Extract

Anifrolumab efficacy in cutaneous lupus erythematosus parallels changes in blood transcriptomic and cellular biomarkers

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Treatment of cutaneous lupus erythematosus (CLE) remains a therapeutic challenge. In contrast to systemic lupus erythematosus (SLE), B-cell-depleting therapy such as rituximab and belimumab has limited efficacy in CLE. Targeting type I interferon (IFN) has proved successful in SLE, so could this be a therapeutic option for CLE? The present study examines the clinical and mechanistic effects of anifrolumab, a type I IFN receptor blocker, in five patients with discoid lupus erythematosus (DLE), one patient with chilblain lupus erythematosus and one with subacute CLE. All patients were refractory to standard therapy, the median number of prior therapies being six, with resistance to rituximab confirmed in six of the seven patients. With monthly intravenous anifrolumab 300 mg infusions, median CLE Disease Area and Severity Index (CLASI) score decreased from 17 at baseline to 6 at 1 month and 0 by 3 months. One patient discontinued treatment due to severe herpes zoster. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy, while other cell subsets showed no substantive changes on flow cytometry. The same was true of the blood transcriptomic signature, with only discrete subsets of the SLE blood IFN signature being suppressed. These data suggest the potential efficacy of anifrolumab in DLE and rituximab-resistant CLE, without suppression of all IFN-stimulated genes or the wider SLE blood transcriptome.

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