Patients with systemic lupus erythematosus ( SLE ) are at risk of irreversible damage across multiple organ systems because of both active disease and medication toxicities.
The severity and frequency of damage increases over time, and patients with damage have consistently been shown to be at risk of accruing additional damage. If left untreated, this can lead to serious and even fatal complications, particularly in patients with vital organ involvement such as heart, kidney, lungs or central nervous systems.
As the only approved biological treatment for SLE, Belimumab ( Benlysta ) has demonstrated a clinically meaningful reduction in SLE disease activity in the phase III BLISS pivotal trials.
Assessing the level of organ damage in patients receiving Belimumab expands the understanding of its benefits when used long-term.
Both analyses, which used data from the long-term extension studies from the pivotal BLISS studies, showed low rates of organ damage with Belimumab treatment.
The data in patients receiving Belimumab have also provided further evidence of the importance of B-lymphocyte stimulator ( BLyS, an important factor in the survival of B cells ) in the development of symptoms of SLE, including longer-term organ damage.
The long-term organ damage analysis ( Van Vollenhoven RF et al ) reports data from the long-term single-arm extension study in 735 non-US patients treated with Belimumab for up to 9 years.
For the efficacy endpoint ( change in SLICC Damage Index [ SDI ] from baseline, a validated score to quantify organ damage, at study year 8 ), 87.7% patients treated with Belimumab had no increase in organ damage.
The incidence of adverse events ( including infections, malignancies, depression, suicide, self-injury and death ) remained stable or declined over time.
The propensity score ( PS ) matched analysis ( Urowitz M et al ) has reported the comparison of pooled data from the BLISS long-term extension studies with data from the Toronto Lupus Cohort ( TLC ) over 5 years.
The PS is a composite value that allows clinically similar patients to be compared.
Patients treated with Belimumab plus standard of care ( SoC ) had significantly less progression of SLE-related organ damage ( 0.45 smaller unit increase in SDI score ), compared with patients in the TLC receiving SoC ( N=181, p less than 0.001 ).
Patients treated with Belimumab plus SoC were 60% less likely to progress to a worse SDI score over any given year of follow‑up compared with SoC patients ( N=323, p less than 0.001 ).
A patient receiving Belimumab plus SoC has a 3.1% annual probability of organ damage progression compared with a 7.5% annual probability with SoC ( N=323 ).
The long-term safety observed in both analyses was consistent with the known safety profile of Belimumab.
Belimumab, currently the only medicine specifically developed and approved for SLE, is a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS.
Belimumab does not bind B cells directly. By binding BLyS, Belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.
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.
Systemic lupus erythematosus is the most common form of lupus, affecting approximately 70% of an estimated 5 million people with lupus worldwide.
SLE is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time including painful or swollen joints, extreme fatigue, unexplained fever, skin rashes and organ damage. ( Xagena )
Source: GSK, 2018