Proteomic analysis to define predictors of treatment response to adalimumab or methotrexate in rheumatoid arthritis patients

Stephanie F Ling,Petra Budde,Peter Schulz-Knappe,Hans-Dieter Zucht,Anne Barton,Nisha Nair,Suzanne M M Verstappen,Darren Plant

doi:10.1038/s41397-019-0139-4

Abstract

Seropositivity for anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA), a chronic autoimmune arthritis, is associated with worse long-term disease outcomes. ACPA is ubiquitously tested in RA patients, but other autoantibodies exist (in both citrullinated and non-citrullinated form) which may provide additional information on RA subtypes and/or treatment response. We used a multiplex bead-based assay of 376 autoantibodies to test associations between these autoantibodies and treatment response in RA patients. Clusters of patients with similar autoantibody expression were defined and cluster membership was associated with treatment response. Thirty-four autoantibodies were differentially expressed in RA patients compared with healthy controls; citrullinated vimentin was associated with treatment response. A selection of citrullinated autoantibodies was found to be associated with treatment response in a subanalysis of ACPA-negative RA patients. Finer ACPA specificities in ACPA-negative RA patients may be predictive of treatment response and could represent a rich vein of future study.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that can have multisystem involvement
anti-citrullinated peptide antibodies (ACPA) alone was the best predictor of DAS28 improvement in a model adjusted for age, gender, disease duration and baseline DAS28
A model using ACPA as measured using the CCP2 assay as the independent variable was significantly associated with good European League Against Rheumatism (EULAR) response (ORadj 2.40, 95% CI 1.24–4.77, p = 0.010), with improved model fit compared with the multivariate autoantibody model (AIC 224.07, vs Akaike information criterion (AIC) 267.63 in multivariate autoantibody model)

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that can have multisystem involvement. Associations between cluster membership and treatment outcomes at 3/6 months were analysed using: (i) linear regression for improvement in DAS28, with a negative value indicating an increased score i.e. worsening disease activity; (ii) logistic regression for good vs moderate/poor and poor vs moderate/good EULAR response.

Results

Conclusion