Blood dendritic cell antigen 2 (BDCA2) is a receptor that is exclusively expressed on plasmacytoid dendritic cells, which are implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied.
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 across the four groups on the basis of the primary end point, 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 widespread or severe skin involvement). Safety was also assessed.
A total of 132 participants were enrolled; 26 were assigned to the 50-mg litifilimab group, 25 to the 150-mg litifilimab group, 48 to the 450-mg litifilimab group, and 33 to the placebo group. 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 CLASI-A score at week 16 was −24.3 percentage points (95% confidence interval [CI] −43.7 to −4.9) in the 50-mg litifilimab 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. The least squares mean changes were used in the primary analysis of a best-fitting dose–response model across the three drug-dose levels and placebo, which showed a significant effect. Most of the secondary end points did not support the results of the primary analysis. Litifilimab was associated with three cases each of hypersensitivity and oral herpes infection and one case of herpes zoster 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 with regard to a measure of skin disease activity over a period of 16 weeks. Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.)
Funding and Disclosures
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
We thank Sachin Sobale, Parul Galuti, and Jianjun Liu for their contributions to the statistical analyses; the trial coordinators, staff, and participants for their contributions to the trial; and Gabrielle Knafler and Meryl Mandle, of Excel Scientific Solutions, and Jessica Gamage and Sara Henriques, of Selene Medical Communications, for writing and editorial assistance with earlier versions of the manuscript.
Print Subscriber? Activate your online access.