Other strategies for B cell interventions target B cell surface receptors, soluble modulators that lead to B cell proliferation and differentiation, and B cell signaling mechanisms downstream of the B cell receptor, Dr. Dall’Era noted. Drugs recently under investigation for BAFF-blockade include blisibimod, tabalumab and atacicept, which is unique in that it targets both BAFF and APRIL (a proliferation-inducing ligand).
Evidence for the role of type 1 interferons in SLE includes the fact that treatment with interferon-alpha leads to a lupus-like disease, risk polymorphisms for lupus are present in interferon-regulated genes, interferon signature is present in peripheral blood mononuclear cells and in tissues from lupus patients, and the level of expression of interferon-inducible genes correlates with disease activity. Drugs that have been studied include rontalizumab and sifalimumab, whose development have been discontinued; and anifrolumab, which is continuing in Phase III trials.
More than 500 current clinical trials of lupus therapies point toward a bright future, increasing the likelihood of demonstrating efficacy of novel experimental agents. —Dr. Dall’Era
Advances in Treating Lupus Nephritis
A major manifestation of SLE, lupus nephritis, is also being targeted with new treatment strategies, Dr. Dall’Era reported. Conventional induction treatment involves high doses of glucocorticoids, along with such drugs as mycophenolate mofetil or cyclophosphamide. An emerging strategy is multi-target therapy, she said, “already standard of care in the treatment of patients who have undergone organ transplant.” One recent small trial demonstrated the efficacy of the combination of tacrolimus and mycophenolate mofetil when compared with intravenous cyclophosphamide for induction treatment of lupus nephritis. Another trial in progress is studying the combination of voclosporin (a next generation calcineurin inhibitor) in combination with mycophenolate mofetil.
Another active area of research involves novel ways to use rituximab for the treatment of lupus nephritis. The Rituxilup trial, with European and American collaborators, is assessing the use of rituximab instead of, rather than as add-on therapy to, oral steroids. Rituximab is being given in combination with two doses of intravenous steroids and followed by mycophenolate mofetil. In the CALIBRATE trial, patients with lupus nephritis are undergoing an induction regimen of rituximab and two doses of intravenous cyclophosphamide, followed by belimumab maintenance.
Larry Beresford is an Oakland, Calif.-based freelance medical journalist.
References
- Van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: High disease activity predictors of response. Ann Rheum Dis. 2012 Aug;71(8):1343–1349.
