Litifilimab Anti-BDCA2 Antibody Trial for Systemic Lupus Erythematosus
Antibody binding of blood dendritic cell antigen 2 (BDCA2), which is expressed exclusively on plasmacytoid dendritic cells, suppresses the production of type I interferon implicated in the pathogenesis of systemic lupus erythematosus (SLE). The safety and efficacy of subcutaneous litifilimab, a humanized monoclonal antibody that binds to BDCA2, in patients with SLE has not been widely studied.
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We conducted a phase 2 trial of litifilimab involving participants with SLE. The initial trial design was to randomly assign participants to receive litifilimab (at a dose of 50, 150 or 450 mg) or placebo administered subcutaneously at weeks 0, 2, 4 , 8, 12, 16, and 20, with the main end point for assessment of cutaneous lupus activity. The trial design was then modified; adults with SLE, arthritis, and active dermatosis were randomly assigned to receive either litifilimab at a dose of 450 mg or placebo. The revised primary endpoint was change from baseline in total active joint count (defined as the sum of swollen joints and tender joints) at week 24. Secondary endpoints were changes in cutaneous and global disease activity. Safety was also assessed.
A total of 334 adults were assessed for eligibility and 132 were randomized (64 received 450 mg litifilimab, 6 received 150 mg litifilimab, 6 received 50 mg litifilimab, and 56 received placebo). The main analysis was conducted on the 102 participants who had received 450 mg of litifilimab or a placebo and who had at least four painful joints and at least four swollen joints. The mean (±SD) baseline number of active joints was 19.0±8.4 in the litifilimab group and 21.6±8.5 in the placebo group. The least squares mean (±SD) change from baseline to Week 24 in total active joint count was -15.0±1.2 with litifilimab and -11.6±1.3 with placebo (mean difference, -3.4; 95% confidence interval, -6.7 to –0.2; P=0.04). Most of the secondary endpoints did not support the results of the primary endpoint analysis. Receiving litifilimab was associated with adverse events, including two cases of herpes zoster and one case of herpetic keratitis.
In a phase 2 trial involving participants with SLE, litifilimab was associated with a greater reduction from baseline in the number of swollen and tender joints than placebo over a 24-week period. Longer and larger trials are needed to determine the safety and effectiveness of litifilimab for the treatment of SLE. (Funded by Biogen; ClinicalTrials.gov LILAC number, NCT02847598.)