar results were observed in all subgroups, namely according to disease (CD vs. UC), or treatment used (TNF-inhibitors vs. vedolizumab). The best cut-off points were -86% in % change in FC levels to predict mucosal healing and -83% for clinical remission. CONCLUSIONS The current study suggests a predictive role of post-induction FC assessment to predict treatment response in IBD patients treated with biologics.
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Affiliation(s)
- Antonio Facciorusso
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Daryl Ramai
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA
| | - Cristina Ricciardelli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Rosa Paolillo
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, 93100 Caltanissetta, Italy
| | - Saurabh Chandan
- Gastroenterology Unit, CHI Health Creighton University Medical Center, Omaha, NE 68131, USA
| | - Babu P. Mohan
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA
| | - Viktor Domislovic
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
| | - Rodolfo Sacco
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, 71122 Foggia, Italy
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Ishida N, Kaneko M, Asai Y, Miyazu T, Tamura S, Tani S, Yamade M, Iwaizumi M, Hamaya Y, Osawa S, Furuta T, Sugimoto K. Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study. BMC Gastroenterol 2022; 22:420. [PMID: 36109718 PMCID: PMC9476332 DOI: 10.1186/s12876-022-02502-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/13/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.
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Affiliation(s)
- Natsuki Ishida
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Masanao Kaneko
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Yusuke Asai
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Takahiro Miyazu
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Satoshi Tamura
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
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Mc Gettigan N, Hanley M, Skelly F, Dowling J, Dunne R, Morrin MM, McCaffrey N, O'Toole A, Boland K. Impact of a physician-led exercise programme on quality of life, muscle mass and clinical response in inflammatory bowel disease patients during induction with disease-modifying therapy: a study protocol. BMJ Open Gastroenterol 2022. [DOI: 10.1136/bmjgast-2022-000959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
IntroductionBiologic and small-molecule therapies have revolutionised the treatment of moderate-to-severe inflammatory bowel disease (IBD). A significant proportion of patients experience early or delayed treatment failure. Patients with IBD with greater visceral obesity are less likely to respond to biologics. Sarcopenia has been identified as a predictor of disease severity and need for rescue therapy in acute severe ulcerative colitis. The aim of this study is to assess the feasibility of a physician-derived exercise programme in patients with IBD commencing biologic or small-molecule therapy in addition to the effect on physical fitness, body composition and objective measures of quality of life, fatigue scores and disease activity.Methods and analysisThis is a randomised controlled feasibility study comparing the effects of a physician-derived exercise programme and standard medical care (biologic/small-molecule therapy) with standard care alone in patients with moderate to severe IBD. Patients with IBD in the intervention group will undergo a structured exercise programme for 20 weeks. Both IBD groups will carry out body composition, disease activity and quality-of-life assessments at baseline, week 12 and week 26. The primary objective is to assess the feasibility of the physician-derived exercise programme in patients with IBD commencing disease-modifying therapies. Secondary endpoints include a change in cardiorespiratory fitness, disease activity/inflammation, fatigue, health-related quality of life outcomes and body composition between the two IBD groups. Exploratory endpoints include validation of anterior thigh ultrasound for sarcopenia screening, assessment of proinflammatory cytokines and markers of immunometabolism.Ethics and disseminationThis study has received ethical approval from the Beaumont Hospital Ethics committee on 22 October 2021 (reference number 21/21). Data generated or analysed during this study will be published as an article and supplementary appendix in relevant medical journals. The data will also be presented at national and international conferences.Trial registration numberNCT05174754.
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Wasserbauer M, Hlava S, Drabek J, Stovicek J, Minarikova P, Nedbalova L, Drasar T, Zadorova Z, Dolina J, Konecny S, Kojecky V, Kozeluhova J, Cernikova P, Pichlerova D, Kucerova B, Coufal S, Keil R. Adalimumab biosimilars in the therapy of Crohn´s disease and ulcerative colitis: Prospective multicentric clinical monitoring. PLoS One 2022; 17:e0271299. [PMID: 35939424 PMCID: PMC9359532 DOI: 10.1371/journal.pone.0271299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 06/27/2022] [Indexed: 12/22/2022] Open
Abstract
Objective The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab. Material and methods Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn’s disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn’s Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy. Results In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued. Conclusions This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.
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Affiliation(s)
- Martin Wasserbauer
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
| | - Stepan Hlava
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
- * E-mail:
| | - Jiri Drabek
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
| | - Jan Stovicek
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
| | - Petra Minarikova
- Department of Internal Medicine, 1st Faculty of Medicine, Military University Hospital, Charles University in Prague, Prague, Czech Republic
| | - Lenka Nedbalova
- Department for the Treatment of Non-specific Intestinal Inflammations - IBD Center Turnov, Hospital Turnov, Turnov, Czech Republic
| | - Tomas Drasar
- Department for the Treatment of Non-specific Intestinal Inflammations - IBD Center Turnov, Hospital Turnov, Turnov, Czech Republic
| | - Zdena Zadorova
- 2nd Department of Internal Medicine, 3rd Faculty of Medicine, FNKV, Charles University in Prague, Prague, Czech Republic
| | - Jiri Dolina
- Department of Internal Medicine and Gastroenterology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
| | - Stefan Konecny
- Department of Internal Medicine and Gastroenterology, Faculty of Medicine, University Hospital Brno, Masaryk University, Brno, Czech Republic
| | - Vladimír Kojecky
- Department of Internal Medicine, Regional Hospital of T. Baťa, Zlín, Czech Republic
| | - Jana Kozeluhova
- 2nd Department of Internal Medicine, University Hospital Plzeň - Bory, Plzeň, Czech Republic
| | - Pavlina Cernikova
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
| | - Dita Pichlerova
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
| | - Barbora Kucerova
- Department of Pediatric Surgery, 2nd Faculty of Medicine, University Hospital Motol, Charles University in Prague, Prague, Czech Republic
| | - Stepan Coufal
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
| | - Radan Keil
- Department of Internal Medicine, 2nd Faculty of Medicine, Motol University Hospital, Charles University in Prague, Prague, Czech Republic
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Ollech JE, Bannon L, Maharshak N, Bar N, Goren I, Tulchinsky H, Yanai H, Dotan I. Fecal Calprotectin Is Increased in Pouchitis and Progressively Increases With More Severe Endoscopic and Histologic Disease. Clin Gastroenterol Hepatol 2022; 20:1839-1846.e2. [PMID: 34798336 DOI: 10.1016/j.cgh.2021.11.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/22/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA. METHODS A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18). RESULTS Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] μg/g vs 550 [IQR, 250-1051] μg/g; P < .0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of >460 μg/g had >80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of <125 μg/g had over 80% specificity in predicting endoscopic remission. CONCLUSIONS FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA.
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Affiliation(s)
- Jacob E Ollech
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Lian Bannon
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Internal Medicine Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Nitsan Maharshak
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Unit, Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Nir Bar
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Unit, Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Idan Goren
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hagit Tulchinsky
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Colorectal Unit, Division of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Iris Dotan
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
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Sahu P, Jain S, Kedia S, Vuyyuru SK, Sahni P, Sharma R, Panwar R, Das P, Gupta V, Makharia G, Travis S, Ahuja V. Prospective validation of AIIMS index as a predictor of steroid failure in patients with acute severe ulcerative colitis. Indian J Gastroenterol 2022; 41:273-283. [PMID: 35474175 DOI: 10.1007/s12664-021-01217-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 07/19/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 μg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. METHODS IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. RESULTS Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 μg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 μg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. CONCLUSION AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%).
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Affiliation(s)
- Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Peush Sahni
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Rajesh Panwar
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Vipin Gupta
- Translational, Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, USA
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Simon Travis
- Translational, Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, USA
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India.
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Ge C, Lu Y, Shen H, Zhu L. Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis. Scand J Gastroenterol 2022; 57:513-524. [PMID: 34994661 DOI: 10.1080/00365521.2021.2022193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Ulcerative colitis is a chronic recurrent intestinal inflammatory disease, and its recurrence is difficult to predict. In this review, we summarized the objective indicators that can be used to evaluate intestinal inflammation, the purpose is to better predict the clinical recurrence of UC, formulate individualized treatment plan during remission of UC, and improve the level of diagnosis and treatment of UC.Methods: Based on the search results in the PUBMED database, we explored the accuracy and value of these methods in predicting the clinical recurrence of UC from the following three aspects: endoscopic and histological scores, serum biomarkers and fecal biomarkers.Results: Colonoscopy with biopsy is the gold standard for assessing intestinal inflammation, but it is invasive, inconvenient and expensive. At present, there is no highly sensitive and specific endoscopic or histological score to predict the clinical recurrence of UC. Compared with serum biomarkers, fecal biomarkers have higher sensitivity and specificity because they are in direct contact with the intestine and are closer to the site of intestinal inflammation. Fecal calprotectin is currently the most studied and meaningful fecal biomarker. Lactoferrin and S100A12, as novel biomarkers, have no better performance than FC in predicting the recurrence of UC.Conclusions: FC is currently the most promising predictive marker, but it lacks an accurate cut-off value. Combining patient symptoms, incorporating multiple indicators to construct a UC recurrence prediction model, and formulating individualized treatment plans for high recurrence risk patients will be the focus of UC remission management.
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Affiliation(s)
- Changchang Ge
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Lu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Zhu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Shimizu H, Ebana R, Kudo T, Sato T, Hara T, Hosoi K, Usami M, Yoshida M, Takeuchi I, Nakase H, Iwama I, Arai K, Shimizu T. Both fecal calprotectin and fecal immunochemical tests are useful in children with inflammatory bowel disease. J Gastroenterol 2022; 57:344-356. [PMID: 35165800 DOI: 10.1007/s00535-022-01856-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 01/25/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Noninvasive biomarkers of intestinal inflammation can reduce the number of endoscopies in children with inflammatory bowel disease (IBD). This study aimed to prospectively investigate the usefulness of fecal calprotectin (FCP) and fecal immunochemical test (FIT) in pediatric IBD. METHODS Patients aged 6-17 years who underwent ileocolonoscopy for established or suspected IBD were eligible for this study. Fecal samples for FCP and FIT were collected before colonoscopy. RESULTS A total of 251 samples were analyzed: 88 from ulcerative colitis (UC), 74 from Crohn's disease (CD), 75 from healthy controls (HC), and 14 from children with functional gastrointestinal disorders and normal colonoscopy (NC). At IBD diagnosis, both FCP and FIT were significantly higher in the newly diagnosed UC/CD group than in the HC/NC group (P < 0.001). The optimal cutoffs of FCP and FIT to predict IBD diagnosis were 217 mg/kg and 87 ng/mL, respectively. Patients without mucosal healing (MH) showed higher FCP and FIT than those with MH in both UC and CD (P < 0.001). The FCP increased exponentially as the endoscopic activity score increased. The optimal cutoff values of FCP and FIT for predicting MH were 161 mg/kg and 106 ng/mL for UC and 367 mg/kg and 57 ng/mL for CD, respectively. FCP showed better specificity than the FIT. Patients with CD and normal ileocolonoscopy had elevated FCP during active small intestinal inflammation. CONCLUSIONS Both FCP and FIT correlate well with endoscopic activity in pediatric patients with IBD. The FCP is a superior marker for predicting MH.
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Affiliation(s)
- Hirotaka Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
| | - Ryo Ebana
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takuro Sato
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Tomoko Hara
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Kenji Hosoi
- Department of Pediatrics, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Masaaki Usami
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Masashi Yoshida
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Ichiro Takeuchi
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Minami 1-jo Nishi 16-chome, Chuo-ku, Sapporo, 060-8543, Japan
| | - Itaru Iwama
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Katsuhiro Arai
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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Vaghari-Tabari M, Targhazeh N, Moein S, Qujeq D, Alemi F, Majidina M, Younesi S, Asemi Z, Yousefi B. From inflammatory bowel disease to colorectal cancer: what's the role of miRNAs? Cancer Cell Int 2022; 22:146. [PMID: 35410210 PMCID: PMC8996392 DOI: 10.1186/s12935-022-02557-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 03/21/2022] [Indexed: 12/27/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease with relapse and remission periods. Ulcerative colitis and Crohn's disease are two major forms of the disease. IBD imposes a lot of sufferings on the patient and has many consequences; however, the most important is the increased risk of colorectal cancer, especially in patients with Ulcerative colitis. This risk is increased with increasing the duration of disease, thus preventing the progression of IBD to cancer is very important. Therefore, it is necessary to know the details of events contributed to the progression of IBD to cancer. In recent years, the importance of miRNAs as small molecules with 20-22 nucleotides has been recognized in pathophysiology of many diseases, in which IBD and colorectal cancer have not been excluded. As a result, the effectiveness of these small molecules as therapeutic target is hopefully confirmed. This paper has reviewed the related studies and findings about the role of miRNAs in the course of events that promote the progression of IBD to colorectal carcinoma, as well as a review about the effectiveness of some of these miRNAs as therapeutic targets.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Niloufar Targhazeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Soheila Moein
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran.,Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Forough Alemi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Majidina
- Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Simin Younesi
- Schoole of Health and Biomedical Sciences, RMIT University, Melborne, VIC, Australia
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Lamb CA, Saifuddin A, Powell N, Rieder F. The Future of Precision Medicine to Predict Outcomes and Control Tissue Remodeling in Inflammatory Bowel Disease. Gastroenterology 2022; 162:1525-1542. [PMID: 34995532 PMCID: PMC8983496 DOI: 10.1053/j.gastro.2021.09.077] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/20/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease is characterized by significant interindividual heterogeneity. With a wider selection of pharmacologic and nonpharmacologic interventions available and in advanced developmental stages, a priority for the coming decade is to determine accurate methods of predicting treatment response and disease course. Precision medicine strategies will allow tailoring of preventative and therapeutic decisions to individual patient needs. In this review, we consider the future of precision medicine in inflammatory bowel disease. We discuss the critical need to extend from research focused on short-term symptomatic response to integrative multi-omic systems biology strategies to identify and validate biomarkers that underpin precision approaches. Crucially, the international community has collective responsibility to provide well-phenotyped and -curated longitudinal datasets for scientific discovery and validation. Research must also study broader aspects of the immune response, including components of the extracellular matrix, to better understand biological pathways initiating and perpetuating tissue fibrosis and longer-term disease complications.
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Affiliation(s)
- Christopher A Lamb
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Gastroenterology, Newcastle upon Tyne Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom.
| | - Aamir Saifuddin
- St Mark's Academic Institute, London North West University Hospitals National Health Service Trust, London, United Kingdom; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Nick Powell
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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46
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Wilkens R, Dolinger M, Burisch J, Maaser C. Point-of-Care Testing and Home Testing: Pragmatic Considerations for Widespread Incorporation of Stool Tests, Serum Tests, and Intestinal Ultrasound. Gastroenterology 2022; 162:1476-1492. [PMID: 34995530 DOI: 10.1053/j.gastro.2021.10.052] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 10/13/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022]
Abstract
Breaking through the biologic therapy efficacy plateau for inflammatory bowel disease requires the strategic development of personalized biomarkers in the tight control model. After risk stratification early in the disease course, targeted serial monitoring consistently to assess clinical outcomes in response to therapy allows for quick therapeutic adjustments before bowel damage can occur. Point-of-care intestinal ultrasound performed by the treating gastroenterologist is an accurate cross- sectional biomarker that monitors intestinal inflammation in real-time, enhances patient care, and increases shared understanding to help achieve common treatment goals. Combining intestinal ultrasound during a clinic visit with existing serum and stool biomarkers in a home testing setup with electronic health monitoring allows for an optimized, patient-centered personalized treatment algorithm that may improve treatment outcomes. Here, we review the current state, pragmatic considerations, and future implications of point-of-care testing and home testing for noninvasive inflammatory bowel disease monitoring in the tight control model.
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Affiliation(s)
- Rune Wilkens
- Gastrounit, Division of Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Copenhagen, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Denmark; Digestive Disease Center, Copenhagen University Hospital - Bispebjerg & Frederiksberg, Copenhagen, Denmark.
| | - Michael Dolinger
- Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Johan Burisch
- Gastrounit, Division of Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Copenhagen, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Denmark
| | - Christian Maaser
- Inflammatory Bowel Disease Outpatient Unit, Department of Geriatric Medicine, University Teaching Hospital Lueneburg, Lueneburg, Germany
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Veyrard P, Pellet G, Laharie D, Nachury M, Juillerat P, Roblin X. Efficacy of Induction Therapy With Calcineurin Inhibitors in Combination With Ustekinumab for Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol 2022; 21:1354-1355.e2. [PMID: 35307594 DOI: 10.1016/j.cgh.2022.03.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 03/09/2022] [Accepted: 03/12/2022] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis is a chronic inflammatory bowel disease. Approximately 20% of patients experience an acute severe attack during their life. In acute severe ulcerative colitis (ASUC), first-line therapy is intravenous (IV) steroids. In the absence of clinical improvement, 2 medical options can be considered: ciclosporin or infliximab.1 In ASUC, ciclosporin is commonly used as a bridging therapy for thiopurines. Pellet et al2 found that the same bridge strategy with vedolizumab was effective and can avoid colectomy. Given that an increasing number of patients with ASUC have been exposed to thiopurines, vedolizumab, and anti-tumor necrosis factor biologic therapies, newer approaches are needed in these patients, such as tofacitinib or ustekinumab. Ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, has shown efficacy in ulcerative colitis and can be given in this indication.3 In this retrospective study, we evaluate the efficacy and safety of a bridge from calcineurin inhibitor to ustekinumab in patients with ASUC.
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Affiliation(s)
- Pauline Veyrard
- Department of Gastroenterology, CHU Saint-Etienne, Clinique Mutualiste, Saint Etienne, France
| | - Gauthier Pellet
- Department of Gastroenterology and Hepatology, Centre Médico-chirurgical Magellan Hôpital Haut-Lévêque, CHU de Bordeaux, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - David Laharie
- Department of Gastroenterology and Hepatology, Centre Médico-chirurgical Magellan Hôpital Haut-Lévêque, CHU de Bordeaux, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Maria Nachury
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE, Institute for Translational Research in Inflammation, Lille, France
| | - Pascal Juillerat
- Clinic for Visceral Surgery and Medicine Inselspital, Bern University Hospital, Bern, Switzerland
| | - Xavier Roblin
- Department of Gastroenterology, CHU Saint-Etienne, Saint-Etienne, France
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Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis. J Pediatr Gastroenterol Nutr 2022; 74:72-78. [PMID: 34433783 DOI: 10.1097/mpg.0000000000003291] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
INTRODUCTION While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes. RESULTS The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a >75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year. DISCUSSION Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.
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Mori A, Mitsuyama K, Sakemi R, Yoshioka S, Fukunaga S, Kuwaki K, Yamauchi R, Araki T, Yoshimura T, Yamasaki H, Tsuruta K, Morita T, Yamasaki S, Tsuruta O, Torimura T. Evaluation of Serum Calprotectin Levels in Patients with Inflammatory Bowel Disease. Kurume Med J 2021; 66:209-215. [PMID: 34690210 DOI: 10.2739/kurumemedj.ms664009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Fecal calprotectin has been proposed as a useful biomarker of disease activity in inflammatory bowel disease (IBD). However, the role of calprotectin in systemic circulation is not well established. Thus, this study aimed to quantify serum calprotectin levels to identify a potential inflammatory marker for IBD. METHODS Ninety-eight patients with ulcerative colitis (UC) and 105 patients with Crohn's disease (CD) were prospectively enrolled and clinically scored. Ninety-two healthy, age-matched subjects served as controls. Blood samples from UC and CD patients and controls were analyzed for serum calprotectin levels and routine laboratory parameters. Disease activity was assessed by partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. RESULTS Serum calprotectin levels were higher in CD and UC patients than in controls and were higher during active disease than during inactive disease in CD but not in UC. In UC, serum calprotectin levels were correlated with C-reactive protein (CRP) but not with other laboratory parameters or disease activity. In CD, serum calprotectin levels were positively correlated with disease activity, serum CRP, and platelet count. In UC and CD, serum calprotectin and CRP levels increased during the acute phase and decreased towards remission. CONCLUSIONS Serum calprotectin is an inflammatory marker in IBD but might be more effective in evaluating patients with CD than those with UC. Further studies are needed to confirm these findings and to better determine the specific uses of serum calprotectin in routine practice.
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Affiliation(s)
- Atsushi Mori
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine.,Inflammatory Bowel Disease Center, Kurume University School of Medicine
| | - Ryosuke Sakemi
- Department of Gastroenterology, Tobata Kyoritsu Hospital
| | - Shinichiro Yoshioka
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Shuhei Fukunaga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Kotaro Kuwaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Ryosuke Yamauchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Toshihiro Araki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Tetsuhiro Yoshimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Hiroshi Yamasaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Kozo Tsuruta
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Taku Morita
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Sayo Yamasaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Osamu Tsuruta
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
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Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease. Life (Basel) 2021; 11:life11121375. [PMID: 34947906 PMCID: PMC8707558 DOI: 10.3390/life11121375] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 11/28/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Endoscopy is the gold standard to assess the condition of IBD. The problem with this procedure is that the burden and cost on the patient are high. Therefore, the identification of a reliable biomarker to replace endoscopy is desired. Biomarkers are used in various situations such as diagnosis of IBD, evaluation of disease activity, prediction of therapeutic effect, and prediction of relapse. C-reactive protein and fecal calprotectin have a lot of evidence as objective biomarkers of disease activity in IBD. The usefulness of the fecal immunochemical test, serum leucine-rich glycoprotein, and urinary prostaglandin E major metabolite have also been reported. Herein, we comprehensively review the usefulness and limitations of biomarkers that can be used in daily clinical practice regarding IBD. To date, no biomarker is sufficiently accurate to replace endoscopy; however, it is important to understand the characteristics of each biomarker and use the appropriate biomarker at the right time in daily clinical practice.
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