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Abstract: PO1885

Belimumab for the Treatment of Frequently Relapsing Nephrotic Syndrome: The BELNEPH Study

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Vivarelli, Marina, Ospedale Pediatrico Bambino Gesù – IRCCS, Rome, Italy
  • Colucci, Manuela, Ospedale Pediatrico Bambino Gesù – IRCCS, Rome, Italy
  • Gargiulo, Antonio, Ospedale Pediatrico Bambino Gesù – IRCCS, Rome, Italy
  • Bettini, Chiara, Ospedale Pediatrico Bambino Gesù – IRCCS, Rome, Italy
  • Emma, Francesco, Ospedale Pediatrico Bambino Gesù – IRCCS, Rome, Italy
Background

A pathogenic role of B cells in pediatric idiopathic nephrotic syndrome (INS) has been suggested by the therapeutic efficacy of B-cell depletion, which however can impair immune memory. Belimumab treatment affects B-cell survival and differentiation but preserves the established immune memory. Its efficacy has been proven in other immune-mediated diseases, such as systemic lupus erythematosus and membranous nephropathy.

Methods

In this open-label, prospective, single-arm study, 5 children with frequently-relapsing INS who were on alternate-day prednisone only were enrolled. Belimumab was administered at 10 mg/kg i.v. on day 0, 14, 28 and then every 4 weeks for up to 12 months. Concomitant prednisone treatment was gradually tapered up to recurrence of NS if it occurred. Safety, efficacy and laboratory blood and urine parameters were monitored for the duration of the study.

Results

Four patients completed the primary endpoint (6 months) and 2 patients completed the study. Infusions were well tolerated. One patient experienced a pulmonary infection which required hospitalization 2.3 months after the first infusion. Four patients experienced a first relapse within 6 months (1.9, 2.5, 2.6, 3.3 months after starting treatment) and 1 patient 8.1 months from first infusion. Three patients discontinued the study due to the frequency of relapses (≥2) after 5.2, 9.2, 9.6 months, respectively, and were started on another steroid-sparing agent. The study was discontinued due to apparent lack of effectiveness.
CD19+ B cells decreased during the follow-up, with a nadir at 6 months (8.6% of lymphocytes vs 19.1% at baseline, p<0.01). Naïve B cells started to significantly decrease after 1 month (7.7% vs 12.4% at baseline, p<0.05) and continued to decline during the follow-up. In contrast, no significant impact was observed on memory B cells, which became the most representative B-cell subset already at 1 month (43.5% of B cells vs 27.3% at baseline, p<0.01), with an initial shift toward a switched subset (57.4% and 59.0% of memory B cells at 3 and 6 months, respectively, vs 48.3% at baseline, p<0.01). Serum IgG, IgA and IgM levels were not significantly modified.

Conclusion

Belimumab treatment in children with frequently-relapsing INS failed to modify disease course. Persistence of circulating memory B cells supports their pathogenic role in INS.

Funding

  • Private Foundation Support