Pamela M. Lutalo

Novel therapeutic agents in clinical development for systemic lupus erythematosus

Conventional immunosuppressive therapies have radically transformed patient survivalin systemic lupus erythematosus (SLE), but their use is associated with considerabletoxicity and a substantial proportion of patients remain refractory to treatment. Amore comprehensive understanding of the complexity of SLE immunopathogenesis hasevolved over the past decade and has led to the testing of several biologic agents inclinical trials. There is a clear need for new therapeutic agents that overcome theseissues, and biologic agents offer exciting prospects as future SLE therapies.An array of promising new therapies are currently emerging or are under developmentincluding B-cell depletion therapies, agents targeting B-cell survival factors,blockade of T-cell co-stimulation and anti-cytokine therapies, such as monoclonalantibodies against interleukin-6 and interferon-α.

Update on belimumab for the management of systemic lupus erythematosus

Introduction: Belimumab is a fully humanised mAb against B lymphocyte stimulator (B-LyS). It is the first biological drug to be licensed and approved by the US FDA and the European Medicines Evaluation Agency for use in combination with standard immunosuppressants in autoantibody-positive systemic lupus erythematosus (SLE). The clinical effectiveness and impact of this drug on lupus morbidity and mortality is evaluated in this review. Areas covered: An overview of the efficacy and safety of belimumab based on 7-year longitudinal continuation study data from SLE patients enrolled in the Phase II double-blind, randomised, placebo-controlled, 52-week study of belimumab 1, 4 and 10 mg/kg doses and an overview of the open-label 24-week extension of belimumab plus standard immunosuppressant therapy. A review of the current belimumab clinical trials, the experience of belimumab in real-world settings and a description of the impact that belimumab has had on the healthcare quality of life of SLE patients. Expert opinion: The emerging clinical data have shed light on the areas in which belimumab is of greatest benefit and areas for further evaluation in clinical trials. It is anticipated that regular updates from ongoing trials of belimumab in SLE, practising physicians, data from the continuation arms of clinical trials and data from international biologics registries will have an influence on the role of belimumab in the management of SLE.

Progress with the use of monoclonal antibodies for the treatment of systemic lupus erythematosus.

In recent years, significant progress has been made in the use of monoclonal antibodies in the treatment of systemic lupus erythematosus (SLE). Advances in our understanding of the complexity of SLE immunopathogenesis have led to the testing of several biologic agents in clinical trials. Monoclonal therapies currently emerging or under development include B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and anticytokine therapies. Issues remain, however, regarding clinical trial design and outcome measures in SLE which need to be addressed to optimize translation of these promising therapies into clinical practice.

Which dose of steroids and which cytotoxics for severe lupus

There have been a number of major advances in the treatment of systemic lupus erythematosus and we are now in the era of biologic therapies for this multisystem autoimmune disorder. There has been a greater awareness of the toxicities of the traditional therapies including the recognition that the doses of corticosteroids used in the past have been excessive, resulting in unacceptable toxicities. Other advances have included the development of lower cumulative doses of cyclophosphamide and the widespread acceptance of mycophenolate mofetil for the treatment of lupus nephritis. This review addresses the current management of severe lupus with corticosteroids and cytotoxic agents.