Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
Dr. Joan T. Merrill
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
Dr. George Bertsias
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.