Effect of belimumab on proteinuria and anti-phospholipase A2 receptor autoantibody in primary membranous nephropathy
| Autor: | Christine Barrett, Rachel B Jones, Sophie Gisbert, Ruth M. Tarzi, Alexandra Belson, Caroline O. S. Savage, Robert B Henderson, Lisa C. Willcocks, Gengqian Cai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Population 030232 urology & nephrology Antibodies Monoclonal Humanized Gastroenterology Glomerulonephritis Membranous 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Membranous nephropathy Pharmacokinetics Internal medicine medicine Humans Prospective Studies Adverse effect education Aged Autoantibodies Transplantation education.field_of_study Creatinine Proteinuria business.industry Receptors Phospholipase A2 Remission Induction Middle Aged medicine.disease Belimumab Confidence interval 030104 developmental biology chemistry Nephrology Female medicine.symptom business Immunosuppressive Agents medicine.drug |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 35(4) |
| ISSN: | 1460-2385 |
| Popis: | BackgroundImmunosuppressant drugs reduce proteinuria and anti-phospholipase A2 receptor autoantibodies (PLA2R-Ab) in primary membranous nephropathy (PMN) with varying success and associated toxicities. This study aimed to evaluate the effect of belimumab on proteinuria and PLA2R-Ab in participants with PMN.MethodsIn this prospective, open-label, experimental medicine study, 14 participants with PMN and persistent nephrotic-range proteinuria received up to 2 years belimumab monotherapy (10 mg/kg, every 4 weeks). Changes in proteinuria (urinary protein:creatinine ratio), PLA2R-Ab, albumin, cholesterol, B-cell subsets and pharmacokinetics were analysed during treatment and up to 6 months after treatment.ResultsEleven participants completed to the primary endpoint (Week 28) and nine participants completed the study. In the intention-to-treat population population, baseline proteinuria of 724 mg/mmol [95% confidence interval (CI) 579–906] decreased to 498 mg/mmol (95% CI 383–649) and 130 mg/mmol (95% CI 54–312) at Weeks 28 and 104, respectively, with changes statistically significant from Week 36 (n = 11, P = 0.047). PLA2R-Ab decreased from 174 RU/mL (95% CI 79–384) at baseline to 46 RU/mL (95% CI 16–132) and 4 RU/mL (95% CI 2–6) at Weeks 28 and 104, respectively, becoming statistically significant by Week 12 (n = 13, P = 0.02). Nine participants achieved partial (n = 8) or complete (n = 1) remission. Participants with abnormal albumin and/or cholesterol at baseline gained normal/near normal levels by the last follow-up. Adverse events were consistent with those expected in this population.ConclusionsBelimumab treatment in participants with PMN can reduce PLA2R-Ab and subsequently proteinuria, important preludes to remission induction. |
| Databáze: | OpenAIRE |
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