Background Autoantibodies are a hallmark of RA. Since many years ACPA are regarded as more specific than RF for diagnostic and prognostic utility. These data are not unequivocal and most of them have come from observational studies. While it is known for long that RF+ patients have more active and severe disease than RF-, it is not clear if this is due to RF, ACPA or both in the light of the large (>80%) overlap of RF and ACPA and the above controversy.
Objectives To compare the extent of disease activity in RF+ and/or ACPA+ patients to understand the impact of these autoantibodies on disease activity of RA.
Methods We were kindly provided patient level data from a multicenter randomized controlled trial comparing methotrexate (MTX) and rituximab plus MTX in early (<4 years) RA, MTX-naïve and with a predefined active disease (≥8 swollen and tender joints) and RF+ or erosive disease at entry (IMAGE trial)1. Core set variables and levels of RF (by nephelometry) and ACPA (by ELISA) were available. For the purpose of this analysis, we focused on baseline data and pooled the patients of all 3 treatment groups. Following subgroups were formed: RF-/ACPA- (n=64); RF+/ACPA+ (n=611); RF+/ACPA- (n=40); RF-/ACPA+ (n=29). We compared disease activity variables and indices (disease activity score, DAS28; simplified and clinical disease activity index, SDAI, CDAI) across these groups using Kruskal Wallis test for overall assessment, and Wilcoxon test for subsequent pairwise comparisons. A focus of the latter was comparing the RF+/ACPA- and RF-/ACPA+ populations.
Results At baseline, DAS28 was 6.9, 7.1, 7.1 and 6.6, respectively, and SDAI 47.8, 49.8, 53.1, 42.3, and significantly different among the groups. By both scores, the lowest values were seen for the RF-/ACPA+ population, significantly lower than in the RF+/ACPA- group (p=0.014 for DAS28, and p=0.004 for SDAI). Similar data were seen for CDAI, swollen and tender joint counts, while for ESR and CRP there was a similar numerical trend(Table). Interestingly, RF+/ACPA+ patients tended to have slightly lower activity than RF+/ACPA-, and higher than RF-/ACPA+. Importantly, similar findings were made for the baseline values of each of the trial arms when assessed individually (not shown).
Conclusions The data suggest that RF may contribute more strongly to disease activity than ACPA. While they can only be hypothesis generating, confirmation in other trial databases could shed new light on the prognostic value of ACPA compared to RF.
Acknowledgment. We thank Roche for kindly providing the data for this study.
Tak, P.P. et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis 70, 39-46 (2011).
Disclosure of Interest J. Smolen Grant/Research support from: Roche, Consultant for: Roche, F. Alasti: None Declared, D. Aletaha Consultant for: Roche
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