NEJM: Therapeutic effect of anti-BDCA2 antibody Litifilimab on systemic lupus erythematosus (LILAC study)

Litifilimab ( an anti-BDCA2 humanized monoclonal antibody ) is a subcutaneously administered humanized IgG1 monoclonal antibody that binds to BDCA2 to downregulate the production

The efficacy and safety

This study evaluating the efficacy of BIIB059 in subjects with systemic lupus erythematosus and active skin manifestations, as well as subjects with lupus erythematosus (LILAC), a phase 2, multicenter, double-blind, randomized, controlled trial evaluating the efficacy and safety

Research methodology

Screening of adults ages 18 to 75 in accordance with the 1997 American Academy of Rheumatology SLE Classification Criteria

Part A of the trial was conducted

Participants enrolled according to version 1 of the protocol had active skin diseases

Based on the protocol 2nd and subsequent versions, after a screening period of 28 days, we assigned participants in a 1:1 ratio using an interactive response system and stratified based on oral glucocorticoid dose (≤ 10 mg vs.

The primary endpoint (initially the percentage change in clasi-A score relative to baseline at week 12) was changed in the revised protocol to a change in the total number of active joints relative to baseline at week 24 (defined as a swollen joint and a 28 joint score based on DAS

The secondary efficacy endpoint for assessing skin-related disease activity was a decrease of at least 50% from baseline in the CLASI-A score (CLASI-50 response) at week 24; Percentage change in CLASI-A score relative to baseline at weeks 12 (original primary endpoint), week 16, and week 24; At week 24, the CLASI-A score drops by at least 4 and 7 points

At week 24, change in overall SLE disease activity was measured as a secondary endpoint

Research results

The trial was conducted

Table 1 Characteristics of baseline participants

The demographic and disease characteristics of the two groups were substantially similar at baseline (table 1), with the exception of the litifilimab group, which had a higher proportion of female participants (98% in the litifilimab group vs 88%

Main finish line

The mean (± SD) total number of movable joints at primary endpoints in the 450 mg litifilimab and placebo groups were 19.

Secondary endpoint

For all secondary endpoints except one secondary endpoint associated with skin-related disease activity, including the original primary endpoint for the change in CLASI-A score from baseline, the 95% confidence interval for the difference between groups included zero (Table 2 and S7

For secondary endpoints associated with SLE disease activity, at week 24, 36 participants (56%) were observed in the litifilimab group responded to SRI-4 and 16 participants (29%) in the placebo group (least squares mean difference, 26.

security

Adverse events occurred in 45 participants (59%) in the combined litifilimab group and 38 participants (68%) in the placebo group (table 3
).
Most adverse events were mild or moderate, and trial investigators rated
them based on the severity definition included in the trial protocol.
The most commonly reported adverse events (≥5% of participants in the combined litifilimab group) were diarrhea, nasopharyngitis, urinary tract infections, falls, and headaches
.
The litifilizumab group reported influenza virus infection (3 cases), herpes zoster virus infection (2 cases), herpetic keratitis (1 case) and viral gastroenteritis (1 case); Herpes zoster and influenza (2 cases each) were observed in the placebo group (table 3 and S18).

Conclusions of the study

During the 24-week period, Litifilimab administered at a dose of 450 mg decreased the number of swelling and tender joints compared to baseline
.
Larger and longer trials are needed to determine the efficacy and safety
of litifilimab in patients with SLE.

References:

Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus.
N Engl J Med 2022; 387:894-904 DOI: 10.
1056/NEJMoa2118025