Session Information
Session Type: Late-Breaking Abstracts
Background/Purpose: A primary clinical goal of RA in treating to target (T2T) is to improve long term outcomes including the control of symptoms and prevention of structural damage. Acute phase reactants inform inflammation, which “uncouples” from radiographic progression where markers of ongoing joint damage processes can assist T2T strategies. 14-3-3η is a mechanistic marker that is associated with radiographic progression and up-regulates deleterious factors such as VCAM-1 and TNFα while potently inducing IL-6.[1]This study evaluates longitudinal serum 14-3-3η expression in 148 RA patients in 4 treatment groups to examine how 14-3-3η may inform response monitoring and joint damage.
Methods: 298 serum samples from 149 Japanese patients with established RA were tested for 14-3-3η (cut-off ≥0.19 ng/ml) prior to, and 1-year after treatment initiation. 49 received adalimumab (ADA), 23 methotrexate (MTX), 50 tocilizumab (TOC), and 27 tofacitinib (Tofa). Radiographic progression was assessed with annual change in Sharp-van der Heijde score (SHS). 86% were female, median age was 60 years and disease duration was 51 weeks. The Mann-Whitney U-test was used to assess differences between groups and the Wilcoxon matched pairs signed rank test for significance of changes in 14-3-3η. A ROC curve was generated for differential 14-3-3η baseline expression and DAS remission. The Fisher exact test provided the strength of association of 14-3-3η year 1 status with DAS categorization and radiographic progression (ΔSHS>0.5).
Results: At baseline, 110 patients (74%) were 14-3-3η +ve and had higher disease severity than -ve patients; DAS28 [5.6 vs. 4.8, p=0.01], CDAI [24.7 vs. 16.0, p=0.02], SDAI [26.8 vs. 18.8, p=0.02], TJC28 [7.0 vs. 5.0, p=0.03], SJC28 [6.5 vs. 4.0, p=0.05], ESR [48 vs. 35, p=0.05], RF [85 vs. 16, p<0.0001], and ACPA [100 vs. 17, p=0.0002]. Across the whole cohort, and within each treatment group, median 14-3-3η decreased significantly by year 1 [0.70 vs. 0.37 ng/ml, p<0.0001]; ADA [0.62 to 0.38 ng/ml, p=0.0001], MTX [0.67 to 0.33 ng/ml, p=0.01], TOC [0.43 to 0.27, p=0.0007] and Tofa [1.30 to 1.26 ng/ml, 0.01]. The TOC group was the only one where 14-3-3η was differentially expressed at baseline between patients in DAS remission and non-remission (0.23 vs. 4.02 ng/ml, p=0.008) delivering a ROC AUC of 0.72 [95% CI=0.57-0.87], and specificity/sensitivity of 85%/70% at a cut-off of ≤0.40 ng/ml. At year 1, 97 patients (65%) were 14-3-3η +ve. Of the 110 baseline +ve patients, 18 had levels that decreased below the 14-3-3η +ve cut-off and a significant association emerged between '-ve 14-3-3η year 1 status' and DAS28 categorical distribution (Chi-sq=11.0, p=0.018) as well as '+ve year 1 status' with radiographic progression (Chi-sq=3.7, p=0.05).
Conclusion: Positive 14-3-3η baseline status corresponds with more severe RA and a post-treatment decrease, to negative levels, at year 1 corresponds with DAS28 remission and better radiographic outcomes. As a potent inducer of IL-6, 14-3-3η at baseline predicts response to tocilizumab therapy and should be investigated as a mechanistic companion biomarker for treatment selection and monitoring.
1. O’Mahony A et al. ACR2014. Poster 1950.
Disclosure:
S. Hirata,
None;
K. Hanami,
None;
A. Marotta,
Augurex Life Sciences Corp.,
3;
Y. Tanaka,
BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbvie and Daiichi-Sankyo,
2,
UCB, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD and Asahi Kasei,
5,
UCB, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD and Asahi Kasei,
8.
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