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.
ImportanceHidradenitis suppurativa (HS) is a common and severely morbid chronic inflammatory skin disease that is reported to be highly heritable. However, the genetic understanding of HS is insufficient, and limited genome-wide association studies (GWASs) have been performed for HS, which have not identified significant risk loci.ObjectiveTo identify genetic variants associated with HS and to shed light on the underlying genes and genetic mechanisms.Design, Setting, and ParticipantsThis genetic association study recruited 753 patients with HS in the HS Program for Research and Care Excellence (HS ProCARE) at the University of North Carolina Department of Dermatology from August 2018 to July 2021. A GWAS was performed for 720 patients (after quality control) with controls from the Add Health study and then meta-analyzed with 2 large biobanks, UK Biobank (247 cases) and FinnGen (673 cases). Variants at 3 loci were tested for replication in the BioVU biobank (290 cases). Data analysis was performed from September 2021 to December 2022.Main Outcomes and MeasuresMain outcome measures are loci identified, with association of P < 1 × 10−8 considered significant.ResultsA total of 753 patients were recruited, with 720 included in the analysis. Mean (SD) age at symptom onset was 20.3 (10.57) years and at enrollment was 35.3 (13.52) years; 360 (50.0%) patients were Black, and 575 (79.7%) were female. In a meta-analysis of the 4 studies, 2 HS-associated loci were identified and replicated, with lead variants rs10512572 (P = 2.3 × 10−11) and rs17090189 (P = 2.1 × 10−8) near the SOX9 and KLF5 genes, respectively. Variants at these loci are located in enhancer regulatory elements detected in skin tissue.Conclusions and RelevanceIn this genetic association study, common variants associated with HS located near the SOX9 and KLF5 genes were associated with risk of HS. These or other nearby genes may be associated with genetic risk of disease and the development of clinical features, such as cysts, comedones, and inflammatory tunnels, that are unique to HS. New insights into disease pathogenesis related to these genes may help predict disease progression and novel treatment approaches in the future.
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