Richard A. Furie
A multicenter continuation of a phase 3 study confirmed that long-term treatment with belimumab in patients with systemic lupus erythematosus is safe and efficacious, according to findings published in Arthritis and Rheumatology.
“Belimumab was the first drug approved for systemic lupus via the traditional route of placebo-controlled trials,” Richard A. Furie, MD, of Northwell Health and the Hofstra Northwell School of Medicine, in Great Neck, N.Y., told Healio Rheumatology. “After the completion of both the phase 2 study and phase 3 studies, open-label extension studies allowed patients to continue on drug. While there were no comparators, these studies provided additional insights into safety and efficacy of long-term belimumab exposure.”
Furie and colleagues conducted a 7-year continuation study of the phase 3 BLISS-76 trial, which demonstrated the safety and efficacy of belimumab (Benlysta, GlaxoSmithKline) among patients with autoantibody-positive, active systemic lupus erythematosus (SLE).
Belimumab is safe and efficacious in patients with systemic lupus erythematosus, according to researchers.
“It is quite unusual for sponsors to invest in long-term extensions, especially after drug approval,” Furie said.
In the BLISS076 study, participants were randomly selected to receive an IV dosage of belimumab 1 mg/kg, IV belimumab 10 mg/kg or placebo, plus standard of care, for 76 weeks. To determine the long-term safety and efficacy of belimumab in patients with SLE, the researchers continued those dosages in 268 patients who had completed BLISS-76 through week 72, with patients who previously received placebo instead treated with belimumab 10 mg/kg.
Among the participants, 140 completed the continuation study. The study’s primary outcome measures were long-term safety, evaluated every 48 weeks, as well as the SLE Responder Index, flare rates, prednisone use and B cell levels.
According to the researchers, the mean Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) score at baseline was 7.8 (SD = 3.86), while the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score was 1.2 (SD = 1.51). The number of adverse effects remained stable or declined through 7 study years. During that same time, the mean SDI score increased 0.4 (SD = 0.68) from baseline. In addition, the researchers noted an SLE Responder Index response in 41.9% of participants at the study year 1, and 75.6% of patients at study year 7.
Also at the study year 7 midpoint, 78.2% of patients demonstrated a 4-point or more SELENA-SLEDAI score reduction compared with baseline, and 98.4% of patients had no new British Isles Lupus Assessment Group 1A/2B organ domain scores. In addition, 93.7% had no worsening in Physician's Global Assessment, and 20.6% experienced at least one severe SFI flare, according to the researchers. The researchers also reported a 31.4% mean decrease in prednisone dose, and an 83.2% decrease in the median amount of CD20+ B cells.
“This study confirmed the safety and efficacy profiles of belimumab,” Furie said. “Prednisone usage over time decreased, and damage accrual over the course of the extension was relatively low. Improvement in DNA antibody levels as well as complement C3 and C4 concentrations were observed. Unique to this long-term extension was the collection of B lymphocyte subset data, which demonstrated marked reductions over time.”
According to Furie, there are major unmet therapeutic needs for patients with SLE.
“The success of the belimumab program not only yielded a drug for patients, but it proved that the incredibly challenging path to approval could be overcome,” he said. “The phase 3 belimumab studies and the extension studies have served as an important foundation for other sponsors developing yet additional therapies for SLE patients.” – by Jason Laday
Disclosure: Furies reports receiving consulting fees, research grants and clinical studies from GSK. See full study for additional authors’ disclosures.