Belimumab (Benlysta) is a human monoclonal antibody that inhibits B-lymphocyte stimulator that is approved by the US Food and Drug Administration for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy. At the 2013 annual meeting of the American College of Rheumatology held in San Diego, California from October 25-30, 2 presentations demonstrated evidence for the benefit of belimumab in patients with SLE.
Reddy and colleagues (Abstract 1574) presented data on the demographics, the duration and clinical manifestations of SLE, and the clinical response to belimumab of 166 patients with SLE from 9 academic clinical practices. The patient demographics included a mean age of 42.9 years, 92.8% female, 69.0% white, 22.5% black, and an average SLE disease duration of 12.7 years. Concomitant medications use in these patients were antimalarials; immunosuppressants, including azathioprine, mycophenolate mofetil, or methotrexate; and prednisone (71%). The predominant clinical manifestations in these patients driving treatment were arthritis, rash, serositis, lupus nephritis, hematologic abnormalities, and/or the inability to taper steroids. Of the 130 patients who had been receiving belimumab for at least 3 months, 64 (49%) had clinically responded within that time, with marked improvements in arthritis and/or rash.
Of the 92 patients who had been receiving belimumab for at least 6 months, 52 (56%) had clinically responded with improvements in arthritis, rash, and/or lupus nephritis. In the 24 African-American patients using belimumab for at least 3 months, 67% showed responses with improvements in arthritis and/or rash. In the 21 African-American patients usingbelimumab for at least 6 months, 81% responded with improvements in arthritis, rash, and/or nephritis.
These data provide evidence that the efficacy observed with belimumab in phase 3 clinical trials is duplicated in clinical practice within 3 months, and they support the use of belimumab across all ethnic groups.
In phase 3 studies, treatment with belimumab in autoantibody-positive patients with SLE for up to 76 weeks resulted in a sustained reduction in naïve and activated B-cell subsets, as well as in serum immunoglobulin (Ig)G levels. Struemper and colleagues (Abstract 1603) presented an analysis of long-term changes in B-cell subsets and in IgG levels beyond 76 weeks through 172 weeks of continued treatment with belimumab. B-cell, B-cell subset, and IgG data were collected in the phase 3 BLISS-76 study and in its US extension. Patients with SLE who were randomized to belimumab 1 mg/kg or to belimumab 10 mg/kg received biweekly doses of belimumab for the first month, followed by dosing every 4 weeks thereafter, starting at week 76. The patients in both groups continued to receive standard of care SLE agents (ie, corticosteroids, immunosuppressants, and/or antimalarials).
The results showed a continued decline of B-cell subsets beyond 76 weeks of treatment; after 172 weeks of continued belimumab dosing, an 80% to 90% net reduction for naïve, activated, and plasmacytoid B-cells, a 70% to 75% reduction for CD19+/CD20+ B-cells, and a 50% to 60% reduction for plasma cells were reported. Memory B-cells showed a biphasic response to belimumab, with a rapid rise through week 8, followed by a slow decline, possibly as a result of transient redistribution of these cells from lymphoid tissues to the circulation. During the 172 weeks, IgG levels were reduced by 20% to 30%, but this was not associated with the development of severe infections. The results for the 1-mg/kg and 10-mg/kg groups were similar for most measures in the timing and magnitude of the responses. These data show that treating patients with SLE with belimumab for 172 weeks results in substantial declines in circulating B-cell subsets and in modest declines in IgG levels; these changes may serve as surrogate markers of the long-term efficacy and safety of belimumab in these patients.