Correlation Between Treatment-to-target And Cyr61, IL-6,IL-17, Other Potential Determinants In Rheumatoid Arthritis:A Clinical Study

Background Rheumatoid arthritis(RA) is a chronic persistent autoimmune disease which characterized by inflammatory of the synovial membrane, mainly Symmetrically involving the hands, feet and other joints. RA is one of the major diseases that can result in patient disability. Treatment and disease control of RA patients have been attentioned widely. With the propose of " treat-to-target(T2T)" or “tight control” and the development of disease-modifying anti-rheumatic drugs, T2 T of RA have gradually been accepted and recognized widely. 2013 European League Against Rheumatism stressed that all RA patients should have reached clinical remission or low disease activity as the goal, that is " T2 T ".However, studies have found that the current rate of T2 T for RA patients is generally low, there is still a big gap between and reality and the ideal goal. therefore, potential determinants of T2 T rate in RA patients is crucial. Cysteine-rich protein 61, interleukin-6,interleukin-17 are found to be factors of promoting synovium proliferation, inflammation and tissue damage in RA patients. Cyr61, IL-6, IL-17 can amplifying inflammation, promote tissue injury, synovial hyperplasia and joint destruction in RA patients by acting on fibroblast-like synovial cells and other inflammatory cells to promote tumor necrosis factor-α, interleukin1, interleukin2, interleukin8, granulocyte-macrophage colony stimulating factor and other inflammatory cytokines. RA patients did not treated to target often have obvious synovitis, bone destruction and other system damage in clinical practice. Therefore, Cyr61, IL-6, IL-17 may be related to the treatment-to-target of RA patients compliance. Now there are rare reports about the relationship between Cyr61, IL-6, IL-17 and treatmengt-to-target of RA patients in our country.Objections To investigate T2 T rate of rheumatoid arthritis(RA), analyse its potential determinants. In addition, to analysis the relationship between Cyr61, IL-6, IL-17 and the development, T2 T of RA, in order to improve treatment-to-target rate of RAMethods Three hundred RA patients were collected from Augest 2012 to June 2013 in outpatient and inpatiet department of rheumatism, the First Affiliated Hospital of Medical University. All patients fulfilled the ACR diagnostic criteria in 1987/2010. Record the clinical and laboratory indexes of RA patients detailedly. Measure the levels of serum Cyr61、IL-6、IL-17 by enzyme-linked immunosorbent assay(ELISA).Results1. 300 RA patients were recruited, 36.7%(110 patients) of them had treated to target, 24.7%(74 patients) of them achived remission(DAS28≤2.6) and 12%(36 patients) achived low disease activity(DAS28≤3.2). 63.3%(190 patients) were not treated to target.2、All RA patients were treated with non-steroidal anti-inflammatory drugs(NSAIDS) or glucocorticoids or disease-modifying anti-rheumatic drugs(DMARDs). 181(60.3%) RA patients were treated regularly with DMARDs and 119(39.7%) patients were not. No differences were found about NSAIDS and glucocorticoids(mean dose:7.5mg) between T2 T group and non T2 T group. The T2 T rate of RA patients in regular treatment group and non regular treatment group were 48.6% and 18.5%(χ2 = 28.070, P <0.001).3. RA patients who were treated to target had younger age, higher education, fewer swollen joint counts( SJC),fewer tender joint counts(TJC), lower visual analogue scale(VAS), lower patient global assessment(Pt GA), lower physician global assessment(PGA), lower rheumatoid factor(RF), lower erythrocyte sedimentation rate(ESR), lower C-reactive protein(CRP) level, lower joint function classification, lower Health Assessment Questionnaire(HAQ) score, more regular treatment with disease-modifying anti-rheumatic drugs(≥3 months) and more treatmenet with MTX, HCQ, TGP, when compared with those were not.4. Comparison of serum Cyr61, IL-6, IL-17 among control group, T2 T group, non T2 T group: the serum level of IL-6, IL-17 among three groups were were significant different(P<0.001). IL-6, IL-17 level : RA group was higher than normal control group(P <0.05), non T2 T group was higher than T2 T group(P <0.05). There were no statistical difference regard to serum Cyr61 level among the different groups(P>0.05).5. Comparison of serum Cyr61, IL-6, IL-17 level between different sexes or ages: There were no statistical differences between different sexes or different ages(age> 50 years vs age≤50 years) and Cyr61,IL-6,IL-17(P>0.05).6. Comparison of serum Cyr61, IL-6, IL-17 among control group, established RA group, early RA group: difference of the serum level of IL-6, IL-17 among three groups were statistically significanct(P <0.001). Serum IL-6, IL-17 level : RA group was higher than normal control group(P <0.05). Whereas, no difference were found about IL-6,IL-17 between established RA group and early RA group(P>0.05). And there were still no statistical difference about serum Cyr61 level among the different groups(P>0.05).7. Comparison of serum Cyr61, IL-6, IL-17 among control group, RF negatitity group and RF positivity group: difference of the serum level of IL-6, IL-17 among three groups were statistically significanct(P <0.05). Serum level of IL-6,IL-17 in RF positivity group and serum level of Cyr61,IL-6 in RF negativity group were all higher than normal control group. Serum level of IL-17 in RF positivity group were higher than those in RF negatity group(P<0.05).8. Comparison of serum Cyr61, IL-6, IL-17 level among control group, anti-CCP negativity group, anti-CCP positivity group: the serum level of IL-6, IL-17 levels among three groups were significantly different(P <0.05), Serum level of IL-6,IL-17 in anti-CCP positivity group and serum level of Cyr61,IL-6 in anti-CCP negativity group were all higher than normal control group. Serum level of IL-17 in anti-CCP positivity group were higher than those in anti-CCP negativity group(P<0.05).9. Comparison of serum Cyr61, IL-6, IL-17 level among control group, bone erosion group, non bone erosion group: difference of difference of the serum level of IL-6, IL-17 among three groups were significanct statistically(P <0.05). The serum level of IL-6,IL-17 in bone erosion group and non bone erosion group were higher than those in normal control group. Serum level of Cyr61 in non bone erosion group was higher than those in normal control group. Whereas, there were no statistical difference about serum Cyr61,IL-6,IL-17 between bone erosion group and non bone erosion group(P>0.05).10. Ccorrelation between Cyr61, IL-6, IL-17 and clinical index: serum level of Cyr61 were significantly negative associated with RF, anti-CCP(P <0.005). Serum level of IL-6 were significantly positive associated with tender joint counts(TJC), swollen joint counts(SJC), visual analogue scale(VAS), patient global Assessment(Pt GA), physician global assessment(PGA), cyclic citrullinated peptides(CRP), erythrocyte sedimentation rate(ESR), disease activity score in 28 Joints(DAS28)(P <0.05); Serum level of IL-17 were significantly positive associated with with age, TJC, VAS, Pt GA, PGA, ESR, CRP, rheumatoid factor(RF), DAS28, and joint function classification positive correlation(P <0.05). Serum level of IL-6 were significantly positive associated with Serum level of IL-17 in RA patients(P<0.001), but there were no significant correlation between Cyr61 and IL-6, IL-17(P> 0.05).11. Regression analysis for potential determinants of treatment-to-target in RA patients: T2T of RA was considered as dependent variables, while age, VAS score, PGA, Health Assessment Questionnaire(HAQ), joint function classification, CRP, RF, regular treatment with disease-modifying anti-rheumatic drugs(DAMRDs), MTX, HCQ, TGP, IL-6, IL-17 were considered as independent variables. Logistic regression analyses were employed to identify factors independently associated with T2 T of RA. VAS score, CRP, RF, joint function classification, HCQ is independent factors influencing T2 T of RA.Conclusions1. Currenttly, T2 T rate is still low in RA patients. The T2 T rate in regular treatment group(48.6%)is higher than no regular treatment group(18.5%). Regular treatment with DMARDs plays an important role in the T2 T of RA.2. Age, VAS, PGA, HAQ, CRP, RF, joint function classification, MTX, HCQ, TGP may affect treatment-to-target of RA. VAS, CPR, RF, joint function classification and HCQ are independent factors for T2 T of RA.3. Serum IL-6, IL-17 levels are correlated with disease activity of RA patients. Serum Cyr61 level may corelate with RF/ CCP in RA, but it still need further study.