In the 48-week, phase II PAISLEY trial published in Lupus Science & Medicine, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, showed meaningful improvements in patient-reported outcomes among individuals with active systemic lupus erythematosus (SLE). The study enrolled 363 patients who were randomised to receive a placebo or varying doses of deucravacitinib.
By week 48, patients receiving deucravacitinib reported greater reductions in pain and fatigue compared with those on placebo. Specifically, pain scores improved by 2.2–2.3 points in the deucravacitinib arms versus 1.3 points in the placebo group. Fatigue scores decreased by 5.9–7.3 points in the active treatment groups compared with 3.4 points with placebo. Regardless of treatment group, SRI-4 and BICLA responders reported greater improvements in pain and fatigue than non-responders. Deucravacitinib-treated patients also had higher SRI-4 and BICLA response rates. Deucravacitinib-treated patients also demonstrated superior health-related quality-of-life scores. The mean SF-36 physical component scores reached ≥44.6 in the deucravacitinib groups versus 41.5 with placebo, and mental component scores were ≥46.3 compared to 45.2 in the placebo group. A greater proportion of patients in the treatment arms achieved clinically meaningful gains in SF-36 metrics.
Deucravacitinib is a first-in-class, oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2), approved in several countries for the treatment of adults with moderate to severe plaque psoriasis. Unlike Janus kinase (JAK) 1, 2, and 3 inhibitors, deucravacitinib uniquely targets TYK2, blocking the signaling pathways of type I interferons, interleukin (IL)-12, and IL-23—cytokines that play a central role in the pathogenesis of various autoimmune diseases, including SLE. A systematic review and network meta-analysis by Bokor et al. evaluated the efficacy and safety of novel systemic therapies in cutaneous lupus erythematosus (CLE) across 53 studies. Deucravacitinib demonstrated the highest efficacy in achieving CLASI-50 (OR: 8.28) compared to placebo, followed by litifilimab (OR: 2.54) and anifrolumab (OR: 2.25). No significant differences in adverse events or serious adverse events were found between these therapies and placebo. Deucravacitinib showed superior efficacy and safety compared to anifrolumab, indicating its potential role in patients with CLE unresponsive to standard treatments.
These findings supported further investigation in phase III trials and highlighted that meaningful patient-reported benefits can occur even in the absence of a full clinical response. Deucravacitinib continues to show promise as a novel therapeutic option for managing symptoms and enhancing quality of life in patients with active SLE.
References
- Mosca M, Arnaud L, Askanase A, Hobar C, Becker B, Singhal S, Banerjee S, Pomponi S, Choi J, Strand V. Deucravacitinib, an oral, selective, allosteric, tyrosine kinase 2 inhibitor, in patients with active SLE: efficacy on patient-reported outcomes in a phase II randomised trial. Lupus Sci Med. 2025 Jun 1;12(1):e001517.
- Bokor LA, Martyin K, Krebs M, Galajda NÁ, Meznerics FA, Szabó B, Hegyi P, Lőrincz K, Kiss N, Bánvölgyi A, Hidvégi B. Deucravacitinib shows superior efficacy and safety in cutaneous lupus erythematosus compared to various biologics and small molecules – A systematic review and meta-analysis. Autoimmun Rev. 2025 Feb 28;24(3):103723.