Safety and Efficacy of Combination Belimumab and Voclosporin in the Treatment of Proliferative Forms of Lupus Glomerulopathy: Synergy Trial

Description

Lupus nephritis (LN) is the most serious common manifestation of systemic lupus erythematosus (SLE) and will ultimately affect about half of patients with SLE. LN increases the morbidity and mortality of patients with SLE, especially if Chronic Kidney Disease (CKD) and end-stage kidney disease (ESKD) develop. Morbidity and mortality are significantly mitigated if treatment-induced complete remission (CR) is achieved. While partial remission (PR) is better than no remission, its impact on renal survival is much less than CR. Within the last two years VCS and BEL have been approved for the treatment of LN, bescause each drug was shown to increase the number of patients having CR in well-conducted phase III trials. However, the overall proportion of patients achieving CR was below 50% in each trial, leaving a large unmet need for most patients with LN. Because VCS and BEL target different effector arms of the immune system relevant to kidney injury in LN, and individually have excellent safety profiles, investigators postulated that for the treatment of LN the combination of VCS and BEL with a significant reduction in mycophenolate-based immunosuppression may be complementary and safe, and would ultimately increase the proportion of patients who achieve a CR. In addition, both drugs offer different kidney-protective effects that favor long-term preservation of kidney function. Specifically, VCS protects podocytes and BEL reduces the LN flare rate and through unknown mechanisms, attenuates the decline in GFR seen in LN patients. Investigators further postulate that the combination of these targeted treatments will significantly reduce the need for non-specific immunosuppressives (cytotoxic agents and antimetabolites).