Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension

Abstract

Backgrounds and aims: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis.

Methods: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates.

Results: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently.

Conclusions: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Keywords: S1P receptor modulator; Ulcerative colitis; ozanimod.

Graphical Abstract

Figure 1

Proportions of patients on continuous ozanimod who entered the OLE in clinical response achieving symptomatic clinical response and symptomatic clinical remission over time in the OLE through OLE Week 94. [A, B] OC analysis. [C, D] NRI analysis. Denominators for the OC analyses were based on the numbers of patients who completed OLE Week 5, 10, 16, 22, 34, 46, 58, 70, 82, or 94 and had data available for the endpoints in question. Denominators for the NRI analyses were based on the numbers of patients who completed OLE Week 5, 10, 16, 22, 34, 46, 58, 70, 82, or 94, or discontinued ozanimod treatment. ^aSymptomatic clinical response was defined as a decrease from baseline in the combined 6-point RBS + SFS of ≥1 point and ≥30%, and a decrease of ≥1 point in RBS or an absolute RBS ≤1 point. ^bSymptomatic clinical remission was defined as an RBS = 0 and SFS ≤1, and a decrease of ≥1 point from the baseline SFS. ^cAll patients received 52 weeks of ozanimod treatment before entering the OLE. NRI, nonresponder imputation; OC, observed case; OLE, open-label extension; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

Figure 2

Clinical outcomes [ie, clinical remission, clinical response, and corticosteroid-free remission] at OLE Weeks 46 and 94 in patients on continuous ozanimod who entered the OLE in clinical response. [A] OC analysis. [B] NRI analysis. Denominators for the OC analyses were based on the numbers of patients who completed OLE Week 46 or 94 and had data available for the endpoints in question. Denominators for the NRI analyses were based on the numbers of patients who completed OLE Week 46, completed OLE Week 94, or discontinued ozanimod treatment. ^aClinical remission is defined as an RBS = 0 point and an SFS ≤1 point [and a decrease of ≥1 point from the baseline SFS] and an endoscopy subscore ≤1 point. ^bClinical response is defined as a reduction from baseline in the 3-component Mayo score [sum of the RBS, SFS, and endoscopy subscore] of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of ≤1 point. ^cCorticosteroid-free remission is defined as clinical remission while off corticosteroids for ≥12 weeks. NRI, nonresponder imputation; OC, observed case; OLE, open-label extension; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

Figure 3

Objective outcomes [ie, endoscopic improvement, mucosal healing, and histological remission] at OLE Weeks 46 and 94 in patients on continuous ozanimod who entered the OLE in clinical response. [A] OC analysis. [B] NRI analysis. Denominators for the OC analyses were based on the numbers of patients who completed OLE Week 46 or 94 and had data available for the endpoints in question. Denominators for the NRI analyses were based on the numbers of patients who completed OLE Week 46, completed OLE Week 94, or discontinued ozanimod treatment. ^aEndoscopic improvement is defined as an endoscopy subscore of ≤1 point. ^bHistological remission is defined as a Geboes score of <2.0. ^cMucosal healing is defined as an endoscopy score of ≤1 point and a Geboes score of <2.0. ^dThree patients at OLE Week 46 and 34 patients at OLE Week 94 did not have histology data available at data cutoff and are therefore not included in the denominator for histological remission and mucosal healing. NRI, nonresponder imputation; OC, observed case; OLE, open-label extension.