Background/Purpose: Cenerimod is a highly selective S1P1 receptor modulator which is undergoing trials for potential therapeutic benefits in autoimmune disease, including Systemic Lupus Erythematous (SLE). The Phase 2b CARE study (NCT03742037) evaluated the efficacy and safety of cenerimod at doses 0.5, 1, 2, and 4 mg in moderate to severe SLE patients. Patients in the 0.5, 1, 2 mg, and placebo arms continued the study drug for an additional 6 months. Patients assigned to cenerimod 4 mg arm were randomly assigned (1:1) to either cenerimod 2 mg or placebo for another 6 months, designated herein as cenerimod Ex-4 mg group. All patients who had received cenerimod 4 mg for the first 6 months were included in the analysis irrespective of their treatment assignment in the next 6 months to either 2 mg or placebo. Safety outcomes were monitored for 12 months.This post-hoc analysis was performed to assess sustained responses in mSLEDAI-2K (defined as a decrease of ≥4 points from baseline for 4 consecutive monthly assessments) vs placebo over a period of 12 months.

Methods: The treatment effect was estimated for each treatment group vs placebo using a Cox proportional hazards model stratified by baseline oral corticosteroid and mSLEDAI-2K. Hazard ratios and 95% confidence interval were derived from the model. The analysis was performed over the 12-month period and the initial randomization was used as the basis for group allocation.

Results: 427 patients were randomized, 85 patients each in the 0.5, 1, and 4 mg arms and 86 patients each in the 2 mg and placebo arms. Median age was 42 years (range 18–72), 406 (95%) were female, and 337 (79%) White.A sustained response in mSLEDAI-2K score was observed in 63.5% of the patients in the cenerimod Ex-4mg group as compared to 50.0% of those in the placebo group. The median time is the time by when the event has occurred in 50% of the study subjects. The median time to the first confirmation of a 4-month sustained response in mSLEDAI-2K was estimated at 304 days in cenerimod Ex-4mg group vs 334 days in placebo group. The hazard ratio was estimated at 1.43 in cenerimod Ex-4mg group, suggesting that this group has a 43% greater chance of experiencing a 4-month sustained response in mSLEDAI-2K as compared to the placebo group (Figure 1).

Conclusion: This analysis showed that over a period of 12 months, patients in the cenerimod Ex-4 mg group were 1.43 times more likely to achieve a 4-month sustained response than those receiving placebo.The ongoing confirmatory Phase 3 program OPUS (NCT05648500 and NCT05672576) will further evaluate the safety and efficacy of 4 mg cenerimod in adults with SLE.

4-month sustained response in mSLEDAI-2K of Cenerimod ex-4 mg group as compared to the placebo

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/post-hoc-analysis-of-sustained-response-over-time-in-systemic-lupus-erythematosus-patients-treated-with-cenerimod-in-care-phase-2-b-study/