Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis.

German Cochrane Center, Stefan Meier Str. 26, Freiburg, Germany, 79104.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2007; DOI: 10.1002/14651858.CD000478.pub2
Source: PubMed

ABSTRACT Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial.
To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis.
The MEDLINE database was used to search literature from 1966 to 2006. A manual search was also performed using references from these articles as well as review articles, proceedings from major gastrointestinal meetings and data available from the Cochrane Collaboration database. Authors of maintenance trials were asked about unpublished studies.
Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (mesalamine) were included.
Data were extracted by two raters using standard forms. Disagreements were solved by informal consent, including a third rater. Jadad scores were applied to assess study quality. Analyses were performed separately by type of control (placebo, or active comparator). Pooled odds ratios were calculated based on the fixed effects model unless heterogeneity was shown.
Six studies were identified including 286 patients with ulcerative colitis. The study quality was mostly poor. Azathioprine was shown to be superior for the maintenance of remission as compared to placebo based on four trials (failure to maintain remission: OR 0.41; 95% CI 0.24 to 0.70). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity. Both studies using active comparators were open label. Adverse effects occurred in 11 of 127 patients receiving azathioprine, including acute pancreatitis (3 cases) and significant bone marrow suppression (5 cases).
Azathioprine may be an effective maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The role of thiopurines in altering the risk of colectomy in ulcerative colitis (UC) remains unclear.AimsTo examine predictors of colectomy in UC and determine the impact of thiopurines on the risk of colectomy.Methods We constructed a population-based cohort of incident cases of UC in the United Kingdom between 1989 and 2009. We determined trends in thiopurine usage and colectomy for three defined cohorts: era 1 (1989–1995), era 2 (1996–2002), era 3 (2003–2009). We used Cox regression to determine predictors of colectomy and quantified the impact of duration and timing of thiopurine use on the risk of colectomy.ResultsWe identified 8673 incident cases of UC. 5-year colectomy rates increased from 4.2%, 5.1% to 6.9% (P = 0.001) for era 1, era 2 and era 3, respectively, despite increasing thiopurine use. This was not significant after adjustment for predictors of colectomy (P = 0.06). There was a higher risk of colectomy in men (HR 1.44, 95% CI: 1.19–1.73), those diagnosed at an early age (HR 1.35, 95% CI: 1.04–1.75; 16–24 vs. 25–64) and early steroid users (HR 1.94, 95% CI: 1.59–2.37). 5-ASA users were less likely to require a colectomy (HR 0.35, 95% CI: 0.28–0.44). Amongst thiopurine users, those treated for greater than 12 months had a 71% reduction in risk of colectomy (HR 0.29, 95% CI: 0.21–0.40). Early thiopurines offered no additional benefit.Conclusions Thiopurine exposure for greater than 12 months reduces the likelihood of colectomy by 71%. Young men and those requiring steroids within 3 months of diagnosis are at greatest risk of colectomy, and most likely to benefit from sustained thiopurine use.
    Alimentary Pharmacology & Therapeutics 11/2014; · 4.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Most patients with inflammatory bowel diseases (IBD) are offered conventional medical therapy, because emerging therapies for IBD are regulated by health-care jurisdiction and often limited to academic centres. This review distils current evidence to provide a pragmatic approach to conventional IBD therapy, including aminosalicylates, corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, infliximab and adalimumab. It addresses drug efficacy, safety and salient practice points for optimal and appropriate practice.
    Scandinavian Journal of Gastroenterology 01/2015; 50(1):90-112. · 2.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The role of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the induction of remission in patients with ulcerative colitis (UC) remains unclear. Aims: To compare the efficacy and safety of low-dose thiopurine (AZA/6-MP) and cytapheresis (CAP) for the induction of remission in patients with steroid-dependent UC. Patients and Methods: We reviewed the clinical course of 65 patients with steroid-dependent UC with moderate activity, who were treated with either low-dose AZA/6-MP (T-group, n = 38) or with CAP (C-group, n = 27). The efficacy and safety for the first 10 weeks after the start of the therapies were compared between the two groups. The cumulative probability curves of treatment failure were estimated by the Kaplan-Meier method. Clinical remission was defined as an ulcerative colitis activity index value of less than 150 without any other treatments. Results: Neither clinical characteristics, concomitant therapies, nor laboratory data (except for serum albumin levels) were different between the two groups. The remission rate at 10 weeks was not different between the two groups (55.3% in the T-group and 70.4% in the C-group, p = 0.22 in the intention-to-treat analysis). The frequencies of adverse events did not differ be-tween the two groups (p = 0.12). The cumulative pro-bability of treatment failure at 10 weeks was 44.7% for the T-group and 29.6% for the C-group (p = 0.23). Conclusions: Low-dose thiopurine therapy is an alter-native candidate for the induction of remission in pa-tients with steroid-dependent, moderate UC.