New Biomarker May Predict DAS-Remission During Tocilizumab Therapy in RA

tube of blood
tube of blood
In patients with rheumatoid arthritis, serum levels of reactive oxygen metabolites during treatment with tocilizumab are indicative of future clinical remission.

The reactive oxygen metabolites (ROM) serum level at 12 weeks during tocilizumab (TCZ) therapy may be a useful biomarker in the prediction of disease activity score (DAS)-remission at 52 weeks in rheumatoid arthritis (RA), according to study results published in BMC Rheumatology.

Researchers of several clinical studies have revealed that TCZ is highly effective in the treatment of RA; however, clinicians have a difficult time predicting future response during TCZ therapy and need a novel biomarker to predict future clinical remission. Recently, researchers found that the ROM value in RA at 12 weeks after treatment with biologic agents may be a predictor of 52-week remission. The objective of this study’s researchers was to determine whether ROM may be useful at predicting future clinical remission during TCZ therapy.

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In this study, researchers evaluated 46 patients with RA who were receiving TCZ therapy. Patients were stratified into remission (n=36) and nonremission groups (n=10) based on DAS 28-erythrocyte sedimentation rate (ESR) or clinical disease activity index (CDAI) at 52 weeks. Researchers investigated the associations between ROM serum levels, C-reactive protein (CRP) levels, and matrix metalloproteinase-3 (MMP-3) levels at 4 and 12 weeks, along with remission as measured by DAS 28-ESR and CDAI at 52 weeks. Blood samples and measurements of DAS 28-ESR and CDAI were all collected during the same visit.

Researchers revealed that at 12 weeks, there were no significant differences in CRP and MMP-3 between the DAS- or CDAI-remission and nonremission groups; however, ROM values in the DAS-remission group were significantly lower than those in the nonremission group (278±62.4 vs 348±98.4, respectively, P <.01). There was no significant difference in ROM observed between the CDAI-remission and nonremission groups. 

For ROM, the area under the curve of the receiver operating characteristic curve was 0.735 and the cutoff value that distinguished DAS-remission from nonremission was 305.5 U. Carr (sensitivity 70.0%; specificity 72.2%). For CRP and MMP-3, the area under the curve was 0.688 and 0.436, respectively, and the DAS-ESR at 52 weeks was highly correlated with ROM at 12 weeks (r=0.597, P <.01). At 12 weeks, ROM was associated with DAS-remission at 52 weeks (odds ratio 6.067, 95% CI; 1.305-28.203), though CRP was not.

There were 2 main limitations of this study. First, the sample size was small, as a larger sample size may be needed to confirm whether ROM is predictive of remission in RA. Second, the role of oxidative stress in the pathobiology of RA remains unclear, and future studies are needed to establish its clinical significance in RA.

The study researchers concluded that ROM is a superior biomarker to CRP and MMP-3 in the prediction of DAS-remission in RA and that ROM serum levels at 12 weeks during TCZ treatment are useful in the prediction of DAS-remission at 52 weeks in this population. 


Nakajima A, Terayama K, Sonobe M, et al. Serum levels of reactive oxygen metabolites at 12 weeks during tocilizumab therapy are predictive of 52 weeks-disease activity score-remission in patients with rheumatoid arthritis [published online December 16, 2019]. BMC Rheumatol. doi: 10.1186/s41927-019-0096-1