Blood dendritic cell antigen 2 (BDCA2) is a receptor exclusively expressed on plasmacytoid dendritic cells, implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be effective in reducing disease activity in patients with cutaneous lupus erythematosus has not been thoroughly studied.
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In this phase 2 trial, we randomly assigned adults with histologically confirmed cutaneous lupus erythematosus with or without systemic manifestations in a 1:1:1:1 ratio to receive subcutaneous litifilimab (at a dose of 50, 150 or 450 mg) or placebo at weeks 0, 2, 4, 8 and 12. We used a dose-response model to assess whether there was a response in the four groups based on the primary endpoint , which was the percent change from baseline to 16 weeks in the Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity score (CLASI-A; scores range from 0 to 70, with higher scores indicating more extensive skin involvement or more serious). Safety was also assessed.
A total of 132 participants were registered; 26 were allocated to the litifilimab 50 mg group, 25 to the litifilimab 150 mg group, 48 to the litifilimab 450 mg group and 33 to the placebo group. The mean CLASI-A scores for the groups at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. The difference from placebo in the change from baseline in the CLASI-A score at week 16 was -24.3 percentage points (95% confidence interval [CI] −43.7 to −4.9) in the litifilimab 50 mg group, −33.4 percentage points (95% CI, −52.7 to −14.1) in the 150 mg group, and −28 .0 percentage points (95% CI, −44.6 to −11.4) in the 450 mg group. Least-squares mean changes were used in the main analysis of a best-fit dose-response model for all three drug dose levels and placebo, which showed a significant effect. Most of the secondary endpoints did not support the results of the primary analysis. Litifilimab has been associated with three cases each of hypersensitivity and oral herpes infection and one case of shingles infection. One case of herpes zoster meningitis occurred 4 months after the participant received the last dose of litifilimab.
In a phase 2 trial involving participants with cutaneous lupus erythematosus, treatment with litifilimab was superior to placebo on a measure of skin disease activity over a 16-week period. Larger and longer trials are needed to determine the effect and safety of litifilimab in the treatment of cutaneous lupus erythematosus. (Funded by Biogen; ClinicalTrials.gov LILAC number, NCT02847598.)