Azathioprine or 6-Mercaptopurine for maintenance of remission in Crohn's disease

Department of Community Health Sciences, University of Calgary, Health Sciences Centre, 3330 Hospital Dr NW, Calgary, Alberta, Canada, T2N 4N1.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 01/2009; 1(1):CD000067. DOI: 10.1002/14651858.CD000067.pub2
Source: PubMed


Azathioprine (1.0 to 2.5 mg/kg/day) used among patients with non-active Crohn's disease is effective for reducing the risk of disease recurrence over a 6 month to 2 year period. Higher doses of azathioprine (2.5 mg/kg/day) are more effective than lower doses (1.0 or 2.0 mg/kg/day) for preventing disease recurrence. There is also evidence that azathioprine may reduce the need for steroid treatment which could help reduce steroid related side effects. 6-Mercaptopurine may be effective for reducing the risk of disease recurrence over a 2 year period. Azathioprine appears to be more effective than 6-mercaptopurine but this may be due to the relatively low dose of 6-mercaptopurine (50 mg/day) used in the one study assessing this drug. Future studies should assess the effect of higher doses of 6-mercaptopurine. The long-term effectiveness of azathioprine and 6-mercaptopurine is unclear due to the short duration of the studies (6 months to 2 years). Azathioprine and 6-mercaptopurine appear to be slow acting drugs. They are associated with some uncommon but serious side effects. These include suppression of the body's ability to produce white blood cells (which fight infection) and platelets (which allow blood clotting to occur), inflammation of the pancreas and an increased risk of lymphoma. Patients who may benefit from this therapy include those whose Crohn's disease is chronically active or flares frequently. Azathioprine or 6-mercaptopurine may also benefit patients who are dependent on steroids but have experienced steroid side effects, or for whom steroids no longer work. The choice to use azathioprine or 6-mercaptopurine should be made after careful consideration of the risks and benefits of using these drugs.

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    • "Immunomodulation with e.g., azathioprine (AZA) or 6 mercaptopurine (6MP) and biological therapies, e.g., infliximab (IFX), have shown well documented beneficial effects on the disease [4] [5]. However, both therapy strategies have been of concern regarding the influence of healing of anastomoses and a possible increased risk of postoperative anastomotic complications , with diverging results from previous studies [6– 16]. "
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    ABSTRACT: The aim of this study was to examine the effect of colitis and anti-inflammatory therapies on the healing of colonic anastomoses in mice. Female C57BL/6 mice were randomized into eight groups; four groups receiving plain tap-water and four groups receiving dextran sulfate sodium. Intra-peritoneal treatment was given therapeutically for 14 days with placebo, prednisolone, azathioprine, or infliximab (IFX). Colonic anastomoses were performed and bursting pressure (BP) measurements were recorded and the inflammation evaluated with histology and zymography. The mice with colitis had a more active inflammation based on histology and bowel weight compared with the tap water group, 8.3 (7.6-9.5) mg/mm and 5.5 (4.8-6.2) mg/mm respectively (p < 0.0001). Similarly mice with colitis receiving placebo had a more active inflammation, 12.8 (10.6-15.0) mg/mm, which differed significantly from all the other therapy arms among the colitic mice; prednisolone 8.1 (7.5-9.1) mg/mm (p = 0.014), azathioprine 8.2 (7.0-8.5) mg/mm (p = 0.0046), IFX 6.7 (6.4-7.9) mg/mm (p = 0.0055). BP for the placebo group was 90.0 (71.5-102.8) mmHg and did not differ from azathioprine or IFX groups, 84.4 (70.5-112.5) and 92.3 (75.8-122.3) mmHg respectively. In contrast BP for the prednisolone group was significantly decreased compared to placebo, 55.5 (42.8-73.0) mmHg (p = 0.0004). All therapies had a beneficial effect on the colitis. An impaired BP of colonic anastomoses was noted after preoperative steroids but not after azathioprine or IFX in this model.
    Full-text · Article · Apr 2015 · Scandinavian Journal of Gastroenterology
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    • "In order to minimize occurrence of the associated complications or the need for surgery, patients have to take long-term medicines to control activity of disease and prevent relapse. For the maintenance of remission, immunomodulators (such as thiopurines and methotrexate) and anti-tumor necrosis factor-alpha monoclonal antibody have proven to be highly efficient [1,2]. They not only decrease CD clinical activity but also heal the mucosa of ulcers and erosions [3,4], reduce the need for corticosteroids, and improve the patient’s quality of life. "
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    ABSTRACT: Azathiopurine (AZA) is efficacious for maintenance remission of Crohn's disease (CD) at the standard dose of 2.0-2.5 mg/kg for Caucasian. It has been reported that the lower dose (1.0-2.0 mg/kg) in some Asian countries was as effective as the standard dose. In the present study we analyzed the efficacy of <1.0 mg/kg AZA in maintaining remission for Chinese patients. The clinical data of all CD patients were reviewed from 1993 to December 2012. The patients who initiated AZA treatment and were followed for >= 2 years with complete medical data were included. We divided the patients into two groups according to their initial dose: <1.0 mg/kg group and 1.0-2.0 mg/kg group. Among 77 patients, 39 (50.6%) started treatment with <1.0 mg/kg AZA and 38 (49.4%) with 1.0-2.0 mg/kg. The mean dose of <1.0 mg/kg group remained under 1.0 mg/kg at 6, 12 and 24 months, even if the doses were adjusted according to efficacy and tolerance. The remission rate in patients of <1.0 mg/kg group was significantly higher than that in those of 1.0-2.0 mg/kg group (P = 0.025). A dose of <1.0 mg/kg AZA was more commonly associated with male gender, older age, heavier body weight and L1 location. Adverse events were observed in 21 of 77 patients (27.3%) and no significant difference in occurrence of adverse events or leucopenia between two groups. <1.0 mg/kg AZA was effective as 1.0-2.0 mg/kg in maintaining remission among Chinese patients with CD.
    Full-text · Article · Sep 2013 · Journal of Translational Medicine
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    • "According to these recommendations, CD remission should be induced with systemic CSS, using first Ôtopically acting' steroids (budesonide) only in mild-to-moderate localized ileo-cecal CD (Travis et al, 2006). Thiopurines (or, if intolerant, methotrexate; all these drugs are traditionally referred to as immuno-suppressive) should be added for those who have relapsed, because of their efficacy in steroid-sparing and maintaining remission, but should be started simultaneously in extensive, moderate– to-severe small bowel disease and are drugs of first choice in CSS-refractory disease (Travis et al, 2006; Prefontaine et al, 2009, 2010). Infliximab should be reserved for steroid and immuno-suppressive refractory disease, or intolerance, or steroid dependence (in this latter case, in addition or as an alternative to an immuno-suppressive, upon its failure), albeit surgical options should also be considered and discussed in these more complex cases. "
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    ABSTRACT: Oral Diseases (2011) 18, 1–15 This review focuses on the prominent etiological and pathogenetic aspects of inflammatory bowel disease (IBD), with particular attention being paid to the mucosal immune response to commensal micro-organisms in health and disease. Pathogenetic implications for target therapy will also be discussed. The clinical presentation, diagnostic aspects, and currently recommended therapeutic options for the two main types of IBD are also taken into consideration, including manifestations of these conditions in the oral cavity.
    Full-text · Article · Apr 2011 · Oral Diseases
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