Background/Purpose Clinical remission is achievable for patients with early rheumatoid arthritis (ERA). Identification of predictors for response of treatment may provide risk estimation and help for the development of personalized medicine. On the other hand, patients with ERA die prematurely primarily because of cardiovascular disease. The aim of this study is to study the association between the baseline IL-33 and soluble ST2 (sST2) levels with disease remission and progression of carotid atherosclerosis in ERA patients.

Methods Ninety-eight ERA patients were enrolled. Disease activity and the presence of carotid plaque were evaluated at baseline and 12 months later. Plasma IL-33 and sST2 levels were determined using enzyme-linked immunosorbent assay kits.

Results Baseline IL-33 and sST2 levels were associated with inflammatory markers and cardiovascular (CV) risk factors. 44(45%), 18(18%) and 21(21%) patients achieved remission based on 28-joint disease activity score (DAS28), Boolean and simplified disease activity score (SDAI) criteria at 12 months. Patients with detectable IL-33 at baseline were less likely to achieve DAS28 (P=0.010) and SDAI remission (P=0.021), while a lower baseline sST2 level was able to predict DAS28, Boolean and SDAI remission (P=0.005, 0.001 and <0.001, respectively). By multivariate analysis, a lower baseline sST2 level independently predict Boolean (OR: 0.789, P=0.005) and SDAI remission (0.812, P=0.008). Regarding carotid atherosclerosis, 9/98(9.2%) patients with plaque progression were observed. Baseline IL-33 was detectable in 8/9(89%) and 42/83(51%) of patients with and without plaque progression (P=0.029). Baseline detectable IL-33 was an independent predictor for plaque progression after adjusting for traditional CV risk factors (27.523, P=0.017).

Conclusion Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA.

Table 1. Multivariable analysis for remission of disease and progression of carotid plaques

Events at month 12	Factors*	OR	95% CI	P value
DAS28 remission	Disease duration	2.371	1.050-5.353	0.038
(Event**: n=42, 47%)	ESR	0.970	0.953-0.988	0.001
	Prednisolone use during study	0.202	0.055-0.751	0.017
Boolean remission	sST2	0.789	0.669-0.932	0.005
(Event**: n=17, 18%)
SDAI remission	Pain	0.766	0.606-0.969	0.026
(Event**: n=19, 21%)	sST2	0.812	0.696-0.948	0.008
Plaque progression	Age	1.217	1.063-1.393	0.004
(Event**: n=9, 11%)	Detectable IL-33	27.523	1.805-419.6	0.017
* Variables were determined at baseline except where specifically indicated. ** Number/percentage of event in the multivariate analysis after cases with unavailable data excluded, may be different from total number/percentage in the text.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-33-and-soluble-st2-levels-as-novel-predictors-for-remission-and-progression-of-carotid-plaque-in-early-rheumatoid-arthritis-a-prospective-study/