Cytokine-targeted treatment in alopecia areata - new possibilities?

Abstract

Alopecia areata is a form of non-scarring hair loss characterised by a recurrent and difficult-to-treat course. The aetiology of this disease is still incompletely understood. However, multiple immunological pathways and an abnormal cytokine profile in patients with alopecia areata have been described. There are many therapeutic options for patients with alopecia areata, including topical, intralesional or systemic corticosteroids, contact immunotherapy, phototherapy and non-corticosteroid immunosuppressive drugs such as cyclosporine, methotrexate or azathioprine. However, these treatments have limited efficacy and may be associated with side effects. In addition, Janus kinase inhibitors have been shown to cause metabolic disorders. Therefore, their use in patients with alopecia areata may be limited. Other cytokine-targeted therapies have been shown to be effective in alopecia areata, such as apremilast (a phosphodiesterase 4 inhibitor), ustekinumab (a human immunoglobulin (Ig) G1 kappa monoclonal antibody directed against interleukin 12 and 23), abatacept (a soluble fusion protein which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 to the modified Fc portion of human immunoglobulin G1), secukinumab (an IL-17A antagonist) and dupilumab (a monoclonal antibody that blocks interleukin 4 and interleukin 13). TNF inhibitors (such as infliximab, adalimumab and etanercept) have been described to be ineffective in alopecia areata. In addition, disease exacerbation after TNF therapy has been reported. Alefacept (an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding part of human leukocyte function antigen-3 fused to the Fc part of human IgG1) and efalizumab (anti-CD11a monoclonal antibody) have not shown efficacy in alopecia areata. There are also isolated reports of alopecia areata after therapy with omalizumab (recombinant humanised monoclonal antibody anti-IgE), ixekizumab (inhibitor of IL-17A) and brodalumab (inhibitor of IL-17R).