Re-evaluation of biologic therapies in systemic lupus erythematosus

To consider the unmet therapeutic need in lupus and to review recent open-label data and clinical trials as well as to assess lessons to be drawn from these studies.

Open-label data continue to emphasize the efficacy of rituximab in refractory systemic lupus erythematosus (SLE) patients. A number of clinical trials using biologic agents, including rituximab, have not achieved their primary endpoint; however aspects of trial design such as the choice of disease activity instrument, use of concomitant medications and inadequate power to detect a realistic effect may have contributed to the endpoints not being achieved. Certain subgroups of patients within these trials also may have responded better than the whole population suggesting that SLE disease heterogeneity may be an important confounder. Recently, belimumab has been successful in two phase III trials. These trials employed a novel SLE responder index (SRI) derived from a secondary analysis of previous phase II data.

Biological therapy holds much promise in SLE and as we learn more about the disease and apply the lessons learned from recent trials, we will be in a strong position to further accelerate drug development in SLE.