Background/Purpose: Serum 14-3-3η is a diagnostic marker for RA. Recent in vitro evidence indicates that it may play a casual role in the pathogenesis of RA. As such the clinical usefulness of 14-3-3η is being more extensively investigated to include prediction of RA in arthralgia subjects and efficacy of drugs used to treat RA. In this study, we investigated whether serum 14-3-3η level is useful as a marker to predict therapeutic efficacy of tocilizumab (TCZ) in RA.

Methods: Sera 14-3-3η were measured in 41 patients (median age 54 yrs, range 20–78 yrs) with RA before and 3, 6, and 12 months after treatment with TCZ (8 mg/kg iv every 4 weeks), using the 14-3-3η ELISA kit (Augurex). 14-3-3η positivity was defined as ≥ 0.19 ng/ml. Median DAS28-ESR (DAS28) and clinical disease acrivity index (CDAI) before treatment were 5.1 (range 2.1–7.5) and 22.7 (range 10.4–60.8), respectively. 31 of 41 patients were ACPA positive, 37 were MMP3 positive and 1 was negative for both markers. Mann-Whitney U-tests and Fisher’s exact tests were performed for comparison between treatment groups. A regression analysis was performed to determine if serum 14-3-3η was an independent predictor of diseases activity scores by comparison to DAS28 and CDAI.

Results: At pre-treatment, 28 of 41 patients were 14-3-3η positive and the 14-3-3η positive group tended to have higher baseline DAS28 (4.5 vs 5.3, p = 0.055) and CDAI (20.0 vs 25.4, p = 0.046). The 14-3-3η levels were significantly lower post-treatment with TCZ (4.7 vs 3.7, p = 0.028). The patient group with decreased 14-3-3η after 3months of treatment had significantly greater changes in MMP3 levels compared to the group with no decrease (54.8 vs 8.0, p = 0.027). According to the EULAR response criteria, the good responder group (n = 17) had significantly lower pre-treatment 14-3-3η levels compared to the moderate and non-responder group (n = 24), 0.37 vs 1.76 ng/ml, p = 0.0252. Similarly, the pre-treatment 14-3-3η levels were significantly lower in the group of patients that achieved remission by DAS28 < 2.6 and CDAI ≤ 10 (as remission and low diseases activity), after treatment. Neither ACPA nor MMP-3 levels were different between these responder groups. Fisher’s exact testing revealed an association (p = 0.045) between DAS28 remission and 14-3-3η negativity delivering an odds ratio (OR) of 3.4 (95% CI: 0.9–13.3). Regression analysis controlling for baseline DAS28 revealed that 14-3-3η levels were an independent predictor of remission yielding a likelihood ratio (LR) of 7.8, p= 0.0052.

Conclusion: Serum 14-3-3η is a potential marker for predicting efficacy of TCZ treatment for RA. Further study is being achieved to establish the usefulness of 14-3-3η in longer term administration of TCZ.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-usefulness-of-periodic-detection-of-serum-14-3-3i%c2%b7-for-predicting-efficacy-of-tocilizumab-in-ra/