Anifrolumab for treatment of refractory cutaneous lupus erythematosus

Abstract

Cutaneous lupus erythematosus (CLE) is a spectrum of skin changes related to systemic lupus erythematosus (SLE), a family of autoimmunity manifesting characteristic multisystem inflammation and damage. Treatment of CLE continues to evolve, especially for patients with moderate to severe disease. Type 1 interferon (IFN-1) plays a significant role in CLE pathogenesis. Anifrolumab, a fully humanized monoclonal antibody, selectively binds and inhibits the IFN-a receptor 1. Evidence from multiple Phase II and III randomized trials resulted in approval for anifrolumab for treatment of moderate to severe SLE. We present a case series of three patients with refractory CLE significantly improved with anifrolumab. The patients were recruited via clinic interaction and treated with anifrolumab from January 2021 to April 2022. Each patient received at least 12 weeks of therapy. Treatment and follow-up is ongoing. Patients were eligible for the study if they were a patient of the UNC Hospital System with resistant CLE, defined as having received inadequate disease control with standard therapies, including antimalarials, disease-modifying agents and biologics. Outcome measures were improvement in patient-reported symptoms and physician observation of erythema and pigmentary changes. All cases demonstrated significant improvement in disease appearance, cutaneous involvement, and symptomology after treatment with 2 months of anifrolumab infusions. Anifrolumab shows great potential for improving CLE in patients who have failed standard of care and multiple treatment options, including those that have failed belimumab or those who smoke. This report highlights the value of anifrolumab in managing patients with refractory CLE.

Assessment of Clinical Response to Anifrolumab in Patients With Refractory Discoid Lupus Erythematosus

“…Importantly, in its hallmark phase 3 trial TULIP-2, anifrolumab not only met its primary end point via reduction in SLE activity, but it also demonstrated benefit in lupus-associated skin disease, with 49% of patients in the anifrolumab group having a 50% or more reduction in CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) activity score vs 25% in the placebo group. A subsequent case series of 3 patients with refractory CLE treated with anifrolumab reported improvements in physician observation of erythema and pigmentary changes, although a validated outcome measure of cutaneous lupus activity was not used. Although specific CLE subtypes were not characterized in these previous reports, given that type 1 interferon expression is known to correlate with DLE disease activity, we hypothesized that anifrolumab might be a viable therapeutic option for patients with DLE.…”

Steroid-free flare management of a severe cutaneous lupus flare with anifrolumab

“…There are a few reports and case series demonstrating efficacy of ANI in refractory skin disease; 7,11 however, to our knowledge, this is the first report of the management of a severe refractory cutaneous lupus erythematosus flare with ANI without increasing the GC dose. We suggest that due to the rapid onset of action, ANI might be a feasible option for flare management without an increased use of GC and, importantly, may reduce the long-term impact associated with high-dose GC therapy.…”

Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

“…In light of these interesting results in SLE patients, first reports regarding the use of anifrolumab in CLE patients are available. Only recently, successful use in a case series of three patients was published by an American group [ 164 ]. Interestingly, the patients reported were pretreated heavily with second- and third-line treatments, even belimumab.…”