目的：缺乏关于JAK抑制剂和S1P受体调节剂在抗生素难治性慢性囊炎（CARP）中的有效性和安全性的数据。
方法：本ECCO-CONFER项目回顾性收集JAK抑制剂或S1P受体调节剂治疗CARP的至少3个月随访。结果包括3个月和12个月时无皮质类固醇和抗生素的临床反应和缓解，MPDAI的趋势，内窥镜PDAI,CRP和钙卫蛋白。
结果：收集了15例患者的17种治疗方法。以前的囊炎治疗包括英夫利昔单抗（5/15），阿达木单抗（4/15），维多珠单抗（9/15），和ustekinumab（5/15）。JAK抑制剂的汇总数据(8托法替尼，1菲尔戈替尼和6upadacitinib），3个月后（T3），无类固醇和抗生素的临床反应达到53.3%(8/15)，无类固醇和抗生素的临床缓解率达到40%(6/15).在随访至少12个月的患者中，无类固醇和抗生素的临床反应在50％（3/6）和缓解在一个患者（16.7％），内镜反应50%(3/6),内镜下缓解50%(3/6)。在T3时的两种ozanimod治疗中，一名患者获得了无类固醇和抗生素的临床反应，没有缓解；两者在T12之前都停止了奥扎尼莫德。没有副作用报告。
结论：小分子可能是多种生物制剂难治性CARP的合适选择，值得进一步调查。
OBJECTIVE: Data regarding the effectiveness and safety of Janus kinase [JAK] inhibitors and sphingosine-1-phosphate [S1P] receptor modulators in antibiotic refractory chronic pouchitis [CARP] are lacking.
METHODS: This ECCO-CONFER project retrospectively collected data for JAK inhibitor or S1P receptor modulator treatments for CARP with at least 3 months of follow-up. The outcomes included corticosteroid- and antibiotic-free clinical response and remission at 3 and 12 months, and trends in modified pouchitis disease activity index [mPDAI], endoscopic PDAI, C-reactive protein, and calprotectin.
RESULTS: Seventeen treatments in 15 patients were evaluated. Previous pouchitis treatments included infliximab [5/15], adalimumab [4/15], vedolizumab [9/15], and ustekinumab [5/15]. Pooling data on JAK inhibitors [eight tofacitinib, one
filgotinib, and six upadacitinib] after 3 months [T3], steroid- and antibiotic-free clinical response was achieved in 53.3% [8/15], and steroid- and antibiotic-free clinical remission was achieved in 40% [6/15]. Of the patients with at least 12 months of follow-up, steroid- and antibiotic-free clinical response was achieved in 50% [3/6] and remission in one patient [16.7%], endoscopic response in 50% [3/6], and endoscopic remission in 50% [3/6]. Of the two ozanimod treatments at T3, steroid- and antibiotic-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects were reported.
CONCLUSIONS: Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.
