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

Abstract

ObjectiveWe undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long‐term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76‐week trial (ClinicalTrials.gov identifier: NCT00410384).MethodsPatients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long‐term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels.ResultsOf 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA–SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment‐related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4‐point reduction in the SELENA–SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was −83.2%.ConclusionThese long‐term exposure results confirm the previously observed safety and efficacy profiles of belimumab in patients with SLE.

Long‐Term Impact of Belimumab on Health‐Related Quality of Life and Fatigue in Patients With Systemic Lupus Erythematosus: Six Years of Treatment

“…The largest improvements in HRQoL and fatigue were reported in the first study year of treatment and were maintained or further increased during long‐term exposure to belimumab through study year 6. Previously reported efficacy and safety data from this long‐term continuation study demonstrated an overall decrease in disease activity, along with a decrease in prednisone use, low rates of flare, and organ damage accrual and an acceptable safety profile . Taken together, these results suggest that long‐term control of disease activity with belimumab plus standard therapy results in significant benefits in both HRQoL and fatigue.…”

“…This was a multicenter continuation study (BEL112233; ClinicalTrials.gov identifier: NCT00724867) in patients with SLE who completed the 76‐week parent trial BLISS‐76 (BEL110751; ClinicalTrials.gov identifier: NCT00410384) in the US . In BLISS‐76, patients were randomized to receive belimumab 1 mg/kg intravenously (IV), 10 mg/kg IV, or placebo every 28 days and continued with standard therapy.…”

“…Briefly, adult patients with a diagnosis of SLE according to the American College of Rheumatology revised criteria who were positive for antinuclear antibodies or anti–double‐stranded DNA antibodies (anti‐dsDNA) and had a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (SELENA–SLEDAI) score of ≥6 were included. All patients who completed BLISS‐76 in the US had the option to enroll in this continuation study , which was conducted from August 5, 2008 to March 26, 2015.…”

“…The objectives of this long‐term continuation study of the phase III RCT BLISS‐76 trial in the US were to evaluate the long‐term safety and tolerability, impact on HRQoL and fatigue, and efficacy of belimumab plus standard therapy. Efficacy and safety data have been reported elsewhere . Here, we present the longer‐term HRQoL and fatigue outcomes and the impact of clinical characteristics on these outcomes.…”

Evaluation of belimumab treatment in patients with systemic lupus erythematosus in a clinical practice setting: Results from a 24-month OBSErve study in Argentina

“… 13 – 15 Short-term (up to 76 weeks) efficacy and safety of belimumab have been demonstrated in four large Phase 3 clinical trials, 16 – 19 and these safety and efficacy profiles have recently been shown to be maintained up to 7 years of belimumab treatment. 20 Currently, belimumab is indicated as add-on therapy in adult patients with active, autoantibody-positive SLE despite standard therapy (ST) 11 and with a high degree of disease activity (e.g. positive anti-dsDNA and low complement levels).…”