Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: A multi-biomarker disease activity (MBDA) score has been developed for evaluation of disease activity of rheumatoid arthritis (RA) to complement clinical assessment and to provide information about underlying disease processes. We have reported the usefulness of MBDA as clinical measures of disease activity. However, relation of MBDA score with clinical features in RA patients treated with a JAK-inhibitor tofacitinib is unknown.
Methods: DAS28(ESR), SDAI, MBDA and modified total sharp score (mTSS) were evaluated at baseline and 1 year in 37 patients (31 women, mean age: 54.6 years, mean disease duration: 78.9 months) enrolled in phase II and III clinical trials of tofacitinib. Patients were randomized to different doses of tofacitinib or placebo for the first 3 to 6 months (8 patients with dosed tofacitinib as monotherapy and 29 patients with concomitant MTX). All patients were treated with tofacitinib 5 mg or 10 mg BID after 6 months. MBDA combines 12 serum biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, Leptin, Resistin, CRP, SAA) in a pre-specified algorithm resulting in a score between 1 and 100.
Results:
(1) Disease activity significantly improved: MBDA, 60.8 to 28.5 as well as SDAI 37.7 to 6.2, DAS28-ESR 6.4 to 3.0, HAQ-DI 1.4 to 0.8,. HAQ-DI ≤0.5 was achieved in 19 patients (51%). Yearly progression of mTSS (⊿mTSS) significantly decreased from 14.7 to 0.9 and 21 patients (56%) achieved structural remission.
(2) Significant correlation was observed between yearly ⊿MBDA score and⊿DAS28(ESR), ⊿SDAI or ⊿CDAI (p<0.01).
(3) When clinical remission was determined as MBDA ≤25, remission rate was similar among measurements. (SDAI 37.8%, DAS28-ESR 35.1%, MBDA 40.5%)
(4) No correlation was observed between ⊿mTSS and ⊿MBDA, ⊿DAS28(ESR), ⊿SDAI or ⊿CDAI.
(5) The proportion of radiographic progressors in remission was similar among different measurements. (38.5% (5/13) of DAS28-ESR remission, 35.7% (5/14) of SDAI remission and 33.3% (5/15) of MBDA remission)
(6) IL-6 decreased from 163.0pg/ml to 25.1pg/ml and MMP-3 decreased from 159.1ng/ml to 39.5ng/ml. The measures of IL-6 and MMP-3 at 52 weeks significantly correlated with change of mTSS (69.1 to 70.0).
(7) When patients were separated into 2 groups with median value of serum IL-6 (9.0ng/ml) at 52 weeks, 78% achieved structural remission in low concentration group, whereas 38% was achievable in high concentration group.
Conclusion: MBDA significantly correlated with cpnventional composite measures of disease activity and equally contributed to remission rate in patients with RA. Although ⊿MBDA did not correlate with ⊿mTSS in this study size, concentration of IL-6 and MMP-3 at 52 weeks correlated with change of mTSS. These results indicate that tofacitinib acts through the inhibition of IL-6 and is able to prevent bone destruction. Our results further support the usefulness of MBDA as an additional composite measure for RA disease activity.
Disclosure:
K. Yamaoka,
None;
S. Kubo,
None;
K. Sonomoto,
None;
S. Hirata,
None;
G. Cavet,
Crescendo Bioscience Inc.,
3;
R. Bolce,
Crescendo Bioscience Inc.,
3;
M. W. Rowe,
Cresendo bioscience inc,
3;
D. Chernoff,
Crescendo Bioscience Inc.,
3;
N. Defranoux,
Crescendo Bioscience Inc.,
3;
K. Saito,
None;
Y. Tanaka,
Bristol-Myers Squibb KK,
2,
MSD KK,
2,
Chugai Pharmaceutical ,
2,
Mitsubishi Tanabe Pharma,
2,
Astellas Pharma ,
2,
Abbot Japan ,
2,
Eisai,
2,
Janssen Pharmaceutical KK,
2,
Mitsubishi Tanabe Pharma ,
8,
Abbot Japan ,
8,
Chugai Pharmaceutical ,
8,
Janssen Pharmaceutica KK,
8,
Santen Pharmaceutical ,
8,
Pfizer Japan ,
8,
Astellas Pharma ,
8,
Daiichi Sankyo ,
8.
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