Treatment with belimumab resulted in a sustained improvement of systemic lupus erythematosus (SLE or lupus) disease activity in 46% of patients at week 52, according to a novel combined responder index in results presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain.
Historically, it has been difficult to adequately measure the therapeutic responses to drug intervention in SLE patients, due to the diverse presentations of the disease itself. A novel combined responder index which takes into account three commonly used measures of disease progression -- SELENA SLEDAI (SS), physician global assessment (PGA) and presence of BILAG-classified flares (new 1A or 2B) -- was utilised by the research team to analyse the effect of the BLyS inhibitor belimumab on the progression of SLE disease activity (see note to Editors).
Lead author Dr Ellen Ginzler, of SUNY-Downstate Medical Center, New York, US, commented: "While the results demonstrated that treatment with belimumab resulted in a sustained improvement in SLE symptoms in patients with serologically active disease, we also confirmed that combining multiple disease activity measures is a successful method of assessing overall disease activity, and appears to be associated with the presence of biomarkers and quality of life improvements in responders."
Patients enrolled in this 52 week randomised, double-blind, placebo-controlled study received belimumab in doses of 1mg/kg, 4mg/kg and 10mg/kg or placebo plus SLE standard therapy. Overall, ~70% of subjects were taking prednisone and/or anti-malarials such as plaquenil ( used in SLE treatment regimes); 50% of these subjects were also taking an immunosuppressive drug (e.g., methotrexate, azathioprine, mycophenolate, leflunomide).
The 449 patients entering the study were evaluated according to the disease activity measurement scores SS and Disease Activity Index, PGA, BILAG, SF-36 and biomarkers including B-cell subsets and autoantibodies. 71.5% of the initial 449 patients entered the study with baseline serological activity. An evidence-based combined endpoint was developed that incorporates a response parameter and controls against worsening in other organ systems.
A combined response, consisting of an improvement in SS score of 4 points or more, with no new BILAG 1A or 2B flares, and no worsening in PGA (<0.3 point increase), was observed in serologically-active patients at week 52 (46% belimumab versus 29% placebo, p=0.006) and improved further to 56% for the belimumab-treated population at week 76.
Responders had a greater reduction in activated B-cells (36% responders versus 20% non-responders, p=<0.05). A greater reduction in anti-dsDNA, (antibodies created against human double stranded DNA commonly found in patients with SLE(, was also found in responders (53% responders versus 38% non-responders, p=<0.05). Responders additionally reported a greater improvement in SF-36 Physical Component Summary score (PCS; increase =4.1, MCID =2.5) at week 52 than non-responders (increase =1.0, p=<0.001).
Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that is potentially debilitating and sometimes fatal as the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage. The course of the disease is unpredictable, with periods of illness (called flares) alternating with periods of inactivity (remission). SLE is found most commonly in women.
Belimumab (LymphoStat-B) is a human monoclonal antibody that inhibits the biological activity of the B-lymphocyte stimulator (BLyS). BLyS is a naturally occurring soluble protein required for the development of B-lymphocytes into mature plasma B cells which produce antibodies. In SLE, elevated levels of BLyS are believed to contribute to the production of autoantibodies involved in damage to the body's own healthy tissues, a key marker of SLE disease activity. B-cell antagonists or inhibitors such as belimumab are believed to reduce autoantibody levels and help control SLE autoimmune disease activity.
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