When Should Thiopurine Therapy During Sustained Remission in Inflammatory Bowel Disease be Stopped?_Juniper Publishers







Authored by Marisa Iborra

Abstract

Azathioprine is effective for maintenance of remission in inflammatory bowel disease, nonetheless, duration of efficacy and the dose response relationship has not been fully evaluated. Currently, there are no general recommendations yet that can help us selecting patients who would benefit from the discontinuation of TP without an increased relapse risk.

Keywords: Immuno suppression; Thiopurines; Azathioprine; Inflammatory bowel disease

Abbreviations: AZA: Azathioprine; IBD:Inflammatory Bowel Disease; CD: Crohn's Disease; UC: Ulcerative Colitis; anti-TNF: Anti-Tumour Necrosis Factor

Introduction

Azathioprine (AZA) have been used in clinical practice for more than 50 years and remain the mainstay of maintenance treatment for inflammatory bowel disease (IBD), either as alone and/or in combination with anti-tumour necrosis factor (anti-TNF) drugs [1]. Today, Thiopurine have demonstrated their capacity maintaining remission in the long-term in both Crohn's disease (CD) [2,3] and ulcerative colitis (UC) [4,5], and it seems that the effect does not disappear after for up to 5 years [6]. Moreover, during follow-up responders had a significantly reduced risk of intestinal surgery and perianal surgery [7].

Discussion

Despite increasing evidence of safety from several studies, a percentage of responders developed cancers, including nonmelanoma skin cancers [7,8]. A rare and usually fatal lymphoma, hepatosplenic T-cell lymphoma, has been related with younger IBD patients who received long-term therapy (at least 2 years) with Thiopurine [9]. Thiopurine use in IBD appears to be strongly related with an increased risk of Epstein-BARGH virus-positive lymphoma [10,11]. Recently, it has been linked immunosuppressive treatment with opportunistic infections during severe lymphopenia in IBD patients [12]. Regular monitoring of blood counts and liver test is required in order to early detection of bone mARGHow and liver toxicities [13,14].

Treatment strategies have changed accordingly. Presently, the early introduction of Immuno modulators and anti- TNF therapy targeting a window of opportunity before the development of potentially intestinal complications and they are capable of change the disease evolution. However, the clinicians unknown the best moment of therapy stopping once remission is achieved. Identifying IBD patients with increased risk of relapse after Thiopurine withdrawal during sustained clinical remission is essential for appropriate management.

From a clinical point of view, our patients are young and have a long life expectancy. Physicians should consider maintaining thiopurinesonly in cases in which a clear benefit is expected. On the other hand, whether or not AZA can be stopped is an important question and factors involved in the decision to removal the drug in patients with IBD are necessary. Previous retrospective study suggested that the risk of relapse appeared to be similar if we withdrawal or maintain AZA after 4 years of remission in CD patients [15]. In Table 1 you can see the most relevant studies assessing relapse rate in IBD patients under immuno suppressive therapy in case of discontinuation as well as the predictive factors.

AZA (Azathioprine), 6-MP (6 mercaptopurine), CPR ( C reactive protein), UC (ulcerative colitis), CD (Crohn's disease)

Conclusion

In conclusion, Thiopurine withdrawal in the context of sustained remission is associated with a high risk of relapse. Currently discontinuation of AZA may be considered after 4 years in IBD patients in sustained remission and steroid free [24,25]. Further investigations are necessary in order to identify risk factors of relapse after stopping immunosuppressive therapy The safety and actual risk/benefit ratio of therapy withdrawal needs to be studied in prospective controlled trials, given the need to optimize the use and duration of potentially risky and costly therapies.

Conflict of Interest

No financial support was received for the preparation of this study. The authors declare that no conflict of interest exists.




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