Johnsen Kay-Martin, Goll Rasmus, Hansen Vegard, Olsen Trine, Rismo Renathe, Heitmann Richard, Gundersen Mona D, Kvamme Jan M, Paulssen Eyvind J, Kileng Hege, Johnsen Knut, Florholmen Jon
aResearch Group of Gastroenterology and Nutrition, Department of Clinical Medicine, University of Tromsø bDepartment of Nephrology and Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø cDepartment of Medicine, Telemark Hospital, Skien dDepartment of Medicine, Division of Hammerfest, Finnmark Hospital, Hammerfest, Norway.
Eur J Gastroenterol Hepatol. 2017 Jan;29(1):98-104. doi: 10.1097/MEG.0000000000000753.
Anti-tumour necrosis factor (TNF) agents play a pivotal role in the treatment of moderate to severe ulcerative colitis (UC), and yet, no international consensus on when to discontinue therapy exists.
The aim of this study is to study the long-term performance of a treatment algorithm of repeated intensified induction therapy with infliximab (IFX) to remission, followed by discontinuation in patients with UC.
Patients with moderate to severe UC were enroled in an open prospective study design. The following algorithm was implemented: (a) intensified induction treatment to remission (Ulcerative Colitis Disease Activity Index score 0-2); (b) discontinuation of IFX; and (c) reinduction treatment if relapse. Mucosal gene expression for TNF was measured with qPCR.
A total of 116 patients were included. The median observation time was 47 and 51 months in intention to treat and per protocol. Remission rates of the first three inductions were 95, 93 and 91% per protocol and 83, 56 and 59% by intention to treat. The median time in remission was 40 months per protocol and 34 months by intention to treat. Long-term remission without further anti-TNF treatment during the observation period was obtained for 41%, with a median observation time of 48 months (range: 18-129 months). The median time to relapse was 33 and 11 months with/without normalization of mucosal TNF, respectively. The 5-year success rate for maintaining the effect of IFX in the algorithm was 66%.
The treatment algorithm is highly effective for achieving long-term clinical remission in UC. Normalization of mucosal TNF gene expression predicts long-term remission upon discontinuation of IFX.
抗肿瘤坏死因子（TNF）药物在中重度溃疡性结肠炎（UC）的治疗中起着关键作用，然而，对于何时停止治疗尚无国际共识。
本研究旨在探讨英夫利昔单抗（IFX）重复强化诱导治疗至缓解，随后在UC患者中停药的治疗方案的长期疗效。
中重度UC患者纳入开放性前瞻性研究设计。实施以下方案：（a）强化诱导治疗至缓解（溃疡性结肠炎疾病活动指数评分0 - 2）；（b）停用IFX；（c）复发时重新诱导治疗。用qPCR检测TNF的黏膜基因表达。
共纳入116例患者。意向性分析和符合方案分析的中位观察时间分别为47个月和51个月。按符合方案分析，前三次诱导缓解率分别为95%、93%和91%，意向性分析分别为83%、56%和59%。按符合方案分析，缓解的中位时间为40个月，意向性分析为34个月。41%的患者在观察期内无需进一步抗TNF治疗即可长期缓解，中位观察时间为48个月（范围：18 - 129个月）。黏膜TNF正常化与否的复发中位时间分别为33个月和11个月。该方案中IFX维持疗效的5年成功率为66%。
该治疗方案在UC患者中实现长期临床缓解非常有效。黏膜TNF基因表达正常化可预测停用IFX后的长期缓解。
