Multi-Biomarker Disease Activity (MBDA) Score and Prediction of Radiographic Progression in a Randomized Study of Patients with Early RA Treated with Methotrexate Alone or with Adalimumab

Cecilie Heegaard Brahe¹, Mikkel Østergaard², Julia Sidenius Johansen³, Nadine A. Defranoux⁴, Ching Chang Hwang⁵, Xingbin Wang⁴, Rebecca J. Bolce⁴, Eric H. Sasso⁴, Kim Hørslev-Petersen⁶, Kristian Stengaard-Pedersen⁷, Lykke Midtbøll Ørnbjerg⁸, Peter Junker⁹, Torkell Ellingsen¹⁰, Palle Ahlquist¹¹, Hanne Lindegaard¹², Asta Linauskas¹³, Annette Schlemmer¹⁴, Mette Yde Dam¹⁵, Ib Tønder Hansen¹⁶, Tine Lottenburger¹¹, Christian G. Ammitzbøll¹⁷, Anette Jørgensen¹⁷, Sophine B. Krintel⁸, Johnny Lillelund Raun¹⁸ and Merete Lund Hetland^3,19, ¹Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Glostrup, Denmark, ²Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Copenhagen, Denmark, ³Danish Rheumatologic Biobank and DANBIO registry, Rigshospitalet, Glostrup, Gentofte and Herlev University Hospital, Copenhagen, Denmark, ⁴Crescendo Bioscience Inc., South San Francisco, CA, ⁵Biostatistics, Crescendo Bioscience Inc., South San Francisco, CA, ⁶King Christian X Hospital for Rheumatic Diseases, Graasten, Denmark, ⁷Rigshospitalet (Glostrup and Blegdamsvej), Århus University Hospital, Odense University Hospital, Herlev/Gentofte Hospital, Slagelse Sygehus, Chr X hospital (University of South Denmark) and Zitelab Aps, DANBIO Registry and Departments of Rheumatology, Copenhagen, Denmark, ⁸Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, ⁹Department of Rheumatology C, Odense University Hospital, Odense, Denmark, ¹⁰Department of Rheumatology, Odense University Hospital, Odense, DK, Odense, Denmark, ¹¹Department of Medicine, Vejle Regional Hospital, Vejle, Denmark, ¹²The DANBIO registry and the Danish Departments of Rheumatology, Odense, Denmark, ¹³The DANBIO registry and the Danish Departments of Rheumatology, Copenhagen, Denmark, ¹⁴9Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark, ¹⁵Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark, ¹⁶Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, ¹⁷Department of Rheumatology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark, ¹⁸King Christian X Hospital for Rheumatic Diseases, South Jutland Hospital, Graasten, Denmark, ¹⁹Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark,, Copenhagen, Denmark

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Animal models, Biomarkers, Clinical research, radiography and rheumatoid arthritis

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Clinical Aspects - Poster III: Treatment – Monitoring, Outcomes, Adverse Events

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: The multi-biomarker disease activity (MBDA) score, which combines 12 serum biomarkers to measure RA disease activity on a scale of 1−100, has been found to be predictive of risk for radiographic progression.¹ The objectives of this study were to evaluate early RA patients from the randomized double-blinded OPERA trial for: 1) associations between baseline (BL) MBDA score and 12-month radiographic outcomes; 2) the value of adding MBDA score to anti-CCP for predicting radiographic progression.

Methods: In the OPERA trial, treatment-naive early RA patients (N=180) with moderate or high DAS28 were randomized to treatment with oral methotrexate and either adalimumab (ADA) (n=89) or placebo (n=91). Glucocorticoids were injected into up to 4 swollen joints per visit.² X-rays of hands and feet (n=164) from months 0 and 12 were assessed with the Sharp van der Heijde Total Sharp Score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (DTSS≥2). Anti-CCP status was dichotomized. MBDA score was determined at 0 and 3 months. Correlations between BL or change (D) MBDA score and radiographic progression were analyzed by Spearman´s rank correlation coefficient (r). Chi-Square test was used for comparisons. A logistic regression model, adjusted for BL demographics and disease activity measures, assessed association between MBDA score and radiographic progression.

Results: Patients had median (range) age 55 (19-86) years, disease duration 84 (42-214) days; 66% were female; 72% were positive for RF and 65% for anti-CCP. Median values at BL were DAS28-CRP 5.6 (3.3-8.6), MBDA score 59 (12-90) and TSS 2 (0-31). 42 patients had DTSS ≥ 2, median DTSS = 3 (2-22)/mean DTSS = 4.52 (3.84). BL MBDA score correlated with DTSS in the placebo (r=0.23, p=0.04) but not the ADA group (r=0.10, P=0.35). ΔMBDA score_0-3months was not correlated with DTSS. Patients with high BL MBDA score (>44) were more likely to progress radiographically (31%), while only 1/31 (3%) patients with MBDA score ≤44 progressed (p<0.01), and this was significant also for each treatment group. Moderate/high BL DAS28-CRP was not associated with radiographic progression (Figure 1A, B). BL MBDA score (OR=1.03 per unit increase [1.01-1.06]), and anti-CCP (OR=4.45 if positive [1.66-11.95]) were significantly associated with RP in multivariate analyses. 34% of anti-CCP positive and 12% of anti-CCP negative patients had RP (p<0.002). No anti-CCP+ patients with MBDA score ≤44 progressed radiographically, whereas stratifying by DAS28-CRP had no added value to anti-CCP alone (Figure 1C, D)

Conclusion: High BL MBDA score (>44) was a strong, independent predictor of radiographic progression and added value to anti-CCP status. Only 3% of patients with low or moderate BL MBDA score (≤44) progressed radiographically. (1) Hirata et al. Current Biomarker Findings 2015, 5:69-78 (2) Hørslev-Petersen K, et al., Ann Rheum Dis 2014; 73:654-661

Disclosure: C. H. Brahe, None; M. Østergaard, Abbott Immunology Pharmaceuticals, 2,Bristol-Myers Squibb, 2,Boehringer Ingelheim, 2,Eli Lilly and Company, 2,Merck Pharmaceuticals, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,UCB, 2,Celgene, 2,Sanofi-Aventis Pharmaceutical, 2,Regeneron, 2,Novartis Pharmaceutical Corporation, 2; J. S. Johansen, None; N. A. Defranoux, Crescendo Bioscience Inc., 1,Crescendo Bioscience Inc., 3; C. C. Hwang, Crescendo Bioscience Inc., 1,Crescendo Bioscience Inc., 3; X. Wang, Crescendo Bioscience Inc., 3; R. J. Bolce, Crescendo Bioscience Inc., 3; E. H. Sasso, Crescendo Bioscience, 9; K. Hørslev-Petersen, None; K. Stengaard-Pedersen, None; L. M. Ørnbjerg, None; P. Junker, None; T. Ellingsen, None; P. Ahlquist, None; H. Lindegaard, Novartis, Eli Lilly DK, Boehringer Ingelheim Danmark, MSD Denmark, 5; A. Linauskas, None; A. Schlemmer, None; M. Yde Dam, None; I. Tønder Hansen, None; T. Lottenburger, None; C. G. Ammitzbøll, None; A. Jørgensen, None; S. B. Krintel, None; J. L. Raun, None; M. Lund Hetland, AbbVie, BMS, MSD, Roche, Pfizer, UCB, Crescendo, 2.

To cite this abstract in AMA style:

Brahe CH, Østergaard M, Johansen JS, Defranoux NA, Hwang CC, Wang X, Bolce RJ, Sasso EH, Hørslev-Petersen K, Stengaard-Pedersen K, Ørnbjerg LM, Junker P, Ellingsen T, Ahlquist P, Lindegaard H, Linauskas A, Schlemmer A, Yde Dam M, Tønder Hansen I, Lottenburger T, Ammitzbøll CG, Jørgensen A, Krintel SB, Raun JL, Lund Hetland M. Multi-Biomarker Disease Activity (MBDA) Score and Prediction of Radiographic Progression in a Randomized Study of Patients with Early RA Treated with Methotrexate Alone or with Adalimumab [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/multi-biomarker-disease-activity-mbda-score-and-prediction-of-radiographic-progression-in-a-randomized-study-of-patients-with-early-ra-treated-with-methotrexate-alone-or-with-adalimumab/. Accessed .

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