Until recently, no agents had received U.S. Food & Drug Administration (FDA) approval for the treatment of lupus nephritis. Thus, therapy has varied widely, although results reported in clinical trials have influenced the choice of agents in selected populations.
The paper by Haj-Ali et al. provides a retrospective picture of the treatment of lupus nephritis in an ethnically diverse population at an academic center experienced in the management of lupus. Although the number of patients in this study is limited, the data suggest that the responses to treatment with MMF and cyclophosphamide (CYC) at 104 weeks are better than responses to treatment with either MMF with tacrolimus, or rituximab with CYC.
The results of the study differed from those of previous studies with respect to outcomes in African American and Hispanic patients; these differences may relate to the use of MMF as a first-line therapy and the use of low-dose CYC and rituximab as rescue options.
Data from real-world experiences are valuable adjuncts to randomized clinical trials, despite the many uncertainties. Indeed, studies of this kind will provide necessary comparative data as new agents (i.e., belimumab and voclosporin) become part of the armamentarium of drugs used to treat one of the most serious manifestations of SLE.
Abstract 1744—Improvement of renal and non-renal SLE outcome measures on sirolimus therapy—a 21-year follow-up study of 73 patients7
Research by Piranavan P, Perl A
Until the recent approval of drugs with a specific indication for lupus nephritis, treatment of this serious complication involved a wide range of immunosuppressive agents essentially borrowed from other fields. Cyclophosphamide, azathioprine and mycophenolate mofetil (MMF) achieved the greatest use, with rituximab also used, depending on the clinical setting. Sirolimus has represented another alternative given its extensive use in the setting of organ transplantation.
Sirolimus inhibits the mechanistic target of rapamycin (mTOR), a serine-threonine kinase, that may be important in driving immune dysfunction in SLE. As the study of Piranavan et al. shows, sirolimus is well tolerated by patients and is effective in reducing serological, as well as clinical, manifestations of SLE, both renal and non-renal.
As the number of approved agents for SLE increases, studies will be needed to determine the best pharmacologic approaches for the various manifestations of lupus and the role of sirolimus among the other agents, especially for severe disease complications, such as nephritis.
Abstract 1423—Ability of soluble immune mediators and SLE-associated autoantibody specificities to forecast transition to classified SLE and inform a lupus classification risk immune index8