Session Information
Date: Sunday, October 21, 2018
Session Title: 3S088 ACR Abstract: Spondyloarthritis Incl PsA–Clinical I: Axial SpA Epidemiology (892–897)
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose:
TNF blockers, have been widely used in immune-mediated diseases and many genetic variations predicting treatment response have been described. We applied previously published genetic variations relevant in response of TNF blockers of rheumatoid arthritis (RA) and spondyloarthritis (SpA) to predict treatment response and radiographic progression of ankylosing spondylitis (AS) patients.
Methods:
We recruited 142 AS patients from three medical centers (Guanghua, Changhai and Zhongshan hospital in China). All patients have stopped treatment for more than 6 months before we recruited them or never been treated with TNF blockers. The response to etanercept or adalimumab was evaluated at 3-month and 6-month followup visits by different criteria (BASDAI 50, ASAS20, ASAS 40, ASAS5/6, partial remission and difference of ASDAS) and 62 of AS patients were evaluated for disease activity or progression with MRI (SPARCC) and radiographic imaging. Sixty-two genetic variations were collected by searching in PUBMED. Statistical analyses included Fisher’s exact test and logistic regression analysis.
Results:
Most of key loci identified belonged to genes in the Toll-like receptor signaling pathway and other immune-relevant loci. The results showed important differences between etanercept and adalimumab when associations between genetic polymorphisms and treatment response were examined. Genetic variations in ARFGAP2 alleles showed significantly difference between responders and non-responders, especially in patients treated with etanercept (OR = 0.21, P-value = 0.0004). When ASDAS was performed as the response criterion, a SLCO1C1 allele was highly associated with treatment response (OR = 12.72, P-value = 0.0004), and in the etanercept subgroup, none of the non-responders carried it (P-value = 0.008). In addition, genetic loci in LRPAP1 had strong linkage with the variation of fat metaplasia and erosion. It was associated with the variation of erosion both in 3-month follow-up and 6-month follow-up. Genetic loci in MYOM2 was associated with the variation of backfill after 6-month treatment. IL10 were associated with ankyloses at baseline. ACE and S100A8 are significantly associated with mSASSS score of sacroiliac and spine at baseline, respectively (Table 1).
Conclusion:
Several genetic loci showed significantly differences between responders and non-responders to anti-TNF agents in AS and may also predict the MRI/radiographic inflammation and disease progression. This suggests an important role of pharmacogenomics profiling in predicting treatment response and disease progression.
Table 1 Genetic loci associated with Image progression
|
Gene |
β |
P-value |
|
|
MRI (N=65) |
|||
|
sacroiliac joint inflammation |
ARFGAP2 |
8 |
0.02 |
|
spine inflammation |
TNF |
-7.6 |
0.02 |
|
fat metaplasia |
LRPAP1 |
-1.8 |
0.004 |
|
erosion |
LRPAP1 |
1.1 |
0.006 |
|
backfill |
MYOM2 |
-1.6 |
0.003 |
|
ankylosis |
IL10 |
8.1 |
0.003 |
|
mSASSS (N=65) |
|||
|
sacroiliac |
ACE |
0.66 |
0.04 |
|
spine |
S100A8 |
11.2 |
0.01 |
To cite this abstract in AMA style:
Liu J, Pu W, Zhu Q, Fan H, Wan W, Zou H, Zhou X, Reveille JD, He D, Wang J. Pharmacogenomics Study of Predicting Response of TNF Blocker and Medical Image Progression in Chinese Han Ankylosing Spondylitis Population [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/pharmacogenomics-study-of-predicting-response-of-tnf-blocker-and-medical-image-progression-in-chinese-han-ankylosing-spondylitis-population/. Accessed March 23, 2023.« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacogenomics-study-of-predicting-response-of-tnf-blocker-and-medical-image-progression-in-chinese-han-ankylosing-spondylitis-population/