Litifilimab superior to placebo in reducing tender, swollen joints in lupus
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Litifilimab is superior to placebo in reducing tender and swollen joints among patients with systemic lupus erythematosus, according to phase 2 trial data published in the New England Journal of Medicine.
“Litifilimab is a subcutaneously administered, humanized IgG1 monoclonal antibody that binds BDCA2, resulting in the down-regulation of type I interferon, cytokine, and chemokine production,” Richard A. Furie, MD, chief of rheumatology at Northwell Health in New York, and co-authors wrote. “In a phase 1 trial that included 12 participants with SLE and cutaneous lupus erythematosus, biologic activity of litifilimab was shown by a dampened interferon signature in blood and modulated type I interferon–induced proteins in skin.
“Here, we report the findings from part A [of the phase 2 trial], which involved participants with SLE who had both active arthritis and rash,” they added. “Part B, which focused on cutaneous lupus erythematosus with or without systemic manifestations, has been reported previously.”
To investigate the safety and efficacy of litifilimab (BIIB059, Biogen) in patients with SLE, Furie and colleagues conducted the LILAC trial, a phase 2, two-part, multicenter, double-blind, randomized, controlled study. The trial included patients between the ages of 18 and 75 years who had SLE according to the 1997 American College of Rheumatology classification criteria. Patients were required to have the diagnosis in writing 24 weeks before agreeing to participate in the trial.
Included patients were also required to demonstrate antinuclear antibody (ANA) titers of 1:80 or greater, anti-double-stranded DNA antibody levels of 30 IU per mL, or both. In addition, patients were allowed to enroll while receiving prednisone in doses of less than 20 mg per day.
The trial included two distinct protocols for enrollment. The first protocol allowed patients with active skin disease at the time of screening and randomization. Protocol two, meanwhile, included patients with one or more active skin lesions, as well as active arthritis. Under the first protocol, patients were randomized 1:1:1:1, but the trial was reconfigured before unblinding took place in part to slow recruitment, the authors wrote.
In protocol two, patients were randomized 1:1 following a 28-day screening process. Patients in this protocol received litifilimab 450 mg or placebo at weeks 0, 2, 4, 8, 12, 16 and 20. Following the 24-week dosing period, patients were followed for a 12-week safety observation period.
Following the protocol change, the primary endpoint was the change from baseline in the total number of active joints at week 24. Secondary endpoints included a decrease of 50% or more from baseline in skin-related disease activity. Overall changes in SLE disease activity were included as an additional secondary endpoint. The researchers monitored adverse events, serious adverse events and changes in laboratory numbers.
In total, the study included 132 patients, of whom 64 were treated with litifilimab 450 mg, six received litifilimab 150 mg, six received litifilimab 50 mg and 56 received placebo. The analysis, however, only included the patients who received litifilimab 450 mg or placebo, the authors wrote.
According to the researchers, the least-squares mean change from baseline to week 24, as measured by the total number of active joints, was –15.0±1.2 with litifilimab and –11.6±1.3 in the placebo group (mean difference = –3.4; 95% CI, –6.7 to –0.2). Regarding safety, litifilimab was associated more commonly with adverse events, including two cases of herpes zoster and one case of herpes keratitis, the authors wrote.
“In this phase 2, randomized, placebo-controlled trial that involved participants with SLE, arthritis, and active skin disease, litifilimab at a dose of 450 mg was superior to placebo in the change from baseline in the total number of active joints at week 24,” Furie and colleagues wrote. “Larger and longer trials are necessary to determine the effect and safety of litifilimab in patients with SLE.”
Reference:
Furie R, et al. J Clin Invest. 2019;doi:10.1172/JCI124466.