2440: Effect of Cenerimod on Four Main Clinical Items of SLEDAI-2K Score in SLE Patients in a Phase 2b Study

Background/Purpose: Cenerimod is a selective S1P₁ receptor modulator that has the potential to reduce the abnormal immune response seen in Systemic lupus erythematosus (SLE) thereby leading to decreased disease activity and improved clinical outcomes for patients.

In a recent multicenter, randomized, double-blind, placebo-controlled phase 2b trial (CARE study, NCT03742037), the efficacy, safety, and tolerability of four doses of cenerimod (0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to placebo in adults with moderate-to-severe SLE who were receiving standard of care background therapy. The primary endpoint was the change from baseline in mSLEDAI-2K scores from baseline to month 6. Cenerimod 4 mg is currently being investigated for the treatment of SLE in two 1-year treatment phase 3 trials (NCT05648500 and NCT05672576).

This post-hoc analysis of the CARE study was performed to compare the monthly changes (improvements) in four individual SLEDAI-2K items from baseline over 6 months between cenerimod 4 mg and placebo. These four main clinical items are: arthritis, rash, alopecia, and mucosal ulcers that are clinically significant manifestations of SLE. Arthritis affects around 82.6% of patients, rash is seen in approximately 69.2% of patients, alopecia affects about 58.2% of patients and mucosal ulcers occur in about 32.5% of patients.

Methods: The SLEDAI-2K values were measured on a monthly basis. Proportions of patients with each of the four selected SLEDAI-2K items improvements were calculated by treatment group and visit only for the cenerimod 4 mg and the placebo arm. Improvement was defined as a reduction vs baseline score.

Results: At baseline, involvement of individual SLEDAI-2K items was well balanced between cenerimod 4 mg and placebo arm. Numeric treatment differences ≥10% favoring cenerimod 4 mg were seen at months 4-6 for alopecia and months 2–6 (except month 3 which showed improvement of ≥5%) for mucosal ulcers. (Table 1).

Conclusion: This post-hoc analysis provided insights to the trends in improvements of four individual SLEDAI-2K clinical components when patients were treated with cenerimod 4 mg dose for 6 months. There was no obvious difference in arthritis or rash scores vs placebo. However, as compared to placebo, better early improvement was seen in alopecia (from month 4) and mucosal ulcers (from month 4) until month 6. 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.