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Silverman talks new treatments, pathogenesis of SLE
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NEW YORK CITY— The elimination of B cells may be the key to controlling disease activity for patients with systemic lupus erythematosus, although the disease is heterogeneous, according to a speaker here.
Gregg J. Silverman, MD, discussed new treatment opportunities and the pathogenesis of systemic lupus erythematosus (SLE) at the Interdisciplinary Autoimmune Summit. He said many current treatments used by physicians are off-label use based on what is approved for SLE by the FDA, namely aspirin, hydroxychloroquine, corticosteroids, and more recently, belimumab (Benlysta, GlaxoSmithKline).
Other agents that have been studied have failed, according to Silverman. Rituximab (Rituxan, Genetech), epratuzumab (Embody, UCB) and atatacept (Orencia, Bristol-Myers Squibb) have failed to meet primary endpoints in clinical trials for patients with SLE, he said, but some of the agents have continued to be tested in combination with other drugs, like cyclophosphamide. However, he said belimumab is “postulated to restore balance in the immune system, in part by acting on autoantibody-producing B cells to undergo normal process of cell death.”
Silverman said new treatment pathways are currently being explored and have demonstrated efficacy in an open-label extension study. A Fc-gamma receptor, SM101 (SuppreMol, GmbH), part of the immunoglobulin G expression pathway, is being explored for lupus nephritis in a phase 2 clinical trial. Silverman also said PF-04236921 (Pfizer), an interleukin-6 inhibitor, is in a phase 2b randomized clinical trial for patients with SLE. He said a study of eight patients with refractory SLE demonstrated promising results from off-label treatment with bortezomib (Velcade, Millennium Pharmaceuticals), a proteasome inhibitor approved for multiple myeloma. Other drugs, including sifalimumab and anifrolumab (AstraZeneca and MedImmune), are also in phase 2 trials and target interferon. – by Shirley Pulawski
Reference:
Silverman GJ. SLE treatments: New opportunities. Presented at: Interdisciplinary Autoimmune Summit. April 1-3, 2016; New York City.
Disclosure: Silverman reports he is a consultant for Roche, Lilly, Pfizer, Onyx and Quest and receives grant support from the NIH, Lupus Research Institute and the American College of Rheumatology Research Foundation.