TY - JOUR
T1 - Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus
AU - Werth, Victoria P.
AU - Furie, Richard A.
AU - Romero-Diaz, Juanita
AU - Navarra, Sandra
AU - Kalunian, Kenneth
AU - van Vollenhoven, Ronald F.
AU - Nyberg, Filippa
AU - Kaffenberger, Benjamin H.
AU - Sheikh, Saira Z.
AU - Radunovic, Goran
AU - Huang, Xiaobi
AU - Clark, George
AU - Carroll, Hua
AU - Naik, Himanshu
AU - Gaudreault, Francois
AU - Meyers, Adam
AU - the LILAC Trial Investigators
AU - Barbey, Catherine
AU - Musselli, Cristina
AU - Franchimont, Nathalie
N1 - Funding Information: Supported by Biogen. Publisher Copyright: Copyright © 2022 Massachusetts Medical Society.
PY - 2022/7/28
Y1 - 2022/7/28
N2 - BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
AB - BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
UR - http://www.scopus.com/inward/record.url?scp=85135406392&partnerID=8YFLogxK
U2 - https://doi.org/10.1056/NEJMoa2118024
DO - https://doi.org/10.1056/NEJMoa2118024
M3 - Article
C2 - 35939578
SN - 0028-4793
VL - 387
SP - 321
EP - 3313
JO - New England journal of medicine
JF - New England journal of medicine
IS - 4
ER -