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Simple water‐based tacrolimus enemas for refractory proctitis

BACKGROUND AND AIMS: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal syste...

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Autores principales: Fehily, Sasha R., Martin, Felicity C., Kamm, Michael A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Publishing Asia Pty Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411644/
https://www.ncbi.nlm.nih.gov/pubmed/32782938
http://dx.doi.org/10.1002/jgh3.12280
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author Fehily, Sasha R.
Martin, Felicity C.
Kamm, Michael A.
author_facet Fehily, Sasha R.
Martin, Felicity C.
Kamm, Michael A.
author_sort Fehily, Sasha R.
collection PubMed
description BACKGROUND AND AIMS: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water‐based enema formulation. METHODS: Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end‐point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end‐points included endoscopic remission, clinical response, stool frequency, and rectal bleeding. RESULTS: Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1–4 mg tacrolimus daily and 1–3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3–204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; P = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C‐reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare. CONCLUSIONS: Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease‐related refractory proctitis.
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spelling pubmed-74116442020-08-10 Simple water‐based tacrolimus enemas for refractory proctitis Fehily, Sasha R. Martin, Felicity C. Kamm, Michael A. JGH Open Leading Articles BACKGROUND AND AIMS: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water‐based enema formulation. METHODS: Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end‐point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end‐points included endoscopic remission, clinical response, stool frequency, and rectal bleeding. RESULTS: Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1–4 mg tacrolimus daily and 1–3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3–204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; P = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C‐reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare. CONCLUSIONS: Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease‐related refractory proctitis. Wiley Publishing Asia Pty Ltd 2019-11-14 /pmc/articles/PMC7411644/ /pubmed/32782938 http://dx.doi.org/10.1002/jgh3.12280 Text en © 2019 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Leading Articles
Fehily, Sasha R.
Martin, Felicity C.
Kamm, Michael A.
Simple water‐based tacrolimus enemas for refractory proctitis
title Simple water‐based tacrolimus enemas for refractory proctitis
title_full Simple water‐based tacrolimus enemas for refractory proctitis
title_fullStr Simple water‐based tacrolimus enemas for refractory proctitis
title_full_unstemmed Simple water‐based tacrolimus enemas for refractory proctitis
title_short Simple water‐based tacrolimus enemas for refractory proctitis
title_sort simple water‐based tacrolimus enemas for refractory proctitis
topic Leading Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411644/
https://www.ncbi.nlm.nih.gov/pubmed/32782938
http://dx.doi.org/10.1002/jgh3.12280
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