Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus.

Victoria P Werth, Richard A Furie, Juanita Romero-Diaz, Sandra Navarra, Kenneth Kalunian, Ronald F van Vollenhoven, Filippa Nyberg, Benjamin H Kaffenberger, Saira Z Sheikh, Goran Radunovic, Xiaobi Huang, George Clark, Hua Carroll, Himanshu Naik, Francois Gaudreault, Adam Meyers, Catherine Barbey, Cristina Musselli, Nathalie Franchimont

Journal: The New England journal of medicine 2022;387(4):321-331

PMID: 35939578

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Abstract

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. (Funded by Biogen; LILAC ClinicalTrials.gov number, NCT02847598.).

Address: From the University of Pennsylvania and Corporal Michael J. Crescenz Veterans Affairs Medical Center - both in Philadelphia (V.P.W.); Northwell Health, Great Neck, NY (R.A.F.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubrián, Mexico City (J.R.-D.); the University of Santo Tomas, Manila, Philippines (S.N.); the University of California, San Diego, La Jolla (K.K.); Amsterdam University Medical Centers, Amsterdam (R.F.V.); Karolinska University Hospital, Stockholm (F.N.); Ohio State University, Columbus (B.H.K.); University of North Carolina at Chapel Hill, Chapel Hill (S.Z.S.); Institute of Rheumatology, University of Belgrade, Belgrade, Serbia (G.R.); Biogen, Cambridge, MA (X.H., G.C., H.C., H.N., F.G., A.M., C.M., N.F.); and Biogen, Baar, Switzerland (C.B.).

DOI: 10.1056/NEJMoa2118024