Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience.

Connell, William; Kamm, MA; Ritchie, Jean K.; Lennard-Jones, J E

doi:10.1136/gut.34.8.1081

Cited by 469 publications

(324 citation statements)

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“…Myelosuppression is the most feared consequence and occurs in 1.4^5% of cases. 11,13,14 Some cases of mild myelosuppression can be resolved by dose reduction but more severe cases require immediate withdrawal. The most common adverse events are allergic reactions (2.3%), 11 which include a febrile myalgic reaction usually seen in the ¢rst two weeks of commencing the drugs.…”

Section: Thiopurine Toxicitymentioning

confidence: 99%

Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?

et al. 2004

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Thiopurines [azathioprine (AZA), 6-mercaptopurine (6-MP) and thioguanine (6-TG)] have a well-established role as immunosuppressive agents in a variety of chronic inflammatory conditions, haematological neoplasia and in transplant rejection. Despite good overall clinical response rates, particularly when used as steroid sparing agents, adverse effects are a limiting problem leading to withdrawal in up to a quarter of patients. Severe myelosuppression is the most serious toxicity occurring early or occasionally later during treatment.An understanding of the competing pathways involved in the metabolism of thiopurines has important implications for predicting some of the more severe toxicity seen with these drugs. Thiopurine methyl transferase (TPMT) is an enzyme catalysing the methylation of 6-MP, competing with xanthine oxidase (XO) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) to determine the amount of 6-MP metabolised to cytotoxic thioguanine nucleotides. Allelic polymorphisms in the TPMT gene predict the activity of the enzyme such that 1 in 10 of the population are heterozygous and have approximately 50% of normal activity, whilst 1 in 300 are completely deficient. As a result, these individuals are at high risk of severe myelosuppression. Conversely, individuals with very high levels of TPMT activity are hyper-methylators in whom clinical response is less likely.Prior knowledge of TPMT status avoids exposure of individuals with zero TPMT to potentially fatal treatment with AZA or 6-MP and provides one of the best examples of predictive pharmacogenetics in therapeutics. This article reviews literature on the role of TPMT measurement prior to treatment with thiopurines and provides some guidance to the use of TPMT as a guide to tailoring thiopurine therapy.

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Section: Thiopurine Toxicitymentioning

confidence: 99%

Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?

et al. 2004

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“…Maintenance therapy with in iximab, adalimumab, and certolizumab pegol is e ective (grade A). In iximab monotherapy and in iximab combined with azathioprine are more e ective than azathio-(e.g., leukopenia and thrombocytopenia) (214,215) . Pancreatitis, typically presenting several weeks a er initiating therapy, occurs in approximately 3 -15 % of patients and recurs with re-introduction of either azathioprine or mercaptopurine (17) .…”

Section: Maintenance Therapymentioning

confidence: 99%

Management of Crohn's Disease in Adults

2009

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Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifi cally valid research, derived from extensive review of published literature. When data that will withstand objective scrutiny are not available, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be fl exible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are infl exible and rarely violated. Given the wide range of choices in any health-care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. Expert opinion is solicited from the outset for the document. The quality of evidence upon which a specifi c recommendation is based is as follows: Grade A: Homogeneous evidence from multiple well-designed randomized (therapeutic) or cohort (descriptive) controlled trials, each involving a number of participants to be of suffi cient statistical power. Grade B: Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case -control analytic studies, or well-designed meta-analysis. Grade C: Evidence based on clinical experience, descriptive studies, or reports of expert committees. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fi elds. The fi nal recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientifi c developments at a later time.

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“…Uncertainty regarding the risk for neutropenia deters some physicians from using AZA at effective doses and longer treatment with it. Experience abroad has shown that AZA can be safely used in treatment of CD and UC [25][26][27] . Recently, thiopurine methyltransferase (TPMT) and its genotype have been applied in predicting the myelotoxicity and reducing the incidence of leucopenia in Europe and North America [28][29][30] .…”

Section: Discussionmentioning

confidence: 99%

Quality of care for patients with inflammatory bowel disease in East China

Zhu¹,

Cao²,

Si³

2008

WJG

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received immunomodulatory agents, and more than half of the 8 patients received a suboptimal dose of azathiopurine with no attempt to increase its dosage. CONCLUSION:The quality of care for IBD patients can be further improved. A suboptimal dose of aminosalicylate is used in treatment of patients with CD, especially in those with small intestine involved only. Topical mesalazine is inadequately used in patients with distal or left-sided colitis. Oral or intravenous steroid therapy is not used in some patients with severe IBD. Use of immunomodulatory medication is limited. Larger prospective studies are needed to investigate the quality of care for patients with IBD to establish our own evidence-based guidelines. INTRODUCTIONInflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder of the gastrointestinal tract. The prevalence of IBD is about 1.0/1000 in Western countries [1] . No large scale epidemiological investigation is available on the incidence and prevalence of IBD in China so far, but the diagnosed IBD in China has increased obviously in the past ten years [2] .A number of national and international practice guidelines for management of inflammatory bowel disease are available [3][4][5] . However, the essentials in a step-up treatment have not changed significantly. These practice guidelines are means of bringing evidence-based medicine into full play to improve IBD patient care. However, such [2] . This study was to investigate the impact of such guidelines and the quality of care for a hospital based cohort of patients with IBD from East China. MATERIALS AND METHODS SubjectsIBD patients admitted to Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, between June 2000 and June 2006, were consecutively enrolled in this study. The diagnosis of IBD was confirmed by the criteria established by Chinese Society of Gastroenterology [6] in 2000 and the guidelines issued by the Clinical Services Committee of the British Society of Gastroenterology (BSG) [3] in 2004. The patients not under the care of a gastroenterologist were excluded. Data collectionA retrospective review was performed. Clinical data on demographic information, clinical characteristics of IBD patients, as well as endoscopic, radiologic, surgical and pathological records, confirmed diagnoses, duration and severity of disease, medical therapy, were collected from the inpatient and follow-up clinic visit records and input into an IBD database. Medical therapy included use of oral aminosalicylate, topical therapy, corticosteroid agents, and use of immunomodulatory agents at admission and outpatient clinic visit. Statistical analysisVariables were expressed as mean, while categorical data such as proportion of patients receiving particular therapies and dose of medications were expressed as percentage. Association of patient gender, age, location and severity of disease with suboptimal therapy was analyzed by χ 2 test. P < 0.05 was considered statistically significant. All ...

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Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience.

Cited by 469 publications

References 30 publications

Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?

Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?

Management of Crohn's Disease in Adults

Quality of care for patients with inflammatory bowel disease in East China

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