INTRODUCTION
The type 1 interferon (IFN) signaling pathway is considered a key player in the pathogenesis of systemic lupus erythematosus.1,2 Elevated serum levels of type 1 IFNs and IFN-inducible gene expression in the peripheral blood of patients with SLE are associated with disease severity, activity, and clinical manifestations.3-5 Type 1 IFNs are cytokines with myriad effects, including antiviral, antiproliferative, antitumor, and immunomodulatory activities1; autoimmune diseases such as SLE may be a result of chronic or dysfunctional activation of this pathway precipitated by self-nucleic acids in autoimmune complexes.6 Targeting this pathway for the treatment of SLE is of interest; anifrolumab, a type 1 IFN-receptor antibody, is now approved for the treatment of SLE and emerging research suggests particular benefit for refractory cutaneous lupus erythematosus (CLE).7-9 Dermatologists should be familiar with the mechanism of anifrolumab and its efficacy in treating SLE/CLE and other dermatologic diseases.
Mechanism of Action
Anifrolumab is a humanized immunoglobulin (IgG)1k monoclonal antibody to the type 1 IFN-alpha receptor subunit 1 (IFNAR1), blocking the action of all type 1 IFNs and inducing internalization of IFNAR1. Through inhibition of receptor-mediated type 1 IFN signaling, anifrolumab disrupts IFN-responsive gene expression and the downstream, dysfunctional inflammatory and immunological cascades that lead to tissue damage associated with disease activity.10
Indications, Efficacy, and Safety
Systemic Lupus Erythematosus
Anifrolumab is FDA-approved for the treatment of patients with moderate to severe SLE on standard therapy.10 Three randomized, double-blind, and placebo-controlled clinical trials -- two phase III studies (TULIP-1 and TUILP-2) and one phase IIb study (MUSE) -- established intravenous anifrolumab 300 mg administered every 4 weeks as efficacious across multiple clinical disease severity assessments. Notably, anifrolumab led to a sustained reduction in oral corticosteroid dosage, reduced number of flares, and improvement in the cutaneous lupus erythematous disease area and severity index (CLASI).10-13 Anifrolumab was found to be safe and tolerable across all three trials; common adverse effects included upper respiratory tract infections, infusion-related reactions, and nasopharyngitis, and an increased incidence of herpes zoster was observed in the treatment arm.10
Cutaneous Lupus Erythematosus Subtypes
Although subtypes of CLE were not specifically characterized in the three major clinical trials, several case reports and series have found anifrolumab to effectively treat several subtypes, including discoid lupus erythematosus (DLE),14-16 lupus erythematosus panniculitis,17 and subacute CLE (SCLE),18 among others. Additionally, a case report described the successful use of anifrolumab in treating Rowell syndrome (erythema multiforme-like lesions in the setting of SLE or CLE) with severe mucosal involvement after failing therapy escalation with multiple first-line treatments and belimumab.19 Notably, anifrolumab is found to be rapidly effective even in refractory disease (Figure 1A and 1B).20,21 For example, a case series describing 11 patients with SLE and one or more CLE subtypes (CLE, SCLE, chilblains lupus) treated with anifrolumab 300 mg intravenously every 4 weeks were all found to experience a decrease of CLASI activity of at least 50% at week 16, with a median time of 4 weeks to reach this point.20 Furthermore, sustained improvement in CLASI activity was observed for all patients and 54% (6/11) experienced a complete response.20
Although subtypes of CLE were not specifically characterized in the three major clinical trials, several case reports and series have found anifrolumab to effectively treat several subtypes, including discoid lupus erythematosus (DLE),14-16 lupus erythematosus panniculitis,17 and subacute CLE (SCLE),18 among others. Additionally, a case report described the successful use of anifrolumab in treating Rowell syndrome (erythema multiforme-like lesions in the setting of SLE or CLE) with severe mucosal involvement after failing therapy escalation with multiple first-line treatments and belimumab.19 Notably, anifrolumab is found to be rapidly effective even in refractory disease (Figure 1A and 1B).20,21 For example, a case series describing 11 patients with SLE and one or more CLE subtypes (CLE, SCLE, chilblains lupus) treated with anifrolumab 300 mg intravenously every 4 weeks were all found to experience a decrease of CLASI activity of at least 50% at week 16, with a median time of 4 weeks to reach this point.20 Furthermore, sustained improvement in CLASI activity was observed for all patients and 54% (6/11) experienced a complete response.20
