P427. Long-term outcomes of ulcerative colitis patients on thiopurine maintenance treatment
S. Yamada1, T. Yoshino1, N. Minami1, T. Toyonaga2, Y. Honzawa1, M. Matsuura1, H. Nakase1, 1Graduate school of Medicine, Kyoto University, Department of gastroenterology and hepatology, Kyoto, Japan, 2Kansai Medical University, The Third Department of Internal Medicine, Takatsuki, Japan
Thiopurines are used widely for treatment of refractory ulcerative colitis (UC), and have proven efficacy in treating active disease and maintaining remission. However, little is known about the long-term clinical outcome of the disease among bio-naïve UC patients who present a good response to thiopurine treatment. The aim of this study is to assess the long-term efficacy and safety of the maintenance treatment with thiopurines.
This was a retrospective observational cohort analysis at a single center. From December 1998 to August 2013, 59 of 87 bio-naïve UC patients who achieved remission after induction treatments except for biologics were enrolled. After induction treatment, all patients maintained remission with thiopurines. Remission maintenance was defined as no need for concomitant treatment other than 5-aminosalicylate without relapse for at least 3 months. Clinical remission was defined as the modified Truelove and Witts Severity Index (MTWSI) score less than 4. Relapse of UC was defined as an MTWSI score increase of at least 3 points from the baseline. For maintenance treatment with thiopurines, the dose of azathioprine or 6-mercaptopurine was adapted to achieve white blood cell count (3,000–5,000/uL) or 6-thioguanine nucleotide concentration (235–450 pmol/8×108 erythrocytes).
The primary endpoint was the proportion of patients who maintained remission successfully. Secondary endpoints included relapse-free survival, colectomy-free survival and treatment safety. Those survival curves were assessed using Kaplan–Meier method.
Mean age of 59 patients was 36.8 years (13–83 years). 14 were male and 19 were female. The extent of UC was included extensive colitis (66.1%), left-sided colitis (28.8%) and proctitis (5.1%).
The proportion of UC patients maintaining remission at 6, 12, 24, 48, 72, and 84 months were 91.2%, 80.0%, 65.2%, 51.9%, 51.9%, and 41.5%, respectively. Cumulative relapse-free survival and colectomy-free survival in UC patients receiving maintenance treatment with thiopurines were 41.5% and 93.8% at 84 months.
The thiopurines were discontinued because of side effects in 7 of 59 patients (11.9%). Side effects including upper respiratory disease (1.7%), infectious mononucleosis (1.7%), nausea (1.7%), liver dysfunction (3.4%), pancreatitis (1.7%), and leukopenia (1.7%) were found. All of patients recovered from side effects, and no mortality was observed.
Our study strongly demonstrated that long-term thiopurine benefits were observed, and physicians should consider use of thiopurines as a first line maintenance treatment for bio-naïve UC patients.