In pediatric patients with frequently relapsing nephrotic syndrome (FRNS), the therapy was well tolerated, but did not lead to significant changes in disease course.
A new report suggests that despite being well tolerated, Benlysta (belimumab) does not lead to significant clinical benefits in children with frequently relapsing nephrotic syndrome (FRNS).
The findings are based on a small study that was terminated at the interim evaluation after the therapy failed to make a meaningful impact on the number of relapses experienced by patients.
The study was published in Pediatric Nephrology.
As many as 16.9 of 100,000 children have a form of idiopathic nephrotic syndrome, which is characterized by increased permeability of the glomerular filtration barrier. In some cases, patients experience frequent relapses and require treatment with corticosteroids; sometimes they may even require immunosuppressive agents, explained the study’s authors.
In recent years, they wrote, the successful use of the anti-CD20 monoclonal antibody rituximab (Rituxan) has suggested that B cells play an important role in idiopathic nephrotic syndrome. However, the therapy can lead to prolonged hypogammaglobulinemia and impaired vaccine competence in children. The authors therefore wanted to find out if belimumab, a monoclonal immunoglobulin G1λ antibody that targets B-cell activating factor, might be safe and effective at reducing the number of relapses experienced by children with FRNS.
The investigators designed an open-label, prospective, single-arm study to treat 10 children with FRNS with intravenous belimumab for 12 months while tapering and stopping prednisone.
Seven patients were screened for inclusion in the study, but only 5 were enrolled after 2 patients declined due to the burden of monthly infusions. Of the 5 enrolled patients, 4 reached the 6-month end point and 2 of those 4 patients reached the 12-month end point. The infusions themselves were well tolerated, with no patients experiencing allergic reactions.
However, the therapy did not appear to make a meaningful clinical difference.
Three patients experienced 2 or more relapses while taking the treatment, so they were withdrawn from the study to allow the patients to take additional immunosuppression. The authors said belimumab did not spark statistically significant benefits either in terms of reducing relapses (1.4 in the 6 months on therapy vs 2.0 in the 6 months before therapy; P = .21) or in terms of reducing the cumulative prednisone dose taken by patients (1.86 vs 2.62 g/m2; P = .17).
At the interim analysis, the study’s steering committee chose to end the study.
“In conclusion, whereas well tolerated, belimumab treatment administered [intravenously] for up to 12 months in children with FRNS fails to modify disease course significantly,” the authorss concluded.
A follow-up analysis showed total and mature-naive B cells were reduced in the patients, but there was no change in memory B cells.
“Failure of belimumab to maintain prolonged steroid-free remission adds to the notion that the memory B-cell compartment has a prominent role in the pathogenesis of the disease,” the authors noted.
They said the data suggest the therapy is safe, and it is possible it might have more positive benefits over a longer time horizon. They said their patient population was too small to draw firm conclusions. Yet, the burden of monthly infusions of the therapy, combined with its apparent lack of benefit, suggest the burdens may outweigh any benefits. They said future investigation of the role of memory B cells in disease pathogenesis is warranted.
Vivarelli M, Colucci M, Gargiulo A, Bettini C, Lo Russo A, Emma F. Belimumab for the treatment of children with frequently relapsing nephrotic syndrome: the BELNEPH study Pediatr Nephrol. Published online August 5, 2021. doi:10.1007/s00467-021-05175-9