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Treatment with an investigational drug targeting the blood dendritic cell antigen 2 (BDCA2) receptor reduced skin disease activity in patients with cutaneous lupus erythematosus, the phase II LILAC study showed.

In patients with active cutaneous lupus erythematosus with or without systemic lupus erythematosus (SLE) manifestations, baseline scores on the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity scale (CLASI-A) were significantly reduced at week 16 with litifilimab versus placebo across the three doses tested:

• 50-mg litifilimab group: -24.3 percentage points (95% CI -43.7 to -4.9)
• 150-mg litifilimab group: -33.4 percentage points (95% CI -52.7 to -14.1)
• 450-mg litifilimab group: -28.0 percentage points (95% CI-44.6 to -11.4)

However, most secondary endpoints in the study -- which primarily included patients with moderate-to-severe disease at baseline -- did not support the results of the primary analysis, according to Nathalie Franchimont, MD, PhD, of drug developer Biogen in Cambridge, Massachusetts, and colleagues.

Larger and longer trials are necessary to further evaluate the efficacy and safety of the drug in patients with cutaneous lupus erythematosus, the authors acknowledged in the .

Joan Von Feldt, MD, MSEd, a professor emeritus at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, called the results "encouraging" and said CLASI-A has been validated as a measure of the degree of severity of "lupus skin."

"It is frustrating that only 10% of the participants were Black or of African descent," added Von Feldt, who was not involved in the research. "This ethnic group continues to be underrepresented in clinical trials and the results may not be generalizable to this population."

Serious adverse events (SAEs) in the study included hypersensitivity skin reactions, and herpes infections (oral and herpes zoster). One case of herpes zoster meningitis occurred in a patient in the 50-mg litifilimab group, 4 months after receiving the final dose.

Von Feldt explained that litifilimab binds to BDCA2, "a receptor solely expressed on the surface of plasmacytoid dendritic cells, and inhibits type I interferon, and other cytokines/chemokines."

"Inhibiting type I interferon has been associated with an increased risk of viral infections, and specifically herpes infections," she continued. "Therefore, although the SAEs are not surprising, it may influence decisions by clinicians and patients as to whether to choose this therapy if it does become commercially available."

Development of litifilimab in lupus continues. The phase III TOPAZ-1 trial, for example, is currently recruiting patients with active SLE at multiple sites around the world, and seeks to demonstrate the efficacy of litifilimab compared with placebo in participants receiving standard background lupus therapy. The primary outcome measure is the percentage of participants who achieve a level 4 response on the SLE Responder Index (SRI-4) at week 52.

The current phase II trial enrolled 132 participants with active histologically confirmed cutaneous lupus erythematosus with or without SLE and randomized them to either placebo (n=33) or litifilimab at doses of 50 mg (n=26), 150 mg (n=25), or 450 mg (n=48). Participants in the study were receiving additional treatments, including glucocorticoids, hydroxychloroquine, and immunosuppressive drugs.

The investigators used the least squares mean (LSM) changes in the primary analysis of a best-fitting dose-response model across the three drug-dose levels and placebo.

At baseline, mean CLASI-A scores were 15.2 in the 50-mg litifilimab group, 18.4 in the 150-mg litifilimab group, 16.5 in the 450-mg litifilimab group, and 16.5 in the placebo group.

At 16 weeks, LSM changes from baseline were -38.8 percentage points, -47.9 percentage points, and -42.5 percentage points, respectively, for the three litifilimab groups, and -14.5 percentage points for the placebo group.

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