Background While MTX is most successfully used, some patients treated succeedingly with MTX-alone suffer from radiographic progression. Since PREMIER and OPTIMA studies show that combination with MTX+adalimumab (ADA) effectively halts radiographic progression as compared to MTX-alone, it is critical to identify the subgroup of patients potentially progressive with the treatment with MTX-alone beforehand whose radiographic progression can be halted by biologics.
Objectives To identify clinicalrelevant radiographic progressor (CRRP) or rapid radiographic progressor (RRP) among the patients succeedingly treated with MTX- alone.
Methods Clinical, structural and functional outcomes of RA patients who were succeedingly treated with MTX-alone (n=143) or those required additional ADA 40mg every other week (N=81) were evaluated using DAS28-4ESR, modified total Sharp score (mTSS) and a health assessment of questionnaire-disability index (HAQ-DI) for 3 years prospectively. Blood samples were tested for MMP-3 and anti-CCP antibody. To identify the predictor of CRRP (ΔTSS>3) or RRP (ΔTSS>5), variables at baseline were assessed in relation to joint destruction in an univariate logistic regression procedure.
Results The patients (mean: age 57.2 yrs, disease duration 6 yrs) were with high disease activity (mean: DAS28-ESR 5.5, CRP 2.7mg/dL) and joint destruction (mean TSS 35.8) on initiation of MTX or ADA plus MTX. Disease activity was significantly improved in either groups. However, as compared with MTX plus ADA group, DAS28 improvement and remission at 1 yr but not at 2 and 3 yrs were statistically inferior, and the structual remission rate was consistently inferior in the MTX-alone group. In the MTX-alone group, it was noted that the CRRP and RRP subgroup was with increased MMP-3 and higher anti-CCP antibody, whereas the clinical disease activity was similar between the groups. A logistic regression analysis showed that the MMP-3 level at baseline was significantly linked to CRRP and RRP after 1 yr of treatment in the MTX-alone group. The cut-off value of MMP-3 was calculated to be 103.7ng/ml by a logistic regression reciever operating charactristics (ROC) analysis. Among the MTX-alone group patients, those with less than 103.7ng/ml of MMP-3 did not belong to the CRRP and RRP subgroup, with the sensitivity of 80 % and 90% respectively.
Conclusions We identified basal MMP-3 level as a predictoridentifying the CRRP or RRP subgroup among rheumatoid patients who have been succeedingly treated with MTX-alone. We recommend a treatment option of adding biologics such as ADA to the MTX-treated patients with more than 103.7ng/ml of serum MMP-3 to prevent further radiographic progression.
Acknowledgements We thank Dr. Fusae Sawamura for valuable advices.
Disclosure of Interest None Declared
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