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Federico Alberici, Rona Smith, Mariana Fonseca, Lisa Willcocks, Rachel Jones, Julia Holle, Stefan Wieczorek, Thomas Neumann, Davide Martorana, Gina Gregorini, Renato A Sinico, Annette Bruchfeld, Iva Gunnarsson, Sophie Ohlsson, Bo Baslund, Vladimir Tesar, Zdenka Hruskova, Maria Cid, Augusto Vaglio, Paul Lyons, Ken Smith, David Jayne, MO040
ASSOCIATION OF A TNFSF13B (BAFF) REGULATORY REGION SINGLE NUCLEOTIDE POLYMORPHISMS WITH RESPONSE TO RITUXIMAB IN ANCA-ASSOCIATED VASCULITIS, Nephrology Dialysis Transplantation, Volume 31, Issue suppl_1, May 2016, Pages i45–i46, https://doi.org/10.1093/ndt/gfw137.02Close - Share Icon Share
Introduction and Aims: Rituximab (RTX) is effective for induction and maintenance of remission in ANCA-associated vasculitis (AAV); however relapse is common after discontinuation and predictors of response do not exist. This study assesses potential genetic determinants of response to RTX in AAVs.
Methods: Genotyping of 18 candidate single nucleotide polymorphisms (SNPs), chosen according to a biological rationale, was performed using TaqMan and Sequenom platforms. The end points were RTX-failure (RF) risk 6 months after RTX and time to RF. Bonferroni correction was applied.
Results: 213 patients were enrolled in the primary and 109 in the replication cohorts. A SNP in the TNFSF13B gene region (BAFF) was associated to time to RF in the primary (HR 12.4, p=7x10-04) and replication cohorts (HR 5.4, p=0.002). Meta-analyses showed an association with both end-points. Carriers of the risk genotype had higher rate of detectable B cells 6 months after RTX (50%vs14%, p=0.02). This association was restricted only to PR3-ANCA patients (RF-risk at 6 months OR 9, p=0.01; time to RF HR 8.2, p=8.7x10-06) while in the MPO-ANCA subgroup an association with a SNP in the IL2-IL21 region was identified but restricted only to the primary cohort (RF risk at 6 months and time to RF respectively p=0.03 and p=0.02).
Association results for the SNP in the regulatory BAFF region and the 2 outcomes.
| Outcome . | Primary cohort . | Secondary cohort . | Meta-analysis . | |||
|---|---|---|---|---|---|---|
| . | OR-HR . | p . | OR-HR . | p . | OR-HR . | p . |
| RF risk at 6 months | 9.1 | 0.07 | 8.6 | 0.009 | 8.8 | 0.007 |
| Time to RF | 12.4 | 7.4x10-4 | 5.4 | 0.002 | 7.3 | 8.5x10-6 |
| Outcome . | Primary cohort . | Secondary cohort . | Meta-analysis . | |||
|---|---|---|---|---|---|---|
| . | OR-HR . | p . | OR-HR . | p . | OR-HR . | p . |
| RF risk at 6 months | 9.1 | 0.07 | 8.6 | 0.009 | 8.8 | 0.007 |
| Time to RF | 12.4 | 7.4x10-4 | 5.4 | 0.002 | 7.3 | 8.5x10-6 |
Association results for the SNP in the regulatory BAFF region and the 2 outcomes.
| Outcome . | Primary cohort . | Secondary cohort . | Meta-analysis . | |||
|---|---|---|---|---|---|---|
| . | OR-HR . | p . | OR-HR . | p . | OR-HR . | p . |
| RF risk at 6 months | 9.1 | 0.07 | 8.6 | 0.009 | 8.8 | 0.007 |
| Time to RF | 12.4 | 7.4x10-4 | 5.4 | 0.002 | 7.3 | 8.5x10-6 |
| Outcome . | Primary cohort . | Secondary cohort . | Meta-analysis . | |||
|---|---|---|---|---|---|---|
| . | OR-HR . | p . | OR-HR . | p . | OR-HR . | p . |
| RF risk at 6 months | 9.1 | 0.07 | 8.6 | 0.009 | 8.8 | 0.007 |
| Time to RF | 12.4 | 7.4x10-4 | 5.4 | 0.002 | 7.3 | 8.5x10-6 |
Conclusions: We have identified a SNP that may predict response to RTX in AAV. Its proximity to the BAFF region and the higher proportion of detectable B cells 6 months after RTX in the carrier of the unfavourable genotype, may suggest a role for this SNP in modulating BAFF levels.
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