Serum 14-3-3η as predictor of clinical remission and progression of structural damage in early rheumatoid arthritis following a treat-to-target strategy in a randomized controlled trial

Abstract

Objective

14-3-3η is a proinflammatory mediator critical to joint destruction in rheumatoid arthritis (RA). We aimed to evaluate serum 14-3-3η for predicting disease activity and radiographic progression in patients with early RA in the double-blinded, randomized OPERA trial.

Method

180 patients with early RA were randomized to receive methotrexate (MTX) + adalimumab or MTX + placebo in combination with glucocorticoid injections into swollen joints. Disease activity was measured using the 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP). Clinical remission was defined as DAS28-CRP < 2.6. X-rays of hands and feet were evaluated by the Total Sharp van der Heijde score (TSS). Radiographic progression was defined as exceeding the smallest detectable change (1.8 TSS-units). Serum 14-3-3η was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression models were used to identify predictors of DAS28-CRP remission at 6 months and radiographic progression at 12 months.   

Results

Baseline 14-3-3η was a borderline significant independent predictor of radiographic progression at 12 months (odds radio = 1.02, 95% confidence interval 1.00–1.03, p = 0.05). In anti-cyclic citrullinated peptide antibody (ACPA)-negative patients, a moderate/high baseline 14-3-3η concentration increased the risk of radiographic progression at 12 months [4/51 (8%) vs 3/9 (33%), χ2 = 4.823, p = 0.028]. No value of 14-3-3η for predicting achievement of clinical remission was found.        

Conclusion

Serum 14-3-3η was a borderline significant predictor of radiographic progression, particularly in ACPA-negative patients, but not of predicting achievement of clinical remission. Optimal cut-off levels of 14-3-3η for predicting radiographic progression in RA need further clarification.

Acknowledgements

Augurex Life Sciences Corp, Vancouver, Canada, is acknowledged for donating the immunoassay kits for 14-3-3η analyses. For the OPERA trial, AbbVie Denmark A/S provided adalimumab and placebo-adalimumab and an unrestricted grant for independent GCP monitoring, data management, and statistical analysis, and Meda Pharmaceuticals supplied triamcinolone hexacetonide. AbbVie and Meda were not involved in the study set-up, data collection, analysis, or interpretation, and had no influence on the publication of data.

Disclosure statement

Merete Lund Hetland has received research grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis. She chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. She also co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. Lykke Midtbøll Ørnbjerg has received a research grant from Novartis. Norma Biln is an employee of Augurex, Vancouver, Canada. Mikkel Østergaard has received research grants from Abbvie, BMS, Merck, Celgene and Novartis, and speaker and/or consultancy fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/03009742.2022.2087900.