Evaluating the Optimal Treatment Sequence After Vedolizumab Failure in Ulcerative Colitis

Background: Various advanced therapies (AT) with different modes of action (MOA) are available for refractory ulcerative colitis (UC). After failure of a first AT, switching to another is common, but the optimal sequence remains unclear. We previously reported that TNFa inhibitors use does not affect ustekinumab (UST) efficacy, whereas vedolizumab (VDZ) use reduces it, and high expression of MMP-X in the mucosa is the potent biomarker for UST refractoriness. This study aimed to identify the effective MOA after VDZ failure.
Methods: We retrospectively analyzed patients who initiated VDZ at four institutions and subsequently switched to another AT.
Results: Among 108 VDZ-treated patients, 43 required a switch. The median age was 31 years, with a median disease duration of 4 years. The switched ATs included TNFa inhibitors (TNFa) (n=8), IL-12/23 (UST) or 23 inhibitors (IL) (n=24), and JAK inhibitors (JAK) (n=11). At weeks 24/52, clinical response rates were 13%/0% for TNFa, 50%/54% for IL, and 63%/60% for JAK. The used ATs at the time of final remission were TNFa in 3 cases (7%), IL in 20 cases (47%), and JAK in 15 cases (35%). Additionally, MMP-X, a myofibroblast activation marker, was relatively increased in VDZ non-responders.
Conclusion: Patients requiring a switch after VDZ failure exhibit low response rates to any AT, because of activation of myofibroblasts, but IL-12/23 or 23 inhibitors and JAK inhibitors appear more effective than TNFa inhibitors.