Abstract Background Vedolizumab (VDZ) is commonly used as a first-line biologic therapy for moderate to severe ulcerative colitis (UC), but evidence on second-line treatment efficacy following vedolizumab failure is lacking. This study evaluated effectiveness of infliximab and JAK Inhibitors (tofacitinib and upadacitinib) as second-line treatment options after VDZ failure in moderate-severe UC. Methods This multi-center retrospective observational cohort study included all patients with UC who received VDZ as first-line therapy between January 2015 and September 2024, followed by second-line treatment with infliximab, tofacitinib, or upadacitinib were included. The primary outcome was clinical response at week 26. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥ 3 points, and SCCAI ≤2 or a PMS ≤1, respectively. Secondary outcomes included week 52 response, remission, and drug persistence. Results We included 89 patients who failed on VDZ as a first-line treatment for UC; 58 patients received second-line infliximab (65.2%) and 31 (34.8%) received second-line JAK inhibitors (26 tofacitinib, 5 upadacitinib). The median duration of VDZ treatment as a first-line therapy was 11 months (IQR 7-21). At week 26, no significant difference was observed between infliximab and JAK inhibitors for clinical response (67% vs. 78%, p = 0.4) and clinical remission (39% vs. 61%, p = 0.1). At week 52, clinical response (73% vs. 77%, p = 1) and clinical remission rates (60% vs. 77%, p = 0.49) were similar between infliximab and JAK inhibitors, respectively. A sensitivity analysis restricted to patients treated with infliximab or tofacitinib demonstrated similar results at week 26 (clinical response 67% vs 71%, p = 0.77 and clinical remission 39% vs 50%, p = 0.45, respectively). Median drug survival at week 52 was 50.9% (95% CI 39.4%-65.7%) for infliximab and 41.4% (95% CI 26.8%-63.8%) for JAK inhibitors (p = 0.2). Three patients (3.3%) had an adverse event (2 infliximab, 1 JAK inhibitors) leading to therapy discontinuation. Conclusion Following first-line VDZ failure in UC patients, infliximab and JAK inhibitors demonstrated comparable efficacy, safety and persistence of treatment. Conflict of interest: Dr. Shohat, Omer: No conflict of interest Weisshof, Roni: No conflict of interest Glusman-Bendersky, Ahinoam: No conflict of interest Ollech, Jacob: No conflict of interest Yanai, Henit: Grant: Pfizer, ISF Personal Fees: AbbVie, Janssen, Pfizer, Takeda, Bristol Myers Squibb, and Elly Lilli. Kopylov, Uri: Grant: Takeda, Janssen,Abbvie, Medtronic, Ely Lilly Other: Takeda, Janssen,Ely Lilly, Roche, Celtrion, Abbvie, Medtronic, CTS, Pfizer, BMS- speaker and advisory fees Levartovsky, Asaf: Honoraria and speaker fees from: Takeda, Sanofi, Rafa
Shohat et al. (Thu,) studied this question.