Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method

Murphy, Seamus; Wang, L.; Anderson, Lesley A.; Steinlauf, Adam F.; Present, Daniel H.; Mechanick, Jeffrey I.

doi:10.1111/j.1365-2036.2009.04136.x

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…Although 5-ASA therapy is well tolerated and effective in patients with mild to moderate inflammation, many patients are refractory to this therapy or undergo relapse when 5-ASA is used to maintain remission (24). For this reason, and because of the undesirability of long-term corticosteroid use as the next level of UC therapy (46), there is strong interest in understanding the basis for variable outcomes with 5-ASA.…”

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confidence: 99%

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

Ramírez-Alcántara

Montrose

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ramírez-Alcántara V, Montrose MH. Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2. Am J Physiol Gastrointest Liver Physiol 306: G1002-G1010, 2014. First published April 17, 2014 doi:10.1152/ajpgi.00389.2013.-Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment for ulcerative colitis, but variable patient response to this therapy is observed. Inflammation can affect therapeutic outcomes by regulating the expression and activity of drug-metabolizing enzymes; its effect on 5-ASA metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is not firmly established. We examined if inflammation affects the capacity for colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5-ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable with Km (5-ASA) ϭ 5.8 M. A mouse model of acute dextran sulfate sodium (DSS) colitis caused pronounced inflammation in central and distal colon, and modest inflammation of proximal colon, defined by myeloperoxidase activity and histology. DSS colitis reduced capacity for 5-ASA metabolism in central and distal colon segments by 52 and 51%, respectively. Use of selective substrates of NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA metabolism in normal and colitis conditions. Western blot and real-time RT-PCR identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA ratio after DSS. In conclusion, an acute colonic inflammation impairs the expression and function of mNAT2 enzyme, thereby diminishing the capacity for 5-ASA metabolism by colonic mucosa. drug metabolism; fluorescence; dextran sulfate sodium; myeloperoxidase; kinetics; enzymatic assay; inflammatory bowel disease; enzyme isoform THE TWO MAJOR INFLAMMATORY bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease, afflict 1.4 million individuals in the United States (USA) and 2.2 million in Europe (42). To induce and maintain mucosal healing of the colonic mucosa, the major goal of UC therapy is to reduce or eliminate colonic inflammation. For mild to moderate inflammation, therapy based on the nonsteroidal anti-inflammatory compound 5-aminosalicylic acid (5-ASA) is frequently prescribed. In information compiled by the National Institutes of Health from the 2004 Verispan database of prescriptions filled at retail pharmacies in the USA, 5-ASA or its prodrugs accounted for 44% of Crohn's disease prescriptions and 81% of UC prescriptions (23). It is not well understood how 5-ASA induces its antiinflammatory effect on colonic mucosa, but multiple mechanisms have been proposed, including inhibition of intestinal macrophage chemotaxis (47), inhibition of proinflammatory cytokine release (25), inhibition of cyclooxygenase and prostaglandin pathways (28), inhibition of nuclear fa...

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confidence: 99%

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

Ramírez-Alcántara

Montrose

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…If disease relapse is thought likely, it is suggested to increase exogenous corticosteroids around the time of delivery, with a subsequent slow withdrawal of the additional dose. The slow withdrawal period has been described in non‐pregnant patients as a method of reducing disease reactivation …”

Section: Maternal Exposure To Exogenous Corticosteroidsmentioning

confidence: 99%

Maternal, fetal, and neonatal outcomes associated with long‐term use of corticosteroids during pregnancy

AlSaad

Lindow

Lee

et al. 2019

The Obstetric & Gynaecologis

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“…Mainly arthralgia (joint pain without inflammation) and arthritis (joint pain with objective signs of inflammation) need to be distinguished. Arthralgia in IBD patients can be caused by the introduction of thiopurines 128,129 or by the withdrawal of corticosteroids 130 .…”

Section: Expert Commentarymentioning

confidence: 99%

Management of patients with inflammatory bowel disease and spondyloarthritis

Pouillon

Bossuyt

Vanderstukken

et al. 2017

Expert Review of Clinical Pharmacology

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More than half of the patients with inflammatory bowel disease (IBD) experience at least one extra-intestinal manifestation (EIM). The most common EIM in patients with IBD is spondyloarthritis (SpA). Microscopic intestinal inflammation is documented in almost 50% of the patients with SpA. Areas covered: We give an overview of the classification, the epidemiology and the diagnosis of IBD and SpA. The treatment goals, the pharmacologic management options and the available treatment guidelines in IBD patients with SpA are discussed. Expert commentary: The coexistence of IBD and SpA generates challenges and opportunities for both the gastroenterologist and the rheumatologist. The potential of drugs with a gut-specific mode of action in the treatment of IBD-related arthritis warrants further exploration.

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Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method

Abstract: SUMMARY Background

Cited by 6 publications

References 40 publications

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

Maternal, fetal, and neonatal outcomes associated with long‐term use of corticosteroids during pregnancy

Management of patients with inflammatory bowel disease and spondyloarthritis

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