GSK has announced results of the first study assessing levels of organ damage in patients with active systemic lupus erythematosus (SLE) treated with Benlysta (belimumab) plus standard of care (SoC) versus SoC alone. Patients with SLE are at risk of irreversible organ damage, which can accrue over time and is associated with increased risk of death. The data presented at the 2017 American College of Rheumatology/Association for Rheumatology Health Professionals Annual Meeting (ACR/AHRP) shows that patients treated with belimumab plus SoC had significantly less organ damage over 5 years compared to those on SoC alone.

The propensity score (PS) matched study compared patients treated with belimumab plus SoC from the BLISS-76 US long-term extension study versus patients treated with SoC alone in the Toronto Lupus Cohort (TLC), a population of SLE patients with similar clinical characteristics to those in the BLISS pivotal studies for belimumab. Propensity Score is a composite value that allows clinically similar patients to be compared.

Results demonstrated that patients treated with belimumab plus SoC had significantly less SLE-related organ damage progression (0.44 smaller unit increase in SDI score), compared to patients in the TLC receiving SoC (p=0.001). This pattern of significantly lower organ damage progression started in the first year and continued every year of the analysis (through Year 5). Patients receiving belimumab plus SoC were 61% less likely to progress to a higher SDI score over any given year of follow-up, compared to SoC patients (p<0.001). Among patients whose levels of organ damage did increase, the magnitude of year-to-year progression also reduced compared to those on SoC alone (p=0.006).

Dr. Murray Urowitz, Professor of Medicine, University of Toronto and lead author on the study said, “These findings support results from a previous analysis of the BLISS long-term extension studies, published last year. Having an appropriate SLE comparator arm has enabled us to make the first formal evaluation of long-term belimumab treatment versus standard therapy alone. The results are encouraging and indicate the potential impact of belimumab on organ damage progression in patients living with this chronic condition.”

The results of the study were validated using an alternative method of analysis, based on inverse PS weighting, which showed similar results for the change in SDI score from baseline to Year 5 for belimumab plus SoC versus SoC alone.

The safety profile observed in the BLISS-76 long-term extension study was consistent with that observed in the overall BLISS clinical trial programme for belimumab.
About the study

This was the first long-term efficacy analysis on the effect of belimumab on the rate of organ damage progression in SLE, versus SoC alone. The study compared two groups of eligible patients with similar clinical characteristics; 259 patients who had taken part in the BLISS-76 pivotal trial US long-term extension (LTE) open labelled uncontrolled study and 706 patients from an external cohort (TLC). For the primary endpoint analysis 99 patients from the LTE study and 99 patients from the TLC were 1:1 matched and the results pertain to these 198 patients.

The primary endpoint of the study was the mean change in SLICC Damage Index [SDI] score (a validated score to quantify organ damage) from baseline to Year 5 between patients treated with belimumab plus SoC versus SoC, based on data from the BLISS LTE trial and the TLC. Secondary endpoints included time to first SDI worsening between patients treated with belimumab plus SoC versus SoC alone, and total SDI score at yearly intervals between patients treated with belimumab plus SoC versus SoC alone, as well as changes in SLEDAI score and steroid use.

One of the key limitations of this study was the time period during which patients were evaluated. The TLC has collected data on its patients for decades while the belimumab trials started in 2007. Therefore, an analysis could be confounded by change in treatment patterns over time. To minimise this possibility, TLC patients with index dates before 1990 were excluded.
About Benlysta (belimumab), for injection, for intravenous and subcutaneous use only

Benlysta is currently the only medicine specifically developed and approved for SLE. Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Benlysta does not bind B cells directly. By binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

Benlysta is indicated in the US for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy: Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.

Benlysta is licensed in the European Union as an add-on therapy in adult patients with active autoantibody-positive SLE, with a high degree of disease activity (e.g. positive anti-dsDNA and low complement), despite standard therapy.  In the EU, Benlysta is licensed for injection, for intravenous use only.