EFFECT OF CENERIMOD, AN S1P1 MODULATOR, ON FATIGUE IN SLE: RESULTS FROM THE PHASE 2 CARE STUDY

PV171 / #456 Poster Topic: AS19 - Patient-Reported Outcome Measures Background/Purpose Cenerimod is an investigational highly selective S1P 1 receptor modulator with potential therapeutic benefits in autoimmune disease. 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 systemic lupus erythematosus (SLE) patients. Cenerimod had a significant effect on the primary endpoint, the change from baseline to month 6 in modified SLE disease activity index-2000 score (mSLEDAI 2K, which excludes leukopenia). The largest difference vs placebo was observed with 4 mg (-4.04 vs -2.85 from baseline) with a least square mean difference vs placebo of -1.19 (P=0.029). In the subgroup of patients with high IFN-1 gene expression (approx. 50% of the population), 4 mg showed a greater treatment effect vs placebo (-5.41 vs -2.62, P=0.0015). Based on these results, cenerimod 4 mg is selected for the ongoing phase 3 OPUS program ( NCT05648500 , NCT05672576 ). Fatigue, reported by 67% to 90% of SLE patients,[1] is often the most bothersome symptom, impairing health-related quality of life. This outcome was measured in the CARE study, and the results of these analyses, focusing on patients treated with 4 mg (both the whole group and the IFN-1-high subgroup), are presented in this abstract. Methods Phase 2b CARE study was a multicenter, randomized, double-blind, placebo-controlled trial in which patients received once-daily oral cenerimod (1 of 4 doses) or placebo, in addition to stable background SLE therapy, for 6 months. The fatigue scores were collected using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale score, and the fatigue component of the Lupus Quality of Life (QoL) questionnaire. Observed changes from baseline to month 6 were analyzed descriptively using the full analysis set. Results A total of 427 patients were randomized in the CARE study, with 85 patients each in the 0.5 mg,1 mg, and 4 mg arms and 86 patients in the 2 mg and placebo arms. The median age was 42 years (range 18-72); 406 (95%) patients were female, and 337 (79%) were White. In the overall study population, an increase in FACIT-Fatigue score, indicating improved fatigue, was observed in all treatment groups at month 6, with no dose-dependent trends. The median (IQR) change from baseline was 3 (0, 8) in the cenerimod 4 mg arm and 2 (-1.79, 9) in the placebo arm. In the subgroup analysis of patients with high IFN-1 gene expression, the median (IQR) change from baseline was much better in the 4 mg arm, 5 (1, 9.5), than in the placebo arm, 1 (-5.33, 6) (Table 1). The results from the Lupus QoL fatigue scores (higher scores also indicate improved fatigue) showed similar trends. The median (IQR) change from baseline was 12.5 (0, 18.75) in the 4 mg arm and 3.125 (-6.25, 18.75) in the placebo arm in overall population. The 4 mg group exhibited a greater median (IQR) change of 15.63 (3.13, 25) compared to placebo 0 (-9.38, 12.5) in the high IFN-1 gene expression subgroup (Table 2). Table 1: FACIT-Fatigue: observed value at baseline and chance from baseline at Month 6 Table 2: Lupus Qol-Fatigue component: observed value at baseline and change from baseline at Month 6 Conclusions Improvements in mSLEDAI-2K scores in SLE patients treated with cenerimod 4 mg for 6 months were paralleled by relevant improvements in fatigue scores compared to placebo in the subgroup of patients with high IFN-1 gene expression. References: [1.] Cornet A. Lupus Sci Med 2021;8(1):e000469.

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