Disease Control and Safety of Belimumab Plus Standard Therapy Over 7 Years in Patients with Systemic Lupus Erythematosus

Abstract

Objective.To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years (n = 177 currently ongoing).Methods.Patients (n = 345) who completed a double-blind, placebo-controlled, 52-week study of belimumab 1, 4, or 10 mg/kg and 24-week extension of belimumab (placebo switched to 10 mg/kg; belimumab same dose or switched to 10 mg/kg) could receive belimumab 10 mg/kg in an open-label continuation study (n = 296). Disease activity was analyzed in patients with active SLE at baseline of the initial study. Biomarker and SLE medication changes were evaluated, and adverse events (AE) were monitored throughout the study.Results.Total belimumab exposure over 7 years (double-blind and open-label periods): 1746 patient-years. SLE Responder Index (SRI) response rates at Week 52 in autoantibody-positive patients: placebo, 29%; belimumab, 46% (p < 0.05). In the continuation study, 57% of auto-antibody-positive patients had an SRI response by Year 2 and 65% by Year 7; severe flares occurred in 19% with placebo and 17% with belimumab during the first year, with the annual rate declining to 2%–9% during years 2–7. Anti-dsDNA autoantibodies in patients positive for them at baseline had a progressive decline of 40%–60% from baseline over 2–7 years with belimumab. Corticosteroid use decreased over time with ≥ 50–55% reduction in median dose during years 5–7. Serious and overall annual AE rates, including infections, were generally stable or decreased during 7-year treatment.Conclusion.Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years. [ClinicalTrials.gov numbers: NCT00071487 and NCT00583362]

Long‐Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus

“…In the present study, three‐fourths of patients were SRI responders at the study year 7 midpoint, an observation that is consistent with the phase II continuation study, in which 65% of patients had achieved an SRI response by study year 7 (73% in the completer analysis) 12.…”

“…In this continuation study, the percentage of patients experiencing a new severe SFI flare between the study year 1 and study year 7 midpoints was low; the cumulative count increased from 15 of 267 patients (5.6%) to 55 of 267 patients (20.6%) during this period. In the phase II continuation study, the percentages of severe flares were also low, decreasing from 7% to 2% across each year of belimumab treatment 12.…”

“…Belimumab binds to and inhibits the activity of soluble human B lymphocyte stimulator protein 10. A placebo‐controlled phase II study showed that intravenous (IV) belimumab plus standard therapy was generally well tolerated 11; a good safety profile was maintained over 7 years 12. Two phase III studies, the Study of Belimumab in Subjects with SLE 52‐week (BLISS‐52) and 76‐week (BLISS‐76) trials, demonstrated the safety and efficacy of belimumab in patients with autoantibody‐positive, active SLE 13, 14.…”

Upcoming biological therapies in systemic lupus erythematosus

“…The results remain positive with a maintained reduction in corticosteroid use and low rates of adverse effects in a seven-year follow up of lupus patients treated with belimumab [20].…”

When to use belimumab in SLE

“…Importantly, relevant real-life experience [4,6,7,9] as well as a 7-year long-term extension study involving patients coming from the phase 2 RCT who had had an improvement in physician global assessment (PGA) since baseline proved a long-standing disease control and decrease in flare rate during the overall 7-year observation on belimumab treatment [17], suggesting such positive effects are long-lasting. Notably, published studies including RCT, long-term extensions studies and real-life experience underlined a good safety and tolerability profile of belimumub use even when added to immunosuppressive therapy.…”