熊谷 秀規

BACKGROUND: Although ulcerative proctitis (UP) in children is considered relatively mild, some patients have proximal disease extension and require immunosuppressive treatment. We investigated clinical characteristics and course of refractory UP in a multicenter pediatric cohort. METHODS: Analyzing data obtained between 2013 and 2022 at 10 institutions specializing in pediatric inflammatory bowel disease, we elucidated natural history and factors predicting a need for immunosuppressive UP treatment. We compared patients given immunosuppressants and/or biologic agents (immunosuppressive treatment group) with those given 5-aminosalicylic acid (5-ASA) alone (5-ASA group). RESULTS: Fifty-five patients were followed for 3.5 years. The median Pediatric Ulcerative Colitis Activity Index at diagnosis was 20. The commonest treatment, 5-ASA suppository monotherapy in 40% of patients, showed the worst compliance. Clinical remission was achieved at least once in 95% of all patients. Disease extension beyond the splenic flexure occurred in 51%. Immunosuppressive treatment was given to 37%; biologic agents were used for 18%. Rates of endoscopically demonstrated inflammation, including Ra/Rs at diagnosis and extension beyond the left-sided colon, were higher in the immunosuppressive treatment group (70% vs 38%, P < 0.05; 95% vs 27%, P < 0.0001). The log-rank test and multivariate Cox proportional hazards regression showed that time to first clinical remission exceeding 3 months predicted the need for biologics. CONCLUSION: The typical initial treatment of pediatric UP was 5-ASA suppositories, despite poor compliance. Biologics or other immunosuppressive treatments were needed in 37% of patients. Close follow-up with adjustment of treatment should be considered in children with UP as its clinical course varies.

BACKGROUND AND AIM: Even with increasing numbers of biologic agents available for management of ulcerative colitis (UC), infliximab (IFX) retains an important place in treatment of pediatric patients with this disease. As few reports have addressed outcomes in pediatric UC patients who had to discontinue IFX, we examined clinical course and prognosis after IFX failure in pediatric UC. METHODS: A prospective cohort study of pertinent cases enrolled in the Japanese Pediatric Inflammatory Bowel Disease Registry between 2012 and 2020 was conducted to determine outcomes for pediatric UC patients who received IFX but required its discontinuation during follow-up (IFX failure). RESULTS: Of the 301 pediatric UC patients in the registry, 75 were treated with IFX; in 36 of these, IFX was discontinued during follow-up. Severity of UC at onset and absence of concomitant immunomodulator therapy were significant risk factors for IFX failure (P = 0.005 and P = 0.02, respectively). The cumulative colectomy rate after IFX failure was 41.3% at 1 year and 47.5% at 2 years. Colectomy was significantly more frequent when IFX was discontinued before June 1, 2018, than when IFX was discontinued later (P = 0.013). This difference likely involves availability of additional biologic agents for treatment of UC beginning in mid-2018 (P = 0.005). CONCLUSION: In pediatric UC patients, approximately 50% underwent colectomy during a 2-year interval following IFX failure. Prognosis after IFX failure appeared to improve with availability of new biologic agents and small-molecule drugs in mid-2018.