546 Gene expression signatures and ALADIN score correlates with response of alopecia areata patients to treatment with JAK inhibitors

Abstract

Alopecia areata (AA) is an autoimmune disease in which the hair follicle is the target of immune attack and manifests clinically as hair loss. The more extreme forms of the disease can result in lifelong alopecia with complete loss of scalp, face and body hair. Currently, there are no FDA-approved drugs for AA, and response to treatments are highly variable and often disappointing. Biomarkers for the purposes of precise quantitative tracking of disease severity, disease course prediction, and response to drug are valuable tools in the evaluation of novel treatments in clinical trials for AA. Previous studies by our group, including large genome-wide association studies and meta-analyses, gene expression analyses conducted on human AA scalp skin biopsies and animal models, and targeted cytokine antibody treatments in the murine form of AA, provided a strong rationale for targeting Janus kinase signaling intermediates for the purposes of treatment. Our center recently completed two pilot, open-label clinical trials of the JAK inhibitors ruxolitinib and tofacitinib, for the treatment of AA. Using previously collected whole genome gene expression data collected from a large cohort of patients with AA as well as normal controls, a multifactorial metric we termed the Alopecia Areata Disease Activity Index, or ALADIN, was created. In this study, we used the ALADIN metric to measure responses of AA patients enrolled in our clinical trials of JAK inhibitors. This tool tracked with clinical score and demonstrated strong correlation with response to treatment. Furthermore, ALADIN component genes, which include GZMA, PRF1, CXCL9, CXCL10 as well as hair-keratin associated genes, differentiated eventual responders from nonresponders at baseline in some cases. ALADIN is a powerful biomarker tool that will be useful in clinical trials of novel treatments for AA, particularly in larger randomized clinical trials.