Noviello D, Fries W, Orlando A, Conforti F S, Bezzio C, Castiglione F, Fantini M C, Savarino E V, Festa S, Ribaldone D G, Mocci G, Grossi L, Viganò C, Imperatore N, Ceccarelli L, Gabrielli A M Carvalhas, Scardino G, Saibeni S, Balestrieri P, Principi M, Campigotto M, Gravina A G, Spagnuolo R, Scaldaferri F, Neri B, Sario A Di, Baldoni M, Mitri R Di, Tettoni E, Calderone S, Armuzzi A, Macaluso F S, Vecchi M, Ventimiglia M, Caprioli F
University of Milan, Department of Pathophysiology and Transplantation, Milano, Italy.
University of Messina, Dept. of Clinical and Experimental Medicine, Messina, Italy.
Dig Liver Dis. 2025 May 6. doi: 10.1016/j.dld.2025.04.025.
Drug positioning in ulcerative colitis (UC) patients refractory to anti-tumor necrosis factor (TNF) is still debated. In a nationwide multicentre observational cohort, we aimed to compare the real-life effectiveness and safety of tofacitinib and vedolizumab as second-line for UC after anti-TNFs.
Disease activity was evaluated at weeks 8, 26, and 52 ± 4. The primary outcome was to compare clinical remission (partial Mayo score (PMS) ≤2 with no subscore >1) at week 26. Secondary outcomes included comparative effectiveness for corticosteroid-free clinical remission (CFCR); biochemical, endoscopic, and histologic remission; combined corticosteroid-free clinical-objective remission; and treatment persistence. Inverse probability of treatment weighting was used for all comparisons.
Overall, 134 tofacitinib- and 277 vedolizumab-treated UC patients were included. At week 26, no difference was observed between tofacitinib and vedolizumab for clinical remission (adjusted odds ratio [aOR]: 0.9; 95 % confidence interval [CI]: 0.6 - 1.6). At week 8, tofacitinib was more effective in achieving CFCR (aOR: 1.7; 95 % CI: 1.0 - 2.7). Clinical, biochemical, endoscopic, and histologic outcomes showed no difference between tofacitinib and vedolizumab at weeks 26 and 52. In patients with baseline PMS ≥ 2, steroid use, or anti-TNF non-response no difference was found for clinical remission at week 26. Tofacitinib-treated patients were more likely to discontinue treatment (adjusted Hazard Ratio: 1.8; 95 % CI: 1.2 - 2.8). Safety was consistent with treatment profiles in UC.
Tofacitinib and vedolizumab were equally effective and safe as second-line therapy in anti-TNFs experienced UC patients. Tofacitinib showed greater efficacy in inducing CFCR at week 8, but carried higher discontinuation risk.
对于抗肿瘤坏死因子（TNF）治疗无效的溃疡性结肠炎（UC）患者，药物选择仍存在争议。在一项全国性多中心观察性队列研究中，我们旨在比较托法替布和维多珠单抗作为抗TNF治疗后UC二线治疗药物的实际疗效和安全性。
在第8、26和52±4周评估疾病活动度。主要结局是比较第26周时的临床缓解情况（部分梅奥评分（PMS）≤2且各分项评分均不>1）。次要结局包括无糖皮质激素临床缓解（CFCR）的比较疗效；生化、内镜和组织学缓解；无糖皮质激素临床客观缓解；以及治疗持续性。所有比较均采用治疗权重逆概率法。
总体而言，纳入了134例接受托法替布治疗和277例接受维多珠单抗治疗的UC患者。在第26周时，托法替布和维多珠单抗在临床缓解方面无差异（调整后的优势比[aOR]：0.9；95%置信区间[CI]：0.6 - 1.6）。在第8周时，托法替布在实现CFCR方面更有效（aOR：1.7；95%CI：1.0 - 2.7）。在第26周和52周时，托法替布和维多珠单抗在临床、生化、内镜和组织学结局方面无差异。在基线PMS≥2、使用糖皮质激素或抗TNF治疗无效的患者中，第26周时临床缓解情况无差异。接受托法替布治疗的患者更有可能停药（调整后的风险比：1.8；95%CI：1.2 - 2.8）。安全性与UC的治疗特征一致。
在接受过抗TNF治疗的UC患者中，托法替布和维多珠单抗作为二线治疗同样有效且安全。托法替布在第8周诱导CFCR方面显示出更高的疗效，但停药风险更高。
