Introduction of 6-Mercaptopurine in Crohn's Disease Patients During the Perioperative Period: A Preliminary Evaluation of Recurrence of Disease

Kader, Howard A.; Raynor, Stephen C.; Young, R L; Kaufman, Stuart S.; Vanderhoof, Jon A.; Ruby, Elizabeth I.; Mack, David R.

doi:10.1097/00005176-199707000-00016

Cited by 30 publications

(8 citation statements)

References 22 publications

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“…Another pediatric study showed a clinical response in about 70% of children with CD; more than half were able to discontinue prednisone completely during the first 6 months of 6-MP use (175). Recurrence of disease after surgery may be prevented with 6-MP, as was shown in a small, uncontrolled study by Kader et al (176).…”

Section: Experience In Childrenmentioning

confidence: 86%

Treatment of Inflammatory Bowel Disease in Childhood: Best Available Evidence

Escher

Taminiau

Nieuwenhuis

et al. 2003

Inflammatory Bowel Diseases

113

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The physician treating children with inflammatory bowel disease is confronted with a number of specific problems, one of them being the lack of randomized, controlled drug trials in children. In this review, the role of nutritional therapy is discussed with a focus on primary treatment, especially for children with Crohn's disease. Then, the available medical therapies are highlighted, reviewing the evidence of effectiveness and side effects in children, as compared with what is known in adults. Nutritional therapy has proven to be effective in inducing and maintaining remission in Crohn's disease while promoting linear growth. Conventional treatment consists of aminosalicylates and corticosteroids, whereas the early introduction of immunosuppressives (such as azathioprine or 6-mercaptopurine) is advocated as maintenance treatment. If these drugs are not tolerated or are ineffective, methotrexate may serve as an alternative in Crohn's disease. Cyclosporine is an effective rescue therapy in severe ulcerative colitis, but only will postpone surgery. A novel strategy to treat Crohn's disease is offered by infliximab, a monoclonal antibody to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. Based on the best-available evidence, suggested usage is provided for separate drugs with respect to dosage and monitoring of side effects in children.

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Section: Experience In Childrenmentioning

confidence: 86%

Treatment of Inflammatory Bowel Disease in Childhood: Best Available Evidence

Escher

Taminiau

Nieuwenhuis

et al. 2003

Inflammatory Bowel Diseases

113

View full text Add to dashboard Cite

show abstract

“…Azathioprine and MP in combination with other immunosuppressants like cyclosporine, tacrolimus, methotrexate, thalidomide or infliximab have proven efficacy in CD perianal fistulas with prolonged fistula closure in 30–40% of cases 16–19 . Moreover, both thiopurines help to prevent the recurrence of CD after surgery, especially in high risk patients, with a NNT of four in 2 years to prevent one clinical relapse 20–23 …”

Section: Efficacymentioning

confidence: 99%

Review article: thiopurines in inflammatory bowel disease

Derijks

Gilissen

Hooymans

et al. 2006

Aliment Pharmacol Ther

146

139

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“…They are frequently prescribed for patients in whom first‐line therapy fails, in particular those who are steroid‐dependent or who do not have a response to systematic corticosteroids 5, 6 . Both AZA and 6‐MP have proven their efficacy for the induction of remission in active Crohn’s disease, 7, 8 for maintaining remission and sparing steroids in quiescent steroid‐dependent Crohn’s disease, 9, 10 or for preventing recurrence after surgery in Crohn’s disease 11–15 . For use in ulcerative colitis, efficacy has been proven for maintenance therapy, but only as alternative treatment 16 …”

Section: Introductionmentioning

confidence: 99%

Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease

Chouchana

Narjoz

Beaune

et al. 2011

Aliment Pharmacol Ther

149

142

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Aliment Pharmacol Ther 2012; 35: 15–36 Summary Background Thiopurines represent an effective and widely prescribed therapy in inflammatory bowel disease (IBD). Concerns about toxicity, mainly resulting from a wide inter‐individual variability in thiopurine metabolism, restrict their use. Optimal thiopurine dosing is challenging for preventing adverse drug reactions and improving clinical response. Aim To review efficacy and toxicity of thiopurines in IBD. To provide pharmacogenetic‐based therapeutic recommendations. Methods We conducted a query on PubMed database using ‘inflammatory bowel disease’, ‘thiopurine’, ‘azathioprine’, ‘6‐mercaptopurine’, ‘TPMT’, ‘pharmacogenetics’, ‘TDM’, and selected relevant articles, especially clinical studies. Results Thiopurine metabolism – key enzyme: thiopurine S‐methyltransferase (TPMT) – modulates clinical response, as it results in production of the pharmacologically active and toxic metabolites, the thioguanine nucleotides (6‐TGN). Adjusting dosage according to TPMT status and/or metabolite blood levels is recommended for optimising thiopurine therapy (e.g. improving response rate up to 30% or decreasing haematological adverse events of 25%). Other enzymes or transporters of interest, as inosine triphosphatase (ITPase), glutathione S‐transferase (GST), xanthine oxidase (XO), aldehyde oxidase (AOX), methylene tetrahydrofolate reductase (MTHFR) and ATP‐binding cassette sub‐family C member 4 (ABCC4) are reviewed and discussed for clinical relevance. Conclusions Based on the literature data, we provide a therapeutic algorithm for thiopurines therapy with starting dose recommendations depending on TPMT status and thereafter dose adjustments according to five metabolite profiles identified with therapeutic drug monitoring (TDM). This algorithm allows a dosage individualisation to optimise the management of patients under thiopurine. Furthermore, identification of new pharmacogenetic biomarkers is promising for ensuring maximal therapeutic response to thiopurines with a minimisation of the risk for adverse events.

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Introduction of 6-Mercaptopurine in Crohn's Disease Patients During the Perioperative Period: A Preliminary Evaluation of Recurrence of Disease

Cited by 30 publications

References 22 publications

Treatment of Inflammatory Bowel Disease in Childhood: Best Available Evidence

Treatment of Inflammatory Bowel Disease in Childhood: Best Available Evidence

Review article: thiopurines in inflammatory bowel disease

Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease

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