Table 4

Potential new targeted therapies for SLE

DrugTargetRationaleTrial data available
IL, interleukin.
LJP 394B cellsInhibit production of anti-dsDNA antibodies. Cross links anti-dsDNA antibodies leading to anergy and deletion of B cells rather than activation, as drug does not carry T cell epitope and cannot recruit T cell helpTo date no evidence of reduced rate of renal flare. Phase II clinical studies to identify precise potential role continue
Anti-CD20 antibodyB cellsInhibits production of anti-dsDNA antibodies. CD20 expressed on all activated B-cells and when recognised by anti-CD20 antibody causes lysis of these cells. Currently licensed for non-Hodgkins lymphomaRecent small study has demonstrated saftey and some efficacv at higher doses. Currently underway at our centre is an open labelled study. Thus far 7 patients treated with encouraging results. Data from larger controlled studies required
Anti-IL-10 antibodiesIL-10IL-10 consistently raised in SLESmall study of 6 patients treated showing improvement in skin and joint manifestations
Anti-CD40 ligand (L)CD40 LC40L expressed on T cells provides an important co-stimulus to T cell activation. This interaction also has significant effects on B cells, for example, augmenting B cell responses to cytokines and causing antibody isotype switchingOne study found this to be tolerated well. However a recent study was discontinued due to concerns regarding major vascular events, namely myocardial infarction and stroke
LeflunomideT and B cellsInhibits pyrimidine synthesis thus blocking RNA and DNA synthesis in T and B cells and hence inhibits proliferation of these cells. Currently licensed for rheumatoid arthritisFirst short term studies have shown it to be safe and reasonably effective