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Abstract
Background/Purpose To evaluate biomarkers as predictors of impending erosion progression.
Methods Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations.
Results Out of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP).
Conclusions Adding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.
- Recent-onset inflammatory arthritis
- 14-3-3η
- Radiographic progression
- Anti-CCP2 antibodies
- Rheumatoid factor
- CRP
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Footnotes
Contributors GB contributed to the design of the study, patient recruitment, establishment of Sherbrooke database, data analysis and writing of the manuscript. AJBF, SR, PL and AM contributed to patient recruitment and follow-up, to study design and to writing of the manuscript. NC maintains the Sherbrooke database and participated in data analysis and writing of the manuscript. NB ensured the blinded measurement of 14-3-3η levels and contributed to writing of the manuscript. WPM helped design the study and contributed to data analysis and writing of the manuscript. All authors read and approved the final manuscript.
Funding This work was supported by the Canadian Institutes for Health Research MOP-110959. We also acknowledge previous support from The Arthritis Society Grants 00/201 and RG06/108. AJBF, PL, AM, SR and GB are part of the Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, which received a team grant from the Fonds de Recherche du Québec – Santé (FRQ-S). Since 2007, the Sherbrooke EUPA cohort has also received financial support from the Canadian ArTritis CoHort, a study designed and implemented by investigators and financially supported initially by Amgen Canada Inc. and Pfizer Canada Inc. via an unrestricted research grant. As of 2011, further support was provided by Hoffmann-La Roche Ltd, United Chemicals of Belgium Canada Inc., Bristol-Myers Squibb Canada Co., Abbott Laboratories Ltd and Janssen Biotech Inc. (a wholly owned subsidiary of Johnson and Johnson Inc.). The 14-3-3η measurements were performed free of charge by Augurex Life Sciences Inc, Augurex remaining totally blinded to clinical data. All the analyses were performed in Sherbrooke (by NC) without sharing of clinical data of individual patients with Augurex personnel or any other third party.
Competing interests Norma Biln is an Augurex Life Sciences Inc employee. None of the other authors reports any conflict of interest related to this manuscript, except that the 14-3-3η measurements were performed free of charge by Augurex Life Sciences Inc, Augurex remaining totally blinded to clinical data.
Patient consent for publication Not required.
Ethics approval The Ethics Review Board of the CHUS approved the EUPA study (registered at ClinicalTrials.gov ID: NCT00512239).
Data sharing statement Individual participant data that underlie the results reported in this article will be available after deidentification, beginning 9 months and ending 36 months after article publication, to researchers providing a methodologically sound research proposal. Study proposal, statistical analytic plan and analytic code will also be available to achieve aims in the approved proposal. Proposals should be sent to gilles.boire@usherbrooke.ca. To gain access, researchers will need to sign a data access agreement.
Provenance and peer review Not commissioned; externally peer reviewed.