Deucravacitinib improves cutaneous lupus erythematosus activity

Key takeaways:

• Deucravacitinib inhibits tyrosine kinase 2, which is implicated in cutaneous lupus erythematosus’s pathophysiology.
• Deucravacitinib yielded improvements in disease severity by week 16.

ORLANDO — Twice-daily deucravacitinib 3 mg and 6 mg significantly improved cutaneous lupus erythematosus activity by week 16, according to a presenter at the American Academy of Dermatology Annual Meeting.

“[Tyrosine kinase (TYK)]-2 is an important mediator of cytokine signaling and has effects on type 1 and 3 interferons, [interleukin (IL)]-23 and IL-12 ... and it’s involved in immune-specific responses,” Victoria P. Werth, MD, professor of dermatology at the Hospital of the University of Pennsylvania and chief of dermatology at the Philadelphia VA Hospital, said during the late-breaking session.

“TYK-2 and types 1 and 3 interferon are known to be involved in [cutaneous lupus erythematosus (CLE)] pathophysiology,” Werth continued.

Deucravacitinib is an oral, selective, allosteric TYK-2 inhibitor that is approved for the treatment of moderate to severe plaque psoriasis in the U.S. and other countries and is under investigation for the treatment of systemic lupus erythematosus (SLE), psoriatic arthritis and Sjögren’s disease.

Werth presented findings from the 52-week, phase 2 PAISLEY CLE trial, in which deucravacitinib is being evaluated for the treatment of CLE. In the trial, 74 adults were randomly assigned to receive deucravacitinib 3 mg (n = 25), deucravacitinib 6 mg (n = 25) or placebo (n = 24) twice daily. A total of four, four and two patients discontinued treatment in the respective groups.

The baseline CLE Disease Area and Severity Index activity (CLASI-A) scores were 18.1, 14.8 and 16 in the deucravacitinib 3 mg, 6 mg and placebo groups, respectively. A total of 80%, 72% and 79.2% of patients in the respective groups had severity scores greater than 10.

Werth presented results through week 16 which showed that patients treated with deucravacitinib 3 mg and 6 mg achieved significantly greater reductions in their CLASI-A scores from baseline than those treated with placebo (47.5% and 50%, respectively vs. 28.4%).

The deucravacitinib 3 mg and 6 mg groups experienced an adjusted mean CLASI-A score change from baseline of –9.3 and –8.7, respectively, whereas the placebo group saw a –5.3 change.

By week 16, 56.7% and 52.3% of the 3 mg and 6 mg deucravacitinib groups achieved a 50% improvement of their CLE compared with 19% of the placebo group.

According to Werth, deucravacitinib was well tolerated with adverse events occurring in 68%, 79.2% and 50% of the 3 mg, 6 mg and placebo groups, respectively. Two serious events occurred in each deucravacitinib group, and one occurred in the placebo group. None of the events led to discontinuation.

“These data support the further evaluation of deucravacitinib for the treatment of cutaneous manifestations of lupus, including patients with SLE in the ongoing SLE trials,” Werth concluded.