Belimumab for the treatment of children with frequently relapsing nephrotic syndrome: the BELNEPH study

Background: Effectiveness of rituximab in pediatric idiopathic nephrotic syndrome suggests that B cells play a pathogenic role. We tested safety and efficacy of the B-cell-modulating agent belimumab in frequently relapsing nephrotic syndrome (FRNS).

Methods: An open-label, prospective, single-arm pilot study (EUDRACT 2017-003839-11) was designed to treat 10 children with FRNS with i.v. belimumab for 12 months. Prednisone was tapered/stopped. Safety, number of relapses, cumulative prednisone dose and B-cell subset "levels" are referred to both B cell subset and immunoglobulin.

Results: Five patients were enrolled, and four reached the primary 6-month endpoint. Of these, two completed the 12-month endpoint. Three patients experienced ≥2 relapses while on belimumab, requiring additional immunosuppression. Compared to the 6 months before belimumab treatment, the mean number of relapses (1.4 vs. 2, p=0.21) and the mean cumulative prednisone dose (1.86 vs. 2.62 g/m², p=0.17) were not significantly reduced during the 6 months on belimumab. This study was terminated by the steering committee after the interim evaluation because belimumab failed to show clear benefits to counterbalance the inconvenience of monthly i.v. infusion. During follow-up, total and mature-naïve B cells decreased, while no change in memory B-cells was observed. Serum immunoglobulins remained stable. No infusion reaction was observed.

Conclusions: Short-term treatment with belimumab in pediatric FRNS was well tolerated. The number of patients was too small to draw conclusions on efficacy. Nonetheless, we did not observe clear improvements. The burden of monthly in-hospital i.v. infusions outweighed potential benefits. Persistence of circulating memory B cells supports their pathogenic role in the disease. A higher resolution version of the Graphical abstract is available as Supplementary information.