Epidermal Growth Factor Enemas with Oral Mesalamine for Mild-to-Moderate Left-Sided Ulcerative Colitis or Proctitis
Open accessAbstract
BACKGROUND: Epidermal growth factor (EGF) is a potent mitogenic peptide produced by salivary glands. We examined whether EGF enemas are an effective treatment for active left-sided ulcerative colitis and ulceration limited to the rectum (proctitis). METHODS: In a randomized, double-blind clinical trial conducted at Leicester Royal Infirmary, 12 patients with mild-to-moderate left-sided ulcerative colitis received daily enemas of 5 microg of EGF in 100 ml of an inert carrier and 12 received daily enemas with carrier alone for 14 days. All also began to receive 1.2 g of oral mesalamine per day or had their dose increased by 1.2 g per day. Patients were assessed clinically at 0, 2, 4, and 12 weeks and by sigmoidoscopy and biopsy at 0, 2, and 4 weeks. The primary end point was disease remission (defined by a St. Marks score of 4 or less without sigmoidoscopic evidence of inflammation) at two weeks. Secondary end points were clinically significant improvements in disease activity (defined by a decrease of more than 3 points in the St. Marks score or the ulcerative colitis disease-activity index) at two and four weeks. Analyses were performed according to the intention-to-treat principle. RESULTS: After two weeks, 10 of the 12 patients given EGF enemas were in remission, as compared with 1 of 12 in the control group (83 percent vs. 8 percent, P<0.001). At the 2-week assessment, disease-activity scores, sigmoidoscopic score, and histologic scores were all significantly better in the EGF group than in the placebo group (P<0.01 for all comparisons), and this benefit was maintained at 4 weeks and at 12 weeks. CONCLUSIONS: This study provides preliminary data suggesting that EGF enemas are an effective treatment for active left-sided ulcerative colitis.
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Cites
Podolsky, D. K. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020831 · Cited by 3,183 · see citing works
Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor
Miettinen, P. J., Berger, J. E., Meneses, J. J., Phung, Y. T., Pedersen, R. A., Werb, Z., & Derynck, R. (1995) · Nature · doi:10.1038/376337a0 · Cited by 1,038 · see citing works
Enhancement of Wound Healing by Topical Treatment with Epidermal Growth Factor
Brown, G. L., Nanney, L. B., Griffen, J., Cramer, A. B., Yancey, J. M., Curtsinger, L. J., Holtzin, L., Schultz, G. S., Jurkiewicz, M. J., & Lynch, J. B. (1989) · New England Journal of Medicine · doi:10.1056/nejm198907133210203 · Cited by 682 · see citing works
Sutherland, L. R., Martin, F., Greer, S., ROBINSON, M. G., Greenberger, N. J., Saibil, F. G., Martin, T. J., Sparr, J., Prokipchuk, E. J., & Borgen, L. A. (1987) · Gastroenterology · doi:10.1016/0016-5085(87)90621-4 · Cited by 677 · see citing works
Variation Between Observers in Describing Mucosal Appearances in Proctocolitis
Baron, J. H., Connell, A. M., & Lennard-Jones, J. E. (1964) · BMJ · doi:10.1136/bmj.1.5375.89 · Cited by 614 · see citing works
Safdi, M. A., DeMicco, M. P., Sninsky, C. A., Banks, P. L., Wruble, L. D., Deren, J. J., Koval, G., Nichols, T., Targan, S. R., Fleishman, C., et al. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)27940-7 · Cited by 322 · see citing works
Human epidermal growth factor precursor: cDNA sequence, expressionin vitroand gene organization
Bell, G. I., Fong, N. M., Stempien, M. M., et al. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.21.8427 · Cited by 319 · see citing works
Kalff, J. C., Schraut, W. H., Billiar, T. R., et al. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)70214-9 · Cited by 302 · see citing works
Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease
Wright, N. A., Poulsom, R., Stamp, G. W. H., Noorden, S. V., Sarraf, C., Elia, G., Ahnen, D. J., Jeffery, R. E., Longcroft, J. M., Pike, C. M., et al. (1993) · Gastroenterology · doi:10.1016/0016-5085(93)90830-6 · Cited by 264 · see citing works
Farrell, R. J., & Peppercorn, M. A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07499-8 · Cited by 244 · see citing works
Sutherland, L. R., May, G. R., & Shaffer, E. A. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-118-7-199304010-00009 · Cited by 233 · see citing works
Immunohistochemical localisation of urogastrone to human duodenal and submandibular glands.
Heitz, P. U., Kasper, M., Noorden, S. V., et al. (1978) · Gut · doi:10.1136/gut.19.5.408 · Cited by 201 · see citing works
Powell-Tuck, J., Day, D. W., Buckell, N. A., Wadsworth, J., & Lennard‐Jones, J. E. (1982) · Digestive Diseases and Sciences · doi:10.1007/bf01296733 · Cited by 181 · see citing works
Playford, R. J., Hanby, A. M., Gschmeissner, S., et al. (1996) · Gut · doi:10.1136/gut.39.2.262 · Cited by 159 · see citing works
Self-citationProtective effect of epidermal growth factor in an experimental model of colitis in rats
Procaccino, F., Reinshagen, M., Hoffmann, P., et al. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90055-8 · Cited by 137 · see citing works
Effect of luminal growth factor preservation on intestinal growth
Playford, R. J., Woodman, A., Vesey, D. A., Deprez, P. H., Calam, J., Watanapa, P., Williamson, R. C., & Clark, P. (1993) · The Lancet · doi:10.1016/0140-6736(93)93057-8 · Cited by 114 · see citing works
Self-citationEpidermal growth factor is digested to smaller, less active forms in acidic gastric juice
Playford, R. J., Marchbank, T., Calnan, D. P., et al. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90012-8 · Cited by 114 · see citing works
Self-citationEpidermal growth factor in necrotising enteritis
Sullivan, P., Brueton, M., Tabara, Z., et al. (1991) · The Lancet · doi:10.1016/0140-6736(91)90042-n · Cited by 113 · see citing works
Chinery, R., & Playford, R. J. (1995) · Clinical Science · doi:10.1042/cs0880401 · Cited by 112 · see citing works
Self-citationPeptides and gastrointestinal mucosal integrity.
Playford, R. J. (1995) · Gut · doi:10.1136/gut.37.5.595 · Cited by 97 · see citing works
Self-citationProphylactic Use of Epidermal Growth Factor Reduces Ischemia/Reperfusion Intestinal Damage
Berlanga, J., Prats, P. A., Remírez, D., et al. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64192-2 · Cited by 79 · see citing works
Medical therapy of ulcerative colitis
Hanauer, S. (1993) · The Lancet · doi:10.1016/0140-6736(93)92819-f · Cited by 78 · see citing works
The “Natural History” of Ulcerative Colitis
Meyers, S., & Janowitz, H. D. (1989) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-198902000-00008 · Cited by 65 · see citing works
Klotz, U. E. (2000) · European Journal of Clinical Pharmacology · doi:10.1007/s002280000163 · Cited by 51 · see citing works
Stability of recombinant human epidermal growth factor in various solutions.
ARAKI, F., Nakamura, H., NOJIMA, N., et al. (1989) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.37.404 · Cited by 41 · see citing works
Potency and stability of C terminal truncated human epidermal growth factor
Calnan, D. P., Fagbemi, A. A., Berlanga‐Acosta, J., et al. (2000) · Gut · doi:10.1136/gut.47.5.622 · Cited by 38 · see citing works
Self-citationUROGASTRONE/EPIDERMAL GROWTH FACTOR IN TREATMENT OF CONGENITAL MICROVILLOUS ATROPHY
Drumm, B. (1988) · The Lancet · doi:10.1016/s0140-6736(88)90303-0 · Cited by 33 · see citing works
Kelly, S. M., Jenner, J., Dickinson, R., et al. (1994) · Gut · doi:10.1136/gut.35.5.611 · Cited by 25 · see citing works
Increased Expression of Epidermal Growth Factor-receptor in an Experimental Model of Colitis in Rats
P. Hoffmann, M. R. (2000) · Scandinavian Journal of Gastroenterology · doi:10.1080/003655200750056655 · Cited by 24 · see citing works
Itoh, M., Imai, S., Joh, T., et al. (1992) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-199206001-00022 · Cited by 17 · see citing works
Recombinant peptides for gastrointestinal ulceration: still early days.
Playford, R. J. (1997) · Gut · doi:10.1136/gut.40.2.286 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- Podolsky DK. Inflammatory bowel dis- ease. N Engl J Med 2002;347:417-29.
- Powell-Tuck J, Day DW, Buckell NA, Wadsworth J, Lennard-Jones JE. Correla- tions between defined sigmoidoscopic ap- pearances and other measures of disease ac- tivity in ulcerative colitis. Dig Dis Sci 1982; 27:533-7.
- Berlanga J, Prats P, Remirez D, et al. Pro- phylactic use of epidermal growth factor re- duces ischemia/reperfusion intestinal dam- age. Am J Pathol 2002;16:373-9.
Cited by
Sorted by citations
Dignass, A., Lindsay, J. O., Sturm, A., Windsor, A., Colombel, J.-F., Allez, M., D'Haens, G., D'Hoore, A., Mantzaris, G., Novacek, G., et al. (2012) · Journal of Crohn's and Colitis · doi:10.1016/j.crohns.2012.09.002 · Cited by 1,548 · see citing works
Harbord, M., Eliakim, R., Bettenworth, D., Karmiris, K., Katsanos, K., Kopylov, U., Kucharzik, T., Molnár, T., Raine, T., Sebastian, S., et al. (2017) · Journal of Crohn's and Colitis · doi:10.1093/ecco-jcc/jjx009 · Cited by 1,180 · see citing works
Epithelial restitution and wound healing in inflammatory bowel disease
Sturm, A., & Dignass, A. U. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.348 · Cited by 334 · see citing works
Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis
Higgins, P. D. R., Schwartz, M., Mapili, J., Krokos, I., Leung, J., & Zimmermann, E. M. (2005) · Gut · doi:10.1136/gut.2004.056358 · Cited by 244 · see citing works
The Manitoba IBD Index: Evidence for a New and Simple Indicator of IBD Activity
Clara, I., Lix, L. M., Walker, J. R., Graff, L. A., Miller, N., Rogala, L., Rawsthorne, P., & Bernstein, C. N. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.197 · Cited by 119 · see citing works
Resolution of inflammation in inflammatory bowel disease
Rogler, G. (2017) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(17)30031-6 · Cited by 79 · see citing works
Wang, Y., Shi, C., Lu, Y., Poulin, E. J., Franklin, J. L., & Coffey, R. J. (2015) · The American Journal of Pathology · doi:10.1016/j.ajpath.2014.12.014 · Cited by 26 · see citing works
- Authors
- Sinha, A., Nightingale, J. M. D., West, K. P., Berlanga-Acosta, J., & Playford, R. J.
- Affiliations
- Leicester Royal Infirmary (GB)
- Hammersmith Hospital (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-07-24
- Volume
- 349
- Issue
- 4
- Pages
- 350-357
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2099599782
- Cited by
- 303
- References
- 31
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 9 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 14 · 2012: 18
- FWCI
- 14.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Health Sciences › Medicine › Surgery › Anorectal Disease Treatments and Outcomes
- Keywords
- epidermal growth factor, ulcerative colitis, proctitis, remission, disease activity
- MeSH terms
- Administration, Oral, Adult, Anti-Inflammatory Agents, Non-Steroidal, Colitis, Ulcerative, Double-Blind Method, Drug Therapy, Combination, Enema, Epidermal Growth Factor, Female, Humans, Male, Middle Aged, Proctitis, Remission Induction, Mesalamine
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