TY - JOUR
T1 - Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease
T2 - A Systematic Review
AU - Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium
AU - Steiner, Calen A.
AU - Berinstein, Jeffrey A.
AU - Louissaint, Jeremy
AU - Higgins, Peter D.R.
AU - Spence, Jason R.
AU - Shannon, Carol
AU - Lu, Cathy
AU - Stidham, Ryan W.
AU - Fletcher, Joel G.
AU - Bruining, David H.
AU - Feagan, Brian G.
AU - Jairath, Vipul
AU - Baker, Mark E.
AU - Bettenworth, Dominik
AU - Rieder, Florian
N1 - Funding Information:
Funding Calen A. Steiner is supported by a grant from the National Institutes of Health (T32 DK 094775). Peter D. R. Higgins is supported by grants from the National Institutes of Health (R01 DK 118154), and the U-M Center for the Discovery of New Medicines. Ryan W. Stidham is supported by grants from the National Institutes of Health (R01DK124779) and the Crohn's and Colitis Foundation, and has investigator-initiated research support through AbbVie. Joel G. Fletcher receives funding support from grants from Siemens Healthineers, the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research Consortium, Takeda Pharmaceuticals, and National Institutes of Health (R01 EB017095, U24 EB28936, R01 DK120559); funds from all grants are paid to Mayo Clinic. Florian Rieder is supported by grants from the National Institutes of Health (K08DK110415 and R01DK123233), the Crohn's and Colitis Foundation, the Rainin Foundation, and the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium. Conflicts of interest These authors disclose the following: Peter D.R. Higgins has received consulting fees from AbbVie, Amgen, Genentech, JBR Pharma, and Lycera. Cathy Lu has received consulting fees from AbbVie, Janssen, and Takeda; and speaker's fees from AbbVie and Janssen. Ryan W. Stidham is on the advisory board or served as a consultant for AbbVie, Janssen, Takeda, Corrona, Exact Sciences, and Gilead. Joel G. Fletcher has served as a consultant for Takeda Pharmaceuticals, Medtronic, Janssen, Pfizer, Glaxo Smith Kline, and Boehringer-Ingelheim, with fees paid to his institution. David H. Bruining has received consulting fees form Medtronic; and research support from Medtronic and Takeda. Brian G. Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGeniX, and Wyeth Pharmaceuticals; consulting fees from Millennium Pharmaceuticals, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma GmbH Pharma, AbbVie, AstraZeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novo Nordisk, GlaxoSmithKline, ActoGeniX, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma, and Sigmoid Pharma; and speaker's bureau fees from UCB, AbbVie, and Johnson & Johnson/Janssen. Vipul Jairath has received consulting fees from AbbVie, Alimentic (formerly Robarts Clinical Trials), Arena pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pendopharm, Pfizer, Roche, Sandoz, Takeda, and Topivert; and speaker's fees from, Abbvie, Ferring, Janssen, Pfizer, Shire, and Takeda. Mark E. Baker receives no direct support; Cleveland Clinic receives support for him from Siemens Healthineers in the form of salary, software, and hardware for the investigation of reduced exposure in CT Enterography as well as from the Leona and Harry Helmsley Charitable Trust and from Pfizer grants through the Stenosis Therapy and Anti-Fibrotic Research Consortium in the form of salary. Dominik Bettenworth has served on the advisory board or consultant for Amgen, AbbVie, Celltrion, Dr. Falk Foundation, Ferring, Galapagos, Janssen, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts Pharma, and Vifor. Florian Rieder has served on the advisory board or as a consultant to Agomab, Allergan, AbbVie, Boehringer Ingelheim, Celgene/BMS, CDISC, Cowen, Galmed, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Index Pharma, Jannsen, Koutif, Mestag, Metacrine, Morphic, Organovo, Origo, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Surmodics, Surrozen, Takeda, Techlab, Theravance, Thetis, UCB, Ysios, and 89Bio. The remaining authors disclose no conflicts.
Funding Information:
Funding Calen A. Steiner is supported by a grant from the National Institutes of Health (T32 DK 094775). Peter D. R. Higgins is supported by grants from the National Institutes of Health (R01 DK 118154), and the U-M Center for the Discovery of New Medicines. Ryan W. Stidham is supported by grants from the National Institutes of Health (R01DK124779) and the Crohn’s and Colitis Foundation, and has investigator-initiated research support through AbbVie. Joel G. Fletcher receives funding support from grants from Siemens Healthineers , the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research Consortium, Takeda Pharmaceuticals, and National Institutes of Health (R01 EB017095, U24 EB28936, R01 DK120559); funds from all grants are paid to Mayo Clinic. Florian Rieder is supported by grants from the National Institutes of Health (K08DK110415 and R01DK123233), the Crohn’s and Colitis Foundation, the Rainin Foundation, and the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium.
Publisher Copyright:
© 2022 AGA Institute
PY - 2022/4
Y1 - 2022/4
N2 - Background and Aims: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. Methods: We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). Results: Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. Conclusions: There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
AB - Background and Aims: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. Methods: We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). Results: Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. Conclusions: There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
KW - Biomarker
KW - Crohn's Disease
KW - Fibrosis
KW - Fibrostenosis
KW - IBD
KW - Inflammatory Bowel Disease
KW - Stenosis
KW - Stricture
UR - http://www.scopus.com/inward/record.url?scp=85114327903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114327903&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.05.054
DO - 10.1016/j.cgh.2021.05.054
M3 - Article
C2 - 34089850
AN - SCOPUS:85114327903
SN - 1542-3565
VL - 20
SP - 817-846.e10
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 4
ER -