Sustained Clinical Efficacy and Mucosal Healing of Thiopurine Maintenance Treatment in Ulcerative Colitis: A Real-Life Study

Abstract

Background and Aims Thiopurines are commonly used for treating ulcerative colitis (UC), despite the fact that controlled evidence supporting their efficacy is limited. The aim of this study was to evaluate the long-term outcome of thiopurines as maintenance therapy in a large cohort of UC patients. Methods All UC patients receiving thiopurine monotherapy at three tertiary IBD centers from 1995 to 2015 were identified. The primary endpoint was steroid-free clinical remission. Secondary endpoints were mucosal healing (MH), defined as Mayo endoscopic subscore 0, long-term safety, and predictors of sustained clinical remission. Results We identified 192 patients, contributing a total of 747 person-years of follow-up (median follow-up 36 months, range 1–210 months). Steroid dependency was the most common indication for thiopurine treatment (58%). Steroid-free remission occurred in 45.3% of patients; 36.3% stopped thiopurines because of treatment failure and 18.2% for adverse events or intolerance. The cumulative probability of maintaining steroid-free remission while on thiopurine treatment was 87%, 76%, 67.6%, and 53.4% at 12, 24, 36, and 60 months, respectively. MH occurred in 57.9% of patients after a median of 18 months (range 5–96). No independent predictors of sustained clinical remission could be identified. Conclusions Thiopurines represent an effective and safe long-term maintenance therapy for UC patients.

Thiopurines: Recent Topics and Their Role in the Treatment of Inflammatory Bowel Diseases

“…The frequency of AEs in patients with IBD varies from 9% to 35%, depending on the study (Fraser et al, 2002;Timmer et al, 2016;Kakuta et al, 2018;Gjuladin-Hellon et al, 2019). Table 1 shows the frequency of AEs after thiopurine treatment in IBD (Kakuta et al, 2018;Pugliese et al, 2018;Özgenç et al 2018;Calafat et al, 2019). Moreover, the appearance of AEs is substantially related to racial differences (Kakuta et al, 2018).…”

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

“…11 12 To gain further insight, single-centre retrospective studies in population-based cohorts have investigated the real-world outcomes of AZA and 6MP treatment in IBD and suggested 40%-60% effectiveness. [13][14][15][16][17][18] Again, however, the numbers involved have been relatively modest and/or the follow-up relatively short, and few studies have compared effectiveness in UC versus CD. 13 15-18 The effect of thiopurines in reducing surgery has also been studied.…”

Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy

“…Thiopurines comprising azathioprine (AZA) and its active metabolite mercaptopurine as well as thioguanine, are also widely used in the therapy of chronic active IBD[ 38 - 40 ]. The most widely used preparations are AZA and mercaptopurine, which have also been recorded to help in mucosal healing in about 60% of the patients[ 38 , 39 ]. These drugs are activated after being metabolized into 6-thioguanine-nucleotides which disturbs proper DNA synthesis.…”

“…The IBD-healing process is accompanied by mucosal healing which is defined by the restoration of the intestinal lining, and is generally characterized by regression or disappearance of endoscopic lesions[ 61 ]. Although, the definition of the term mucosal healing remains debatable, in general, it refers to the resolution of ulcers in IBD in a follow-up endoscopic evaluation[ 38 ]. Complete mucosal healing has been defined by the absence of ulcerations during follow-up endoscopy in patients who had ulcerations present in baseline ileocolonoscopy exam and partial mucosal healing evident by clear endoscopic improvement but still with ulceration present[ 61 - 64 ].…”

“…Complete mucosal healing has been defined by the absence of ulcerations during follow-up endoscopy in patients who had ulcerations present in baseline ileocolonoscopy exam and partial mucosal healing evident by clear endoscopic improvement but still with ulceration present[ 61 - 64 ]. Mucosal healing is being considered as a mile-stone in IBD healing[ 64 ], and the logic behind considering this as the ultimate goal of all types of therapeutic interventions is based on the available set of evidence that it is often associated with better long-term outcomes for patient, defined by a number of factors like: Reduced risk of relapse, decreased hospitalization rates, increased steroid-free remission in the follow-up examination, and comparatively a longer resection free intervals[ 38 ]. Also, it was shown that patients with CD with mucosal healing have a decreased risk of penetrating complications and, thereby, decreased probability of surgery and progression to colon cancer[ 64 ].…”