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P468 Long-term efficacy and safety of thiopurine in biologic-naïve Japanese patients with ulcerative colitis: a multicentre retrospective study

T. Takagi*1, M. Matsuura2, S. Yamada2, S. Bamba3, Y. Hotta1, K. Uchiyama1, Y. Naito1, H. Nakase2, A. Andoh3, T. Kawamura4, S. Katsushima5, T. Kusaka6, H. Obata7, T. Kogawa8

1Kyoto Prefectural University of Medicine, Molecular Gastroenterology and Hepatology, Kyoto, Japan, 2Kyoto University Hospital, Department of Gastroenterology and Hepatology, Kyoto, Japan, 3Shiga University of Medical Science, Department of Medicine, Otsu, Japan, 4Kyoto Second Red Cross Hospital, Kyoto, Japan, 5National Hospital Organisation Kyoto Medical Centre, Kyoto, Japan, 6Kyoto Katsura Hospital, Kyoto, Japan, 7Obata Medical Clinic, Kyoto, Japan, 8Kogawa Internal Medicine Clinic, Internal Medicine Clinic, Kyoto, Japan

Background

Thiopurines are effective drugs in the patients with refractory ulcerative colitis (UC). However, long-term data regarding efficacy and safety of thiopurines in UC is lacking. In this study, we evaluated the effectiveness of thiopurines in a large cohort of bio-naïve UC patients in Japan.

Methods

Data were retrospectively obtained from the total 2 241 Japanese patients with UC of the 9 hospitals in Kyoto-Shiga regions during December 1998–August 2015. In total, 244 bio-naïve UC patients who achieved clinical remission after induction therapies except for biologics and maintained remission with thiopurines were enrolled in this study. The primary endpoint was the proportion of patients who maintained remission successfully. Secondary endpoints included colectomy-free survival, achievement of mucosal healing, and treatment safety. Clinical remission was defined as modified Truelove–Witts severity index (MTWSI) score of 4 or less. Relapse of UC was defined as an MTWSI score increase of at least 3 points from the baseline and need for induction treatment with other than thiopurine and mesalamine. For maintenance treatment with thiopurines, the dose of thiopurines was adapted to achieve white blood cell count (3 000–5 000/uL) or 6-thioguanine nucleotide concentration (235–450 pmol/8 × 108 erythrocytes). Mucosal healing was defined as Mayo endoscopic sub-score of 0 or 1.

Results

Mean age of 244 patients was 37.3 years (13–83 years). The median disease duration from diagnosis of UC to initiation of thiopurine treatment was 59.1 months (1–292 months). Further, 145 (59.4%) patients had refractory UC (steroid dependent in 118 patients [48.4%] and steroid resistant in 27 patients [11.0%]). The proportion of UC patients maintaining remission at 1, 3, 5, and 8 years were 84.1%, 69.6%, 59.2%, and 45.6%, respectively. Amongst 73 patients (29.9%) who had a UC relapse during the study period, 16 patients (6.6%) ultimately required biologic therapy, and 6 patients (2.5%) underwent colectomy. Kaplan–Meier analysis revealed that cumulative colectomy-free survival in 244 UC patients receiving maintenance treatment with thiopurines was 89.8% at 132 months. Out of 136 patients who underwent colonoscopy during thiopurine maintenance treatment, 107 patients (78.7%) achieved mucosal healing. Out of 244 UC patients, 30 patients (12.3%) discontinued thiopurines because of adverse events, including liver dysfunction (4.9%), nausea (2.9%), and leukopenia (2.0%).

Conclusion

These large-cohort data indicate that maintenance treatment with thiopurines is effective and safe in Japanese patients with bio-naïve UC. Optimal use of thiopurines contributes to long-term clinical benefits in bio-naïve UC patients.