Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice

Abstract

Objective: Evaluate the association between the multi-biomarker disease activity (MBDA) score and radiographic progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF)-α inhibitors.

Methods: Change (Δ) in modified total Sharp score (mTSS) over 52 weeks and disease activity scores were examined retrospectively by Spearman's rank correlation coefficient in patients (N = 83) with RA initiating TNF-inhibitor treatment. Relative risk (RR) of ΔmTSS >0.5 for low MBDA score and 28-joint count disease activity score (DAS28) categories and associations between ΔmTSS and MBDA score categories conditional on DAS28 categories were assessed.

Results: At 52 weeks, 34% of patients had ΔmTSS >0.5 and 12% had ΔmTSS >3. Strongest correlations were observed between ΔmTSS and MBDA score (r = 0.47) or DAS28 (r = 0.42) at Week 24 and for area under the curve at Week 52 (MBDA score: r = 0.44, DAS28: r = 0.41), all p < 0.001. At Week 24, RR of ΔmTSS >0.5 for moderate/high MBDA score (≥30) or DAS28 (>3.2) were 6.6 (p < 0.001) and 2.7 (p = 0.005), respectively. Low DAS28 had greater risk of ΔmTSS >0.5 at 52 weeks when MBDA score was ≥30 (p < 0.05).

Conclusion: Higher MBDA score or DAS28 at Week 24 was associated with greater radiographic progression over 52 weeks of TNF-inhibitor treatment. MBDA score improved risk discrimination for radiographic progression within DAS28 categories.

Keywords:

• Biomarkers
• MBDA score
• Radiographic progression
• Rheumatoid arthritis
• TNF inhibitor

Acknowledgments

The authors thank the medical staff of all participating institutions for providing data, and the laboratory staff at Crescendo Bioscience Inc. for conducting the multi-biomarker disease activity tests. We thank Sara Arzeno and Arbor Communications who provided medical writing assistance, and Eric H. Sasso, MD, Oscar G. Segurado, MD, PhD, and Rebecca Bolce, for constructive discussions, and critical review and editing of this manuscript.

S.H. and Y.T. conceived the study. S.H., W.L., N.D., and Y.T. participated in its design and coordination. S.H., S.K., S.F., Y.M., K.H., N.S., K.Y., K.S., and Y.T. enrolled and managed the patients in clinic. S.H., S.K., S.F., and Y.M. participated in radiographic evaluation. Laboratory staff at Crescendo Bioscience Inc. performed measurement of the MBDA score. S.H., W.L., N.D., and Y.T. performed the statistical analyses, data interpretation and wrote the manuscript. S.A. provided medical writing assistance and editorial review. O.S., R.B., and E.S. contributed to data intepretation and review draft manuscript. All authors read and approved the final manuscript.

Conflict of interest

S.H. has received speaking fees from AbbVie, Eisai, and Bristol-Myers Squibb. W.L. and N.D. are employees of Crescendo Bioscience Inc. Y.K. has received consulting fees and/or honoraria from Pfizer Japan Inc. Y.T. has received consulting fees, speaking fees, and/or honoraria from AbbVie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen and has received research grants from Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, AbbVie, Bristol-Myers. S.K., S.F., Y.M., K.H., N.S., and K.S. report no conflicts of interest. This work was supported in part by Crescendo Bioscience, who provided biomarker analyses and statistical support. The study was also supported in part by a Research Grant-In-Aid for Scientific Research by the Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the University of Occupational and Environmental Health, Japan.

Supplementary material available online