Azathioprine and 6-Mercaptopurine in Crohn Disease

Pearson, David; May, Gary R.; Fick, Gordon H.; Sutherland, Lloyd R.

doi:10.7326/0003-4819-123-2-199507150-00009

Cited by 911 publications

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“…In our series, the probability of remission with corticosteroid withdrawal after 6 and 12 months of remission in patients with active disease at the initiation of the drug was 46% and 79%, respectively, a rate similar to the one reported with AZA/MP. 1,[37][38][39] In patients on TG maintenance therapy, the probability of relapse at 6 and 12 months was 29% and 53%, respectively. The number of patients available for the evaluation of the TG maintenance effect is small (n ¼ 28), and the followup period is still short (median 5 months).…”

Section: Discussionmentioning

confidence: 99%

“…Among 21 of them, remission was achieved without corticosteroids or infliximab during the follow-up period (median duration 7 months, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The probability of remission without corticosteroids or infliximab was 46% (95% CI, 37-55%) and 79% (95% CI, 70-88%) at 6 and 12 months, respectively ( Figure 2).…”

Section: Efficacymentioning

confidence: 99%

“…Approximately 40% of inflammatory bowel diseases patients fail to achieve a complete clinical response under AZA/MP. 1 One of the mechanisms may be the preferential overproduction of 6-methylmercaptopurine ribonucleotides (6-MMPR) upon dose escalation through high inherited thiopurine methyl transferase (TPMT) activity. 12 TPMT is, with xanthine oxydase (XO) and hypoxanthine phosphoribosyl transferase (HPRT), one of the three enzymes involved in the metabolism of AZA/MP (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine

Bonaz

Boitard

Marteau

et al. 2003

Aliment Pharmacol Ther

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Summary Background: Tioguanine (TG) is an antimetabolite which may be regarded as an alternative to azathioprine (AZA)/mercaptopurine (MP) in patients with inflammatory bowel diseases. Aims : To evaluate the tolerance and efficacy of TG in patients with Crohn's disease, intolerant or resistant to AZA/MP. Methods : An open prospective study was made on Crohn's disease patients treated with TG. Intolerance to AZA/MP was defined as a reaction occurring within 1 month after introduction of AZA/MP, including pancreatitis, abdominal pain, fever, arthralgia, myalgia, cutaneous rash, fatigue, alopecia, hepatitis and digestive intolerance. Resistance to AZA/MP was defined as the persistence of activity after at least 3 months of AZA/MP therapy. Results : Forty‐nine Crohn's disease patients (36 women, 13 men; intolerance: n = 39; resistance: n= 10) were treated with TG (20 mg/day). Clinical pancreatitis did not recur under TG. Five patients (10%) had to stop TG due to intolerant reactions observed 13–21 days after TG was started. No haematological side‐effects were observed under TG. The probability of clinical remission without corticosteroids or infliximab at 6 and 12 months was 46% and 79%, respectively, in the 40 patients with active disease at baseline. The probability of clinical relapse during maintenance TG therapy at 6 and 12 months was 29% and 53%, respectively, in the 28 patients in remission at baseline or who had achieved remission on TG. Conclusions : TG is a possible alternative treatment in Crohn's disease patients, intolerant (especially for pancreatitis) or resistant to AZA/MP.

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Section: Discussionmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine

Bonaz

Boitard

Marteau

et al. 2003

Aliment Pharmacol Ther

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“…A meta-analysis by Pearson et al [57] reported an odds ratio of 3.09 for response to therapy over placebo. In the more recent meta-analyses conducted for the Cochrane database, a pooled effi cacy of 54% and 71% for induction and maintenance of CD remission was reported for AZA [58,59].…”

Section: Thiopurinesmentioning

confidence: 99%

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

2017

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Tumor necrosis factor (TNF)-α inhibitors and thiopurines are among the most important classes of medications utilized in the clinical management of Crohn's disease and ulcerative colitis. A signifi cant proportion of patients loses response to these agents or develops adverse eff ects during the course of the treatment. Monitoring of drug levels and anti-drug antibodies (for TNF-α inhibitors) and metabolite levels (for thiopurines) can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients. Th is review summarizes the current knowledge on the clinical implications of therapeutic drug monitoring in infl ammatory bowel disease patients treated with TNF-α inhibitors and thiopurines.

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“…The immunosuppressants, azathioprine (AZA) and 6‐mercaptopurine (6‐MP), are used as a second‐line therapy in almost 60% of patients with IBD to induce and maintain remission 1, 2, 3, 4, 5, 6. The recommended dose of AZA is up to 2.5 mg/kg and that of 6‐MP is 1–1.5 mg/kg/day.…”

Section: Introductionmentioning

confidence: 99%

Thiopurine metabolite level and toxicity in Indians with inflammatory bowel disease

et al. 2017

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Background and AimA lower dose requirement and higher toxicity of thiopurine is reported in Asian patients with inflammatory bowel disease (IBD) as compared with Caucasian patients. These reports are based on thiopurine methyltransferase measurement studies rather than metabolite estimation.We studied the utility of thiopurine metabolite estimation in Indian patients with IBD and compared dose and toxicity with Asian and Caucasian patients.MethodsIn this prospective study, 6‐thioguanine nucleotide (6‐TGN) and 6‐methylmercaptopurine levels were determined by HPLC in 76 IBD patients treated with thiopurines. The levels were correlated with dose, disease activity, and toxicity. The dose‐related metabolite levels and toxicity were compared with Caucasian and Asian patients reported in literature.ResultsOf the 76 patients (32 women, mean age: 35.9 [SD: 14.54] years, 36 Crohn's disease and 40 ulcerative colitis), 1 non‐compliant patient had undetectable level of metabolites. Of the 75 patients, 21(28%) had therapeutic level of 6‐TGN, 37(49%) had subtherapeutic level and 17(23%) had supratherapeutic level. The 6‐methylmercaptopurine levels ranged up to 4971 pmol/8 × 108 red blood cells. Six (8%) patients showed toxicity. Thiopurine dose was optimized in 20 (26.31%) patients. Dose‐based metabolite levels were comparable to Asian and Caucasian patients. The toxicity (8%) observed in our patients was less than that reported (12–39%).ConclusionHalf of the patients in this study had low and a quarter had high 6‐TGN levels. One‐fourth of the patients needed dose modification. The dose‐based metabolite levels were comparable and the toxicity was less than that reported in Asian and Caucasian patients.

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Azathioprine and 6-Mercaptopurine in Crohn Disease

Abstract: Azathioprine and 6-mercaptopurine are effective in treating active Crohn disease and in maintaining remission. Cumulative dose was an important factor in predicting response. Adverse effects were more common among patients receiving therapy.

Cited by 911 publications

References 0 publications

Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine

Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

Thiopurine metabolite level and toxicity in Indians with inflammatory bowel disease

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