P597 Usefulness of histological monitoring in predicting relapse after de-escalation of thiopurines in Ulcerative Colitis
Yamana, Y.(1)*;Sagami, S.(1);Maeda, M.(1);Karashima, R.(1);Miyatani, Y.(1);Hojo, A.(1);Nakano, M.(1);Maeda, I.(2);Hibi, T.(1);Kobayashi, T.(1,3);
(1)Kitasato University Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan;(2)Kitasato University Kitasato Institute Hospital, Department of Diagnostic Pathology, Tokyo, Japan;(3)Kitasato University School of Medicine, Department of Gastroenterology, Kanagawa, Japan;
Background
Thiopurines are useful to maintain remission for ulcerative colitis (UC) and to inhibit immunogenicity in combination with biologics while their long-term use may increase risks of infections and malignancies. Therefore, the risk-benefit balance should be evaluated, and de-escalation needs to be discussed. However, optimal de-escalation strategy such as dosing and monitoring has not been well studied.
Methods
UC patients in clinical remission (partial Mayo score ≤ 2 and rectal bleeding subscore of 0) who de-escalated thiopurines (dose-reduction or discontinuation) were enrolled. The risk of relapse and changes in Mayo endoscopic subscore (MES) and histological findings after thiopurine de-escalation were retrospectively investigated. The correlation with relapse (treatment escalation (including topical therapy) with the exacerbation of symptoms or rectal bleeding score ≥ 1) was analyzed by logistic regression analysis.
Results
A total of 69 de-escalation steps (51 dose-reductions and 18 discontinuations) were conducted in 39 patients. The mean duration and dose of thiopurine use were 3.5 years and 66.6mg (converted to azathioprine). Thiopurines were used in combination with biologics in 16 (41.0%). Relapse occurred in 17/69 (24.6%) de-escalation steps (10/17 discontinuations). In 36 de-escalations remaining in remission with available data before and after de-escalations, worsening of MES occurred in 13%, whereas exacerbations of any histopathological finding occurred in 44% (crypt architectural irregularities 25%, chronic inflammatory cell infiltrate 19％, acute inflammatory cell infiltrate 16％, basal plasmacytosis 13%, mucin depletion 13%, crypt abscess 8%). Chronic inflammatory cellular infiltrate (p=0.002), basal plasmacytosis (p=0.008), and acute inflammatory cell infiltrate (p=0.039) at de-escalation were significantly associated with relapse after de-escalation. Nancy Index was also associated with relapse (p=0.011), while MES was not.
Conclusion
Histological worsening may precede clinical relapse thus may be useful to predict relapse after thiopurine withdrawal.