S1027 Impact of Prior Biologic Exposure on the Durability of 3-Year Continuous Ozanimod Treatment

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Introduction: Ozanimod (OZA) is approved for the treatment (tx) of moderately to severely active (mod/sev) ulcerative colitis (UC). OZA demonstrated superior efficacy vs placebo in the 52-wk phase 3 True North (TN) study and demonstrated durable efficacy over ∼3 y of continuous tx in the open-label extension (OLE). Previous analyses reported greater clinical and mucosal efficacy during TN in biologic-naive (BN) vs biologic-experienced (BE) patients (pts). Methods: This analysis evaluated the effect of prior biologic exposure on the durability of OZA efficacy in pts with mod/sev UC. Pts who achieved clinical response (CRes) with/without remission after 52 wk of continuous OZA tx during TN and entered the OLE were evaluated (cutoff: 10Jan2022). Symptomatic CRes and clinical remission (CRem) were evaluated through OLE W94, and CRes, CRem, endoscopic improvement, and corticosteroid (CS)–free remission were evaluated at OLE W46 and W94 using observed case (OC) and nonresponder imputation (NRI) analyses. Data were analyzed by prior biologic exposure at baseline. Pts exposed to only a Janus kinase inhibitor were not included in this analysis. Results: 128 pts with prior biologic information entered the OLE after achieving CRes on continued OZA at TN Week (W) 52 (BN, n=82; BE, n=46). Baseline characteristics in TN were generally balanced between groups, except for longer disease duration, higher CS use at screening, and higher prior immunomodulator use in BE pts. Complete and partial Mayo scores were higher in BE pts at OLE entry. In OC analyses, symptomatic response at OLE W5 was achieved by 100% of BN and BE pts. At OLE W5, 90.8% of BN pts and 72.1% of BE pts achieved symptomatic remission. Rates of symptomatic CRes and CRem were maintained through OLE W94. In pts with CRes with or without remission at TN W52, the proportions of BN and BE pts achieving CRes, CRem, endoscopic improvement, and CS-free remission at OLE W46 and W94 are shown in Table 1. Greater efficacy was observed in BN vs BE pts across all endpoints. Pts in CRem at TN W52 showed similar efficacy rates in BN and BE pts, whereas BN pts demonstrated greater efficacy than BE pts in those without CRem at TN W52. Similar patterns were seen using NRI analysis. Conclusion: Clinical and symptomatic outcomes were maintained in BN and BE pts with mod/sev active UC receiving ∼3 y of continuous OZA tx. Greater efficacy was generally observed in BN pts, but BN and BE pts who achieved CRes with remission at TN W52 had similar efficacy during the OLE. Table 1. - Efficacy at OLE. W46 and OLE W94 by biologic exposure at baseline and clinical response at W52/OLE entry (OC analysis) Biologic-naive (n=82)Clinical response at TN W52a Biologic-experienced (n=46)Clinical response at TN W52a Biologic-naive (n=58)Clinical remission at TN W52b Biologic-experienced (n=22)Clinical remission at TN W52b Biologic-naive (n=24)Clinical response (without remission) at TN W52c Biologic-experienced (n=24)Clinical response (without remission) at TN W52c Clinical response,a % (n/N) OLE W46 95.2 (60/63) 96.8 (30/31) 95.7 (44/46) 100.0 (17/17) 94.1 (16/17) 92.9 (13/14) OLE W94 90.9 (50/55) 92.0 (23/25) 95.0 (38/40) 92.3 (12/13) 80.0 (12/15) 91.7 (11/12) Clinical remission,b % (n/N) OLE W46 77.8 (49/63) 61.3 (19/31) 82.6 (38/46) 82.4 (14/17) 64.7 (11/17) 35.7 (5/14) OLE W94 70.9 (39/55) 64.0 (16/25) 77.5 (31/40) 69.2 (9/13) 53.3 (8/15) 58.3 (7/12) Endoscopic improvement,d % (n/N) OLE W46 82.6 (57/69) 68.8 (22/32) 86.3 (44/51) 88.9 (16/18) 72.2 (13/18) 42.9 (6/14) OLE W94 73.7 (42/57) 71.4 (20/28) 78.0 (32/41) 78.6 (11/14) 62.5 (10/16) 64.3 (9/14) CS-free remission,e % (n/N) OLE W46 74.6 (47/63) 61.3 (19/31) 80.4 (37/46) 82.4 (14/17) 58.8 (10/17) 35.7 (5/14) OLE W94 69.1 (38/55) 64.0 (16/25) 75.0 (30/40) 69.2 (9/13) 53.3 (8/15) 58.3 (7/12) aClinical response: decrease from baseline in the 3-component Mayo score (sum of RBS, SFS, and MES) of ≥2 points and ≥35% and reduction of ≥1 point in RBS or an absolute RBS of ≤1 point.bClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from baseline SFS), and MES ≤1.cMet criteria for clinical response but not clinical remission.dEndoscopic improvement: MES ≤1 point. eClinical remission while off CS for ≥12 wk. MES, Mayo endoscopy subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

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