Why targeted therapies are necessary for systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective.

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus

“…Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune disease (AD) characterized by a wide range of clinical and serological manifestations and a high disease burden [ 1 ]. SLE pathophysiology encompasses several mechanisms, such as T cell and B-cell abnormalities, impaired apoptotic debris clearance, autoantibody production, and abnormal cytokine secretion [ 2 ].…”

New Perspectives in Rheumatology: May You Live in Interesting Times: Challenges and Opportunities in Lupus Research

“…First, conventional clinical trials have significant drawbacks, including short duration, efficacy of background therapy, outcome measurements, and the magnitude of the placebo effect, among others. These topics have been extensively discussed elsewhere and will not be further considered here. Second, SLE is a highly heterogeneous disease in which separate clinical manifestations and, accordingly, therapeutic responses may be mediated by distinct mechanisms.…”

Inducible nitric oxide synthase and systemic lupus erythematosus: a systematic review and meta-analysis

“…Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by a variety of clinical symptoms, producing autoantibodies and causing damage to multiple organs [1][2][3]. However, the pathogenesis of SLE remains unclear.…”