Question

Explain the immunotherapeutic approaches for Systemic Lupus Erythomatosus.

Answer 1

There have been significant advances in the treatment of SLE, which have produced major impacts on morbidity and in some cases mortality. The major drugs of the last three decades in treatment of SLE have been corticosteroids, AZA, MTX and cyclophosphamide. However, these drugs have considerable toxicities, and with the increasing knowledge of the immune system, and further understanding of SLE immunopathogenesis, many groups are seeking to identify and trial novel immunotherapeutic strategies. These have included therapies aimed at influencing particular immune cells (e.g. B cells) and molecules (e.g. costimulatory molecules, cytokines) which are thought to be important in disease pathogenesis. The advantage of such therapies is that efficacy may be achieved with lower toxicity, and without wide-ranging suppression of the immune system. Success has not always been achieved by specific design of immunotherapies for SLE, and the best recent example has been the use of B-cell depletion therapy, a concept derived from its successful use in RA. In this article, we discuss those immunotherapeutic strategies that have arrived as far as clinical trials in human subjects. In addition to these relatively specific immunotherapies, we also highlight the use of mycophenolate mofetil, an anti-proliferative immunosuppressant which has had good success over the last 10 yrs, with similar early efficacy to cyclophosphamide when used as induction therapy for lupus nephritis. Data are presented on more generalized immune strategies, such as the use of stem cell transplantation and intravenous immunoglobulin.There have been significant advances in the treatment of SLE, which have produced major impacts on morbidity and in some cases mortality. The major drugs of the last three decades in treatment of SLE have been corticosteroids, AZA, MTX and cyclophosphamide. However, these drugs have considerable toxicities, and with the increasing knowledge of the immune system, and further understanding of SLE immunopathogenesis, many groups are seeking to identify and trial novel immunotherapeutic strategies. These have included therapies aimed at influencing particular immune cells (e.g. B cells) and molecules (e.g. costimulatory molecules, cytokines) which are thought to be important in disease pathogenesis. The advantage of such therapies is that efficacy may be achieved with lower toxicity, and without wide-ranging suppression of the immune system. Success has not always been achieved by specific design of immunotherapies for SLE, and the best recent example has been the use of B-cell depletion therapy, a concept derived from its successful use in RA. In this article, we discuss those immunotherapeutic strategies that have arrived as far as clinical trials in human subjects. In addition to these relatively specific immunotherapies, we also highlight the use of mycophenolate mofetil, an anti-proliferative immunosuppressant which has had good success over the last 10 yrs, with similar early efficacy to cyclophosphamide when used as induction therapy for lupus nephritis. Data are presented on more generalized immune strategies, such as the use of stem cell transplantation and intravenous immunoglobulin.