Sparing steroids in lupus

Abstract

Researchers at Dynavax Technologies Corp. and the Baylor Institute for Immunology Research have found that toll-like receptor antago- nists could offer a way to lower steroid dosage and thus reduce side effects in lupus patients.1 Dynavax has a toll-like receptor 7 and toll-like receptor 9 antagonist poised to enter lupus trials within the year. Lupus is a chronic autoimmune disease characterized by excess production of autoantibodies and proinflammatory cytokines that cause severe damage to multiple tissues, including the skin, joints and kidneys. There are no targeted therapies marketed for lupus. Instead, depending on disease severity, patients receive varying doses of oral or i.v. glucocorticoids in combination with hydroxychloro- quine and/or immunosuppressants such as cyclophosphamide and mycophenolate. Hydroxychloroquine is approved for malaria and for lupus, although its mechanism of action is not entirely clear in the latter. Compared with other autoimmune indications, lupus often requires high doses of glucocorticoids to reduce the frequency of flares and treat disease, putting patients at risk of a broad range of side effects including hypertension, osteoporosis, hyperglycemia, obesity and retinopathy. The Dynavax-Baylor team hypothesized that in lupus, unlike in other autoimmune diseases, the anti-inflammatory effects of glu- cocorticoids are offset by a proinflammatory pathway in immune cells, leading to the need for high-dose steroids. The group reasoned that blocking that unknown proinflammatory pathway could lead to steroid-sparing treatment regimens.