TY - JOUR
T1 - DEVELOPMENT OF ANTIFIBROTIC THERAPY FOR STRICTURING CROHN’S DISEASE
T2 - LESSONS FROM RANDOMIZED TRIALS IN OTHER FIBROTIC DISEASES
AU - Antifibrotic Research (STAR) Consortium
AU - Lin, Si Nan
AU - Mao, Ren
AU - Qian, Chenchen
AU - Bettenworth, Dominik
AU - Wang, Jie
AU - Li, Jiannan
AU - Bruining, David H.
AU - Jairath, Vipul
AU - Feagan, Brian G.
AU - Chen, Min Hu
AU - Therapy, Stenosis
AU - Rieder, Florian
N1 - Funding Information:
This work was supported by the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium (No. 3081 to F.R.), the Crohn’s and Colitis Foundation (No. 569125 to F.R.), the National Institutes of Health (NIDDK K08DK110415 and R01DK123233 to F.R.), the Cleveland Clinic through the LabCo program to F.R., and the National Science Foundation of China (No. 81970483 to R.M.).
Funding Information:
Ltd., Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann-La Roche Ltd., Gilead Sciences Inc., GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc., Receptos Inc./Celgene International, Sanofi, Santarus Inc., Takeda Development Center Americas Inc., Tillotts Pharma AG, and UCB, consulting fees from Abbott/ AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc., Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., and Zyngenia, and speaker’s bureau fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novo-nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; and is the Senior Scientific Officer of Alimentiv Inc. F.R. is a consultant to Agomab, Allergan, AbbVie, Boehringer-Ingelheim, Celgene, Cowen, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Index Pharma, Jannsen, Koutif, Metacrine, Morphic, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Takeda, Techlab, Thetis, and UCB and receives funding from the Crohn’s and Colitis Foundation of America, the Helmsley Charitable Trust, Kenneth Rainin Foundation, and the National Institutes of Health. None of the other authors has any conflicts of interest, financial or otherwise, to disclose.
Funding Information:
D.B. is on the advisory board of or is a consultant for AbbVie, Amgen, Arena, BNG Service, Celltrion, Dr. Falk Foundation, Ferring, Galapagos Janssen-Cilag, Medical Tribune, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Thieme, Tillotts Pharma, and Vifor. V.J. has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Alimentiv Inc., Topivert, and Celltrion and speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer. B.G.F. has received grant/research support from AbbVie Inc., Amgen Inc., AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals
Publisher Copyright:
© 2022 the American Physiological Society.
PY - 2022/4
Y1 - 2022/4
N2 - Intestinal fibrosis is considered an inevitable complication of Crohn’s disease(CD)thatresultsinsymptomsofobstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.
AB - Intestinal fibrosis is considered an inevitable complication of Crohn’s disease(CD)thatresultsinsymptomsofobstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.
KW - Clinical trials
KW - Crohn’s disease
KW - End point
KW - Stricture
UR - http://www.scopus.com/inward/record.url?scp=85122481010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122481010&partnerID=8YFLogxK
U2 - 10.1152/physrev.00005.2021
DO - 10.1152/physrev.00005.2021
M3 - Review article
C2 - 34569264
AN - SCOPUS:85122481010
VL - 102
SP - 605
EP - 652
JO - Physiological Reviews
JF - Physiological Reviews
SN - 0031-9333
IS - 2
ER -