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.