Efficacy and safety of litifilimab in cutaneous lupus erythematosus: 24-week results of the randomized phase 2 study, AMETHYST
In brief
Litifilimab cleared or nearly cleared skin in 15% of cutaneous lupus patients
At 16 weeks, 14.7% of participants receiving litifilimab had clear or almost clear skin, compared with 2.9% on placebo. At 24 weeks, 21.7% had at least a 70% reduction in skin disease severity, versus 5.8% on placebo; the drug was generally well tolerated, but the study was not powered to confirm differences on these secondary outcomes.
- Journal
- Journal of the American Academy of Dermatology (Q1)
- Published
- 17 October 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Joseph F Merola, Victoria P Werth, Benjamin F Chong, Filippa Nyberg, Eric F Morand, David Fivenson, et al.
- PMID
- 42892381
- DOI
- 10.1016/j.jaad.2026.10.035
Why clinicians should know about it
- Picked for Dermatology (paper of the day, 24 October 2026): Phase 2 RCT of litifilimab in cutaneous lupus erythematosus
Abstract
BACKGROUND: Cutaneous lupus erythematosus (CLE) is a serious autoimmune disease with no approved targeted treatments. OBJECTIVE: Evaluate the efficacy and safety of litifilimab in AMETHYST Part A (Phase 2). METHODS: AMETHYST is a randomized, double-blind, placebo-controlled, Phase 2/3 study that investigates litifilimab in participants with CLE. Participants were randomized to receive litifilimab 225 mg or placebo every 4 weeks during Weeks 0-24. The primary endpoint was the Cutaneous Lupus Activity Investigator's Global Assessment-Revised (CLA-IGA-R) erythema score of 0-1 at Week 16, with several Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-based endpoints at Week 24 as secondary endpoints. Safety was also assessed. RESULTS: Significantly more participants treated with litifilimab achieved clear/almost clear skin (CLA-IGA-R erythema 0-1) than those treated with placebo at Week 16 (14.7% vs 2.9%, P= .0263). Additionally, more participants treated with litifilimab achieved CLASI-70 response vs placebo at Week 24 (21.7% vs 5.8%, P = .0195). Litifilimab was generally well tolerated; safety data were consistent with prior studies. LIMITATIONS: Study was not powered to detect statistically significant differences in secondary endpoints. CONCLUSION: Litifilimab treatment led to greater improvements in skin disease activity vs placebo and was well tolerated in participants with CLE through Week 24.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.