Impact of Prior Biologic Exposure on the Long-Term Durability of Clinical and Mucosal Efficacy in Patients With Ulcerative Colitis Treated With Ozanimod

Introduction: Ozanimod (OZA) is approved for the treatment of moderately to severely active ulcerative colitis (UC). Induction and maintenance of mucosal healing (MH) is associated with improved long-term UC outcomes. Previous analyses have demonstrated that patients (pts) who achieved stringent MH at Week (W) 10 on OZA treatment demonstrated better outcomes at W52 than those with standard MH. This analysis of the phase 3 True North (TN) open-label extension (OLE) explored the impact of prior biologic exposure on the maintenance of long-term OZA efficacy in pts who achieved standard vs stringent MH at TN W52 before OLE entry. Methods: The analysis evaluated TN pts who achieved MH using a standard definition (ie, mucosal endoscopy subscore [MES] ≤1 + histologic remission [HRem; Geboes score < 2.0]) at TN W52 while on continuous OZA treatment and entered the OLE. Of these pts, those who achieved stringent MH (MES=0 + HRem) at TN W52 were also assessed. Standard and stringent MH groups were categorized into subgroups based on prior biologic status (biologic-naive [bio-naive] or biologic-exposed [bio-exp]). Clinical (clinical response, clinical remission, corticosteroid-free remission, and endoscopic improvement) and mucosal (HRem, standard MH, and stringent MH) efficacy endpoints were evaluated at OLE W46 and W94. Results: Of 230 pts who completed TN W52 while on continuous OZA, 26% (59/230) achieved standard MH at OLE entry (bio-naive: n=43; bio-exp: n=16). Of these 59 pts, 59% (n=35, of whom 31 were bio-naive) also achieved stringent MH. TN baseline demographics were generally similar across treatment groups except bio-exp pts had longer disease duration and more extensive UC than bio-naive pts. Overall, the percentages of pts with standard or stringent MH at TN W52 who achieved the evaluated clinical and mucosal endpoints were generally similar regardless of prior biologic use (Figure 1). Clinical endpoints were generally sustained through OLE W94 in both standard and stringent MH groups (Figure 1). The maintenance of mucosal endpoints over 94 wk in the OLE was similar regardless of prior biologic exposure (Figure 1). Conclusion: In TN, more bio-naive than bio-exp pts achieved standard or stringent MH after 52 wk of OZA treatment. Durability of clinical and mucosal efficacy of OZA was similar over 2 years during the OLE in pts with MH regardless of prior biologic exposure, indicating that attainment of mucosal efficacy is a predictor of clinical durability even in pts with prior biologic failure.Figure 1.: Clinical and mucosal efficacy of OZA at OLE W46 and W94 by prior biologic use in TN W52 OZA clinical responders with (A) standard MH or (B) stringent MH at OLE entry.