SLE clinical and laboratory profiling to indentify best response to belimumab: results from the phase III belimumab clinical trials

SLE clinical and laboratory profiling to indentify best response to belimumab: results from the phase III belimumab clinical trials

Systemic lupus erythematosus (SLE) is a chronic disease affecting the immune system characterized by phase of activity and alternating periods of remission. The clinical manifestations are extremely heterogeneous with multi-systemic involvement, including symptoms such as fever and malaise, as well as dermatological, musculoskeletal, renal, respiratory, cardiovascular, hematological, and neurological manifestations. Until recently, the treatment and management of SLE were based mainly on non-steroidal anti-inflammatory drugs, glucocorticoids, hydroxychloroquine, and immunosuppressive agents. Scientific progress and the rise of biologic therapies in the treatment of SLE has resulted in a significant improvement in prognosis. Nonetheless, SLE management is still challenging because of the adverse effects of conventional therapies (especially steroids), occurrence of refractory disease and non response to treatment. As we acquire a better understanding of SLE pathogenesis, we are able to correlate clinical manifestations of SLE with specific pathogenic pathways (that is, cellular and molecular mediators that could be specifically targeted). Therefore, biological therapies could become even more important in SLE management. In the future, the management of SLE could be tailored to the patient's specific manifestations and clinical characteristics by the use of specific biological therapies.Taken the above together, these observations suggest that specific SLE populations, with specific organ involvement and pathogenic manifestations would be more likely to have a better outcome when treated with specific biological therapies, such as belimumab. All the above is in line with the risen concept of the so called precision medicine, aiming to identify sub-populations of patients with specific disease profiles who might benefit at the most of a tailored therapeutic approach. In this study, we aim to investigate the effectiveness of belimumab therapy in a post-hoc analysis on the 3 randomized controlled trials BLISS-52, BLISS-76 and BLISS-SC, when considering specific populations of SLE patient, based on their clinical and laboratory manifestations. Furthermore, we aim to investigate the role of belimumab as a steroid-sparing drug in specific patients populations. This study might demonstrate and highlight a better efficacy of belimumab when treating SLE patients with specific clinical manifestations and, potentially, suggested such an approach as first line therapy in order to maximize therapeutic effect and minimize adverse ones.

[{ "PostingID": 1416, "Title": "GSK-HGS1006-C1056", "Description": "A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 76-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects with Systemic Lupus Erythematosus (SLE)" },{ "PostingID": 1417, "Title": "GSK-HGS1006-C1057", "Description": "A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Wk Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)" },{ "PostingID": 14488, "Title": "GSK-HGS1006-C1115", "Description": "A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) Administered Subcutaneously (SC) to Subjects with Systemic Lupus Erythematosus (SLE)" }]