Abstract: TH-PO639
Safety and Efficacy of Anifrolumab Therapy to Reduce Proteinuria in APOL1-Associated Lupus Nephritis
Session Information
- Lupus Nephritis: Clinical, Outcomes, and Therapeutics
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Tumlin, James A., Emory University, Atlanta, Georgia, United States
- Sanchez, Lorin M., Emory University, Atlanta, Georgia, United States
- Virmani, Sharad, Emory University, Atlanta, Georgia, United States
- Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Group or Team Name
- NephroNet Clinical Trials Group.
Background
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disorder that leads to Lupus nephritis (LN) in up to 40% of patients. High type I interferon gene signatures (IFNGS) are present in approximately 80% of patients with LN and are associated with higher rates of treatment failure. Previous studies using the interferon alpha receptor antagonist Anifrolumab to treat Lupus nephritis failed to demonstrate a reduction in UP/Cr at 52 weeks. Because dual expression of APOL-1 “at-risk” alleles in LN is associated with progressive disease, we examined the efficacy of Anifrolumab in LN with varying APOL-1 gene expression.
Methods
Prospective, open-labeled study of 11 patients with confirmed Lupus nephritis with UP/Cr > 500 mg/gm after 6 months of induction immunosuppressive therapy. All patients were maintained on mycophenolate and RAAS therapy for 4 weeks prior to Anifrolumab. All patients were screened for APOL-1 status. Serial UP/Cr and eGFR measurements were collected and reported as Means + SEM.
Study Inclusion Criteria 1) APOL-1 testing prior to Anifrolumab infusion; 3) UP/Cr > 500 mg/gm; 5) CKD-Epi eGFR >30 mls/min/1.73M2 4) and active immunosuppression.
Definitions: A complete response was defined as UP/Cr < 500 mg/gm after 6 months. A partial response was defined as > 50% reduction from pre-study UP/Cr.
Results
Data from this study are presented in Table-1. Of the 11 enrolled patients 3 had dual APOL-1 at risk alleles and 3 with a single allele. Five patients had no at risk alleles. A six month course of Anifrolumab (300 mg) induced a complete or partial remission in 73% of the total and 66% among dual or single allele LN patients. Both single and dual APOL-1 patients had higher baseline UP/CR compared to wild-type patients. There were no major infections or hospitalizations
Conclusion
Anifrolumab significantly reduced UP/Cr in LN patients with dual, single or no APOL-1 "at risk alleles. Over 60% of dual or single allele LN patients achieved a complete or partial response. Larger studies in this high risk population will be needed to confirm these results.
Table-1
| Table-1 | % Lupus FSGS | Baseline UP/Cr | Post UP/Cr | Baseline eGFR | Post eGFR |
| Total Population | 64% | 5091 mg/gm | 1317 mg/gm * | 59 mls/min | 50 mls/min |
| APOL 2 Alleles | 100% | 8788 mg/gm | 1847 mg/gm | 46 mls/mi | 50 mls/min |
| APOL 1 Allele | 80% | 6243 mg/gm | 2146 mg/gm ^ | 50 mls/min | 51 mls/min |
| APOL 0 allele | 20% | 1463 mg/gm | 531 mg/gm | 63 mls/min | 56 mls/min |
* P<0.028 ^P<0.032
Funding
- NIDDK Support