1. Litifilimab was associated with a reduction in the number of swollen and tender joints in systemic lupus erythematosus (SLE) patients as compared to a placebo.
2. Compared to placebo, litifilimab did not result in significant changes in skin-related and overall disease activity.
Evidence Rating Level: 1 (Excellent)
Study Rundown: SLE is an autoimmune disease affecting multiple organ systems. Type I interferons have been shown to contribute to the pathophysiology of SLE. Plasmacytoid dendritic cells (PDCs), a producer of type I interferons, accumulate in many affected tissues in SLE patients. Blood dendritic cell antigen 2 (BDCA2) is a negative regulator of PDC activity and a potential target for therapeutics. Notably, litifilimab is an antibody that binds and activates BDCA2, which in turn downregulates PDC immune activity. The present study is part of a two-part phase 2 trial to investigate the efficacy and safety of litifilimab, focusing on SLE patients with active arthritis and rash. The main results were derived from participants receiving either 450mg litifilimab or a placebo. Litifilimab was shown to reduce the number of swollen and tender joints from baseline more significantly than placebo. However, litifilimab did not show significant differences in secondary endpoints, measuring skin-related and global disease activity, as compared to placebo. Although the trial was small and not powered to assess secondary endpoints, its results showed the benefits of litifilimab in reducing joint-related SLE disease activity. Accordingly, further larger clinical trials must be conducted.
In-Depth [randomized control trial]: The current study was a phase 2, multicenter, double-blind, randomized, controlled trial to assess the efficacy and safety of litifilimab. Participants were included if they had SLE according to the American College of Rheumatology classification criteria, with arthritis and active skin disease. A total of 102 participants with at least four tender and four swollen joints were randomized to receive subcutaneous 450mg litifilimab or a placebo control. Exclusion criteria included certain infections, kidney disease, and concurrent immunosuppressive treatments. The primary endpoint was the change from baseline in the total number of active joints, which was a sum of swollen joints and tender joints at week 24. Secondary efficacy endpoints included skin-related disease activity response (based on Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity [CLASI-A]) and overall SLE disease activity (based on SLE Responder Index [SRI-4]) at week 24. The least-squares mean (±standard error) change from baseline to week 24 in the total number of active joints was -15.0±1.2 among litifilimab recipients and -11.6±1.3 for placebo recipients (mean difference, -3.4; 95% Confidence Interval [CI], -6.7 to -0.2; p=0.04). Nevertheless, such statistical significance was not observed in secondary endpoints, which the study authors stated the study had not been powered to evaluate. Adverse events, including diarrhea, urinary tract infection, headache, viral infections, and serious adverse events occurred at comparable rates between the two groups. Although the trial was underpowered to assess secondary endpoints, litifilimab showed benefits in reducing the number of active joints in SLE patients and phase 3 trials are currently underway to evaluate its efficacy further.
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