P1009 Efficacy and safety of 4 years of continuous ozanimod treatment: an interim analysis of the True North open-label extension study

Abstract

Abstract Background The phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod (OZA) over 52 wk in patients (pts) with moderately to severely active ulcerative colitis (UC); the ongoing TN open-label extension (OLE) is assessing long-term efficacy and safety. This interim analysis of the TN OLE assessed pts with up to ~4 y of continuous OZA treatment. Methods Clinical responders after 52 wk of continuous OZA treatment (0.92 mg/d) during TN who subsequently entered the TN OLE were included in this analysis. Data were analysed up to OLE Week (W) 142, representing up to ~4 y of continuous OZA treatment. Symptomatic response (≥1-point and ≥30% decrease from baseline [BL] in the combined 6-point rectal bleeding subscore [RBS] + stool frequency subscore [SFS] and ≥1-point decrease in RBS or absolute RBS ≤1) and symptomatic remission (RBS=0 and SFS ≤1 [and ≥1-point decrease from BL SFS]) were evaluated from OLE W5 through OLE W142. Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at OLE W46, W94, and W142. Endpoints were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses. Adverse events were monitored throughout TN and the OLE. Results In all, 131 pts entered the OLE after achieving clinical response on OZA at W52 in TN. At the data cutoff, 87.0% of pts completed OLE W46, 71.8% completed OLE W94, and 64.1% completed OLE W142. Most (67.9%) pts had left-sided UC disease, 23.7% had concomitant CS use at TN BL, and 32.1% had prior exposure to tumour necrosis factor inhibitors. Symptomatic response and symptomatic remission were observed in 100.0% and 84.4% of pts, respectively, at OLE W5 in the OC analysis (93.1% and 78.6%, respectively, in the NRI analysis). By OLE W142, symptomatic response and symptomatic remission rates were 98.7% and 88.3%, respectively, in the OC analysis and 58.0% and 51.9%, respectively, in the NRI analysis. Rates of clinical and endoscopic endpoints during the OLE are shown in Figure 1A (OC) and 1B (NRI). Of note, 65.3% of TN W52 clinical responders achieved clinical remission and CS-free remission at OLE W142 in the OC analysis (35.9% in the NRI analysis). With this additional year of follow-up in the OLE, there were no new cases of bradycardia, third-degree atrioventricular block, hypertension, herpes zoster, or macular oedema, and no clinically meaningful change in malignancy exposure-adjusted incidence rates (Table). No serious hepatic events occurred. Conclusion Clinical responders after 1 y on OZA sustained response for an additional 3 y and achieved clinical remission with continuous OZA exposure. OZA is a safe, tolerable, and durable therapy for pts with UC.