Phase II Data Shows Litifilimab’s Treatment Potential for CLE | Latest news for doctors, nurses and pharmacists

In part B* of the in two parts 16-week LILAC study, anti-BDCA2**
antibody litifilimab reduced skin disease activity in people with cutaneous lupus erythematosus (CLE).

CLE causes irreversible damage and disfigurement, impairs patients’ quality of life, and is associated with depression, anxiety, and fatigue,” the researchers said. Topical glucocorticoids and antimalarial drugs are considered first-line treatment options for CLE. However, there is insufficient evidence supporting the benefit of glucocorticoids; with antimalarials, responses were inconsistent. [J Eur Acad Dermatol Venereol 2017;31:389-404;
Br J Dermatol 2017;177:188-196; Cochrane Database Syst Rev 2021;3:CD007478]

“This phase II trial involving participants with active, histologically confirmed CLE with or without manifestations [of
systemic lupus erythematosus (SLE)] showed a significant dose-response relationship for the primary endpoint of the CLASI-A*** score, a measure of skin disease activity, over a 16-week period,” the researchers said.

Part B of LILAC included 132 participants with moderate to severe subacute#
or chronic## KEY (or both). They were randomized to receive litifilimab SC 50, 150, or 450 mg (n=26, 25, and 48, respectively) or placebo (n=33) at weeks 0, 2, 4, 8, and 12.
Eligible participants had also received prior treatment with topical or antimalarial agents (or both) that failed or made side effects intolerable. [N Engl J Med
2022;387:321-331]

Mean baseline CLASI-A scores were 15.2, 18.4, 16.5, and 16.5 for the litifilimab 50, 150, and 450 mg and placebo arms, respectively.

At week 16, baseline CLASI-A scores fell in all arms, more so with litifilimab (least squares mean [LSM] changes,
-38.8, -47.9, and -42.5% with 50, 150, and 450 mg doses, respectively) than with the placebo (change in LSM,
–14.5%). “[The] negative values ​​indicate improvement from baseline,” the researchers noted.
Using the best-fit dose-response model, these were found to be significant.

Between litifilimab and placebo, the LSM differences in CLASI-A score changes from baseline to week 16 were -24.3, -33.4, and -28.0 percentage points for the respective 50 doses. , 150 and 450 mg. However, the summary dose-response analysis did not compare the three doses to each other.

Three cases of hypersensitivity have been reported with litifilimab, leading to discontinuation of treatment. Viral infections have also been reported with the use of litifilimab [though unspecified]; flu, oral herpes, shingles, upper respiratory tract infection, rash).

Seven litifilimab recipients experienced serious adverse events, two had SLE flares (with litifilimab 150 mg) and one had a severe case of herpes zoster meningitis (with litifilimab 50 mg) approximately 4 months after receiving the last dose .

“The high rate of shingles among the participants underscores the importance of giving patients the shingles vaccine before starting these medications,”
said
Doctor Daniel Wallace of Cedars-Sinai Medical Center, Los Angeles, California, USA, in an accompanying editorial.
[N Engl J Med 2022;387:939-940]

Alteration of upstream lupus inflammatory pathways

“[The findings] and the subsequent FDA approval of anifrolumab, a monoclonal antibody that binds to and internalizes the type I interferon receptor, for the treatment of SLE, suggest the possibilities of altering pathways upstream of the system innate immune system, Wallace noted.

CLASI-A score improvements with litifilimab reported in LILAC
surpassed those seen in previous reports. However, direct comparisons between the studies cannot be made because they had different patient populations, Wallace pointed out.

“The results are nonetheless all provocative for phase II trials…Lupus has lagged behind its rheumatic disease cousins, such as vasculitis and rheumatoid arthritis, in drug development,” said noted Wallace. “The findings…encourage further exploration of interventions that affect lupus inflammatory pathways upstream in the lupus innate immune system.”

Larger and longer trials are warranted to validate the efficacy and safety of litifilimab for the treatment of a lifelong disorder.

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