DR. CORA LIM-MEDICAL INSIDER
Systemic Lupus Erythematosus
PART 8
This is now Part 8 of our discussion of Systemic Lupus Erythematosus (SLE).
Biologic therapies
According to studies, the development of biologic therapies in SLE has lagged behind other rheumatological conditions, such as rheumatoid arthritis.
However, the same research shows that an increased understanding of the molecular and cellular biology of SLE has led to targeted therapies now becoming available for use.
Belimumab is the first drug to be licensed by the US Food and Drug Administration for SLE in 60 years. Belimumab is a humanised monoclonal antibody that inhibits the cytokines B-lymphocyte stimulator or B-cell activating factor (BLyS/BAFF) and a proliferation-inducing ligand (APRIL) thus, targeting B-cells. In two large phase III clinical trials, BLISS 52 and BLISS 72, belimumab demonstrated efficacy in patients with mild to moderate manifestations of SLE, namely musculoskeletal and mucocutaneous disease.
Despite a number of negative clinical trials of novel biologic therapies in SLE, a number of ongoing studies are showing promising results, including monoclonal antibodies against type-1 interferons such as sifalimumab. In the UK, initial rejection of belimumab by the National Institute for Health and Care Excellence was appealed and it is now approved as an additional therapy in patients with active autoantibody-positive SLE. Patients must demonstrate ongoing serological evidence of active disease with a positive dsDNA antibody level, low complement and a high disease activity score on the Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) despite treatment. Treatment with belimumab can only be continued beyond 24 weeks if the SELENA-SLEDAI score improves by four or more points.
Rituximab is a chimeric mouse/human monoclonal antibody to CD20, a B-cell surface antigen. CD20 is a transemembrane cellular phosphoprotein that is expressed by around 95% of the B-cell population, but not by plasma cells.
Rituximab was developed for use in B-cell malignancies and causes selective B-cell depletion.
While a large evidence base exists supporting the use of rituximab in SLE, disappointingly, two large clinical trials in lupus nephritis (LUNAR) and non-renal SLE (EXPLORER) failed to meet their primary endpoints.
Despite this, there is widespread use of rituximab – particularly in those with resistant disease. There are several case series of good response that support the use of rituximab. Further randomised controlled trials of rituximab in SLE are currently underway. In the UK, the use of rituximab in patients with SLE is permitted by NHS England provided data on patient outcomes are captured in the BILAG biologics registry.