Add-on therapy with the monoclonal antibody belimumab (Benlysta) was effective among patients with systemic lupus erythematosus (SLE) receiving standard of care treatment in China, Japan, and South Korea, a phase III study found.
Among 677 patients with active disease who were also being treated with conventional therapies such as steroids and antimalarials, the primary endpoint of a 4-point decrease on the SLE Responder Index 4 (SRI4) was met at week 52 by 53.8% of patients randomized to receive belimumab compared with 40.1% of those given placebo, according to Fengchun Zhang, MD, of Peking Union Medical College Hospital in Beijing Shi, China, and colleagues.
Accordingly, the odds ratio for meeting that endpoint was almost doubled with belimumab, at 1.99 (95% CI 1.40-2.82, P<0.0001), the researchers reported in Annals of the Rheumatic Diseases.
Belimumab targets the B lymphocyte stimulator protein, which is essential to B-cell proliferation and survival, and is approved in the United States and Europe for patients with autoantibody-positive SLE.
Three international phase III trials conducted primarily in the Americas and Europe demonstrated the safety and efficacy of belimumab.
In 2009, the Chinese SLE Treatment and Research Group established a registry to determine the clinical characteristics of SLE in the Chinese population, and have found some major differences compared with cohorts enrolled in the United States and Europe. These included a greater prevalence of hematologic complications and renal involvement, and a lower incidence of neurologic manifestations.
Therefore, because there were few patients from Northeast Asia in the previous belimumab trials and it’s unclear if differences in efficacy or safety would be seen in this population, Zhang and colleagues conducted a study in 49 centers in China, Japan, and South Korea from 2011 to 2015.
Participants had a disease activity score of 8 or higher on the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), had a positive test for antinuclear antibodies, and were on stable regimens of standard SLE medications.
More than three-quarters of patients were from China, and 90% were women. Mean age was 32, and mean disease duration was 6 years. Mean SELENA-SLEDAI was 10.
Along with the primary endpoint, significant improvements also were seen for several secondary endpoints. For instance, 55.7% of patients on belimumab had a decrease of at least 4 points on the SELENA-SLEDAI at week 52 compared with 42.2% of those on placebo (OR 2, 95% CI 1.41-2.83, P=0.0001), and the proportion having a decrease of 7 or more points was higher in the belimumab group than the placebo group (32.4% vs 23.5%, OR 1.76, 95% CI 1.13-2.74, P=0.0116).
In addition, a 50% lower risk of severe flare was seen with belimumab compared with placebo (12% versus 22.1%, HR 0.50, 95% CI 0.34-0.73, P=0.0004). “Interestingly, when severe flares occurred in the belimumab group, they occurred early in the study, possibly before the full belimumab effect was observed,” the investigators commented.
The cumulative prednisone dose over 52 weeks also was lower in the belimumab group, at a median of 4,190 mg, compared with the placebo group, at 4,758.1 mg (P=0.0005). “This study builds on findings from previous studies, which suggest that belimumab has a corticosteroid-sparing effect,” they noted.
With regard to safety, the overall rate of adverse events was similar in the belimumab and placebo groups, and while the incidence rate of serious adverse events was higher in the placebo group (18.3% versus 12.3%), the rate of infectious serious adverse events was similar (5.3% and 5.5%).
The investigators also considered adverse events of special interest, including malignancies, post-infusion systemic reactions, depression/suicide/self injury, and deaths, finding similar rates between the belimumab and placebo groups. In the belimumab group, there were no suicide attempts or completed suicides, although there was one case of suicidal ideation. In the placebo group, there was one suicide attempt.
One patient on belimumab developed cervical carcinoma, and one patient receiving placebo died of respiratory failure that was considered unrelated to treatment.
Limitations of the study included the exclusion of pediatric patients and those with severe kidney or central nervous system involvement. In addition, the possibility of unusual adverse events can’t be ruled out until more patients receive belimumab for longer periods.
“Despite these limitations, the study provides valuable information about the effect of belimumab treatment in a Northeast Asian population of patients with active, antibody-positive SLE,” Zhang and colleagues concluded.
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