Long-term treatment of ozanimod in patients with moderate to severe ulcerative colitis
The immunosuppressive ozanimod was approved for the treatment of ulcerative colitis (UC) based on the results of the phase III clinical trial True North. An open-label study followed this and previous clinical evaluations, focusing particularly on the efficacy of long-term use of ozanimod. What insights did the subsequent monitoring bring?
Introduction
The selective immunosuppressant ozanimod reduces the number of lymphocytes in peripheral blood and suppresses their migration into the intestinal wall by modulating the sphingosine-1-phosphate (S1P) receptor. It was approved for the treatment of patients with moderately to severely active UC based on the results of the 52-week phase III True North (TN) clinical trial. The aim of the open-label extension (OLE) study following previous clinical research was to evaluate the long-term efficacy of ozanimod.
Methodology and evaluated data
Data collected for an interim analysis were examined in participants of TN who also entered OLE TN. The inclusion criteria for OLE TN in TN study participants were an inadequate response during the induction phase, loss of efficacy during the maintenance phase, or completion of maintenance therapy. Entry into OLE TN was also possible after participating in the phase II Touchstone OLE study, provided the patient completed this OLE and was treated with ozanimod 0.92 mg once daily.
In all patients who entered OLE TN from the TN study, and in a subset with a clinical response at the entry into OLE TN, clinical remission, clinical response, endoscopic improvement, and achievement of corticosteroid-free remission were evaluated at weeks 46, 94, and 142. Treatment-related adverse events were assessed from both phase II and III study data.
To supplement missing data, two methodological approaches were used – the observed case (OC) method and the non-responder imputation (NRI) method, which considers participants who terminate early as non-responders.
Results
A total of 823 patients from TN entered OLE TN by the data cutoff date (September 30, 2020), with 64% completing week 46, 34% completing week 94, and 14% completing week 142 of the follow-up therapy. The most common reason for discontinuation was insufficient efficacy (21%).
At the initiation of OLE, a total of 261 patients showed a clinical response to the therapy. The data analysis using the OC methodology indicated that the proportions of those achieving clinical remission, clinical response, endoscopic improvement, and corticosteroid-free remission remained stable over time. Compared to the overall population, treatment was more effective in patients who already showed a response at the beginning of the study. Comparable efficacy results were achieved by responders and the overall population at weeks 46 and 94.
Using the more conservative NRI methodology, the proportion of patients achieving all target parameters was predictably lower than with OC. Still, 34% of the overall patient population and 55% of the group with a present response at the onset of the study continued to show a clinical response after 94 weeks of treatment in OLE.
Conclusion
In patients with ulcerative colitis, the maintenance of clinical response to treatment was demonstrated even with long-term ozanimod administration. In the context of the OLE study, this comprised approximately an additional 2 years of therapy with this new medication. No new safety signals emerged.
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Source: Danese S., Colombel J. F., Ponich T. et al. DOP44 Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. J Crohns Colitis 2022 Jan; 16 (Suppl. 1): i093–i094, doi: 10.1093/ecco-jcc/jjab232.083.
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