The study, “Efficacy and safety of subcutaneous belimumab in anti‐dsDNA‐positive, hypocomplementemic patients with systemic lupus erythematosus,” was published in the journal Arthritis & Rheumatology.
GSK’s Benlysta is an approved immunotherapy, injected intravenously or under the skin (subcutaneous), for patients with active disease, and positive for autoantibodies — a recognized biomarker for SLE — receiving standard treatment.
The subcutaneous formulation was approved by the U.S. Food and Drug Administration in 2017, based on positive results from the Phase 3 BLISS-SC trial (NCT01484496), involving 836 adult, autoantibody-positive lupus patients who were on corticosteroids — a standard therapy.
“Intravenous administration of belimumab is an obstacle to treatment for many patients due to the need to go to the hospital for drug infusions. Thus, a higher number of patients could benefit from this treatment,” Andrea Doria, MD, the study’s first author from the University of Padova in Italy, said in a press release.
Previous studies evaluating the effectiveness of the intravenous Benlysta formulation found that lupus patients with low levels of complement components, or hypocomplementemic — an indicator of immunodeficiency and susceptibility to infections, associated with SLE — and anti-dsDNA autoantibodies at baseline had greater improvements than people without these characteristics.
In this analysis, researchers evaluated both the effectiveness and safety of subcutaneous Benlysta in that specific subset of patients — considered to have high disease activity — who participated in the BLISS-SC trial. They also assessed improvements in fatigue through the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score.
The double-blind, placebo-controlled Phase 3 trial randomly assigned patients to weekly subcutaneous injections of either 200 mg of Benlysta or a placebo, in addition to standard therapy. For each patient taking placebo, two patients were assigned Benlysta.
The primary goal was reduction of disease activity after 52 weeks of treatment, assessed through the SLE Responder Index 4 (SRI4). Secondary goals included time to first severe disease relapse, and reduction in corticosteroid dose.
Among the BLISS-SC study participants, 356 patients — 248 receiving Benlysta and 108 on placebo — were hypocomplementemic and had anti-dsDNA autoantibodies, and were included in the analysis. Patients’ mean age was 34.6 years in both groups, and most of them were women.
Disease activity was reduced in significantly more patients receiving Benlysta (64.6%) than in those in the placebo group (47.2%), and a significant difference between the two groups was observed as early as week 16.
Benlysta treatment also reduced the occurrence of severe relapses and the need for corticosteroids, and improved patients’ fatigue levels, compared with placebo.
Adverse effects of Benlysta therapy were similar to those in the placebo group, and consistent with the therapy’s known safety profile.
The team noted that, compared with the overall data of the BLISS-SC study, this subpopulation showed a slightly increased response rate in the Benlysta group and a modestly decreased response rate in the placebo group, suggesting these patients may be more difficult to treat with standard therapies.
“Such results, along with those of the primary study [BLISS-SC study], provide substantial support for the introduction of SC belimumab, especially in patients with SLE who are hypocomplementemic and anti-dsDNA positive,” the researchers wrote.
The mortality rates of this severe, predominately female, chronic inflammatory disease remain high, compared with non-lupus causes of death. However, lupus is not included in mortality statistics the Centers for Disease Control and Prevention (CDC) uses to create its annual list of leading causes of death in the United States.
This cause-of-death ranking is a useful tool for assessing the health of the U.S. population and the relative burden of specific diseases.
In an accompanying report, “Lupus — An Unrecognized Leading Cause of Death in Young Women: Population‐based Study Using Nationwide Death Certificates, 2000‐2015,” in the same journal, researchers ranked lupus deaths among CDC’s leading causes of death to determine the relative burden of these deaths in women.
In 2000-2015, 28,411 women died from a lupus-associated cause in the U.S. Lupus was found to be the 15th leading cause of death in the 10-14-year age group, 10th in the 15-24-year age group, and 14th in the 25-34-year and 35-44-year age groups.
Among black and Hispanic women, lupus ranked fifth in the 15-24-year group, sixth in the 25-34-year group, and eighth-ninth in the 35-44-year age group, when analyzing only disease-associated deaths.
Researchers noted these numbers may even be underestimations, because lupus may not be recorded as the cause of death in as many as 40 percent of lupus patients. This may be a result of limited awareness of lupus-associated complications and the misperception that they’re unrelated to the disease.
“The recognition of SLE as a leading cause of death may influence physicians’ coding on death certificates, CDC reporting of death burden, government policy, and government research funding, which may eventually help in reducing the disease burden of SLE,” the team wrote.