Efficacy and Safety of Vedolizumab and Tofacitinib ( VETO ) Combination Therapy in Refractory Ulcerative Colitis Unresponsive to Anti‐ TNF and a Second‐Line Advanced Therapy: A Prospective Cohort Nested Within a Randomised Trial

ABSTRACT Background Management of refractory ulcerative colitis (UC) unresponsive to advanced therapies is challenging. Combination therapy is a potential strategy. Aim To evaluate the safety and efficacy of vedolizumab and tofacitinib combination (VETO) therapy in patients with UC refractory to anti‐TNF and unresponsive to either agent as monotherapy. Methods We prospectively recruited patients with moderate‐to‐severe disease activity (Mayo score: 6–12). Patients were randomised to receive vedolizumab or tofacitinib. Non‐responders were offered VETO therapy and followed for 24 weeks. The primary outcome was a combined clinical response and corticosteroid‐free remission at week 24. Secondary outcomes included clinical response and remission at week 8, endoscopic remission at week 24 and incidence and severity of treatment‐related adverse events. Results Of 91 patients, 38 were randomised to vedolizumab and 40 to tofacitinib. Fourteen and 15, respectively, were non‐responders to vedolizumab and tofacitinib; 24 received VETO with follow‐up of 34 ± 16.1 weeks. Median second‐line therapy duration before VETO was 21 weeks. Five non‐responders received alternative interventions or were lost to follow‐up. At week 8, 17 achieved clinical response and five achieved remission; three underwent colectomy. At week 24, response and corticosteroid‐free remission were seen in 17 and 14, respectively; 7 achieved endoscopic remission. Mayo scores improved significantly (mean difference 5.33 ± 0.53; p < 0.01). Two patients developed pseudomembranous colitis that resolved with vancomycin. No severe adverse events occurred. Conclusion VETO was effective and safe in patients with UC refractory to anti‐TNF and second‐line therapies, with over half achieving clinical remission by 24 weeks.