Real-World Long-Term Remission Maintenance for 10 Years With Thiopurines in Ulcerative Colitis

Background: To evaluate the therapeutic outcomes and long-term prognosis of patients receiving remission maintenance therapy using thiopurines for ulcerative colitis (UC). Methods: Of 193 biologic-naive patients with UC who began thiopurine therapy at our hospital between 2000 and 2019, 161 patients were included after the exclusion of 32 patients who were intolerant to thiopurines and discontinued the drugs within 3 months. Short- and long-term clinical outcomes were retrospectively analyzed. Subsequently, the patients were divided into 2 groups (exacerbation and nonexacerbation groups) and clinical outcomes were analyzed and compared. Multivariate analysis was performed to identify risk factors for UC exacerbation. Finally, adverse events observed in 193 patients were examined. Results: Clinical remission rates at 2 months, 6 months, and 1 year after the start of thiopurine therapy were 50.0%, 58.0%, and 63.9%, respectively. At 1, 2, 5, and 10 years, the cumulative event-free rates were 77.6%, 60.8%, 48.5%, and 42.2%, respectively; the cumulative UC exacerbation rates were 17.0%, 32.5%, 42.2%, and 43.7%, respectively; and the cumulative colectomy rates were 0.6%, 1.3%, 8.5%, and 10.7%, respectively. Prior use of steroids (dose >= 40 mg/d) was a significant risk factor for UC exacerbation during remission maintenance therapy with thiopurines (hazard ratio, 2.26; 95% confidence interval, 1.18-4.34; P = 0.014). Adverse reactions occurred in 42 patients (21.8%; 46 events). Concurrent diseases were observed in 18 patients (9.3%). Conclusions: Thiopurines were effective for long-term maintenance of remission in steroid-dependent/refractory UC. Their effect weakened in only a few patients continuously treated with them for 4 years or longer. Lay Summary Thiopurines were effective for long-term maintenance of remission in steroid-dependent/refractory ulcerative colitis. After approximately 4 years of thiopurine therapy, fewer patients experienced ulcerative colitis exacerbation, and thiopurines did not lose their efficacy, unlike biologics. Similar results were obtained for colectomy.