Background/Purpose:

A multi-biomarker disease activity (MBDA) score has been validated as a measure of disease activity in rheumatoid arthritis. This study aimed to see if baseline MBDA score and early treatment-induced changes in MDBA score predict magnetic resonance imaging (MRI) inflammation and joint damage at week 26 and 52 in patients initiating anti-TNF therapy in an investigator-initiated trial (HURRAH trial, NCT00696059).

Methods:

Fifty-two RA patients with active disease despite conventional DMARD therapy were included. All started adalimumab 40 mg s.c. eow at baseline and continued on methotrexate. MRI of the wrist and MCP joints of one hand was obtained at baseline, week 26 and 52, and OMERACT RAMRIS scores were assigned. Blood tests were drawn at baseline, week 2, 6, 12, 26, 39 and 52 for measurement of 12 serum biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, leptin, resistin, SAA, CRP) used to generate a Vectra^® DA algorithm score. Associations between MBDA score, DAS28-CRP and changes in MRI inflammation and joint damage at week 26 and 52 were tested using Spearman’s rank correlations. We did not control for multiple testing in this post-hoc analysis.

Results:

Of the 52 patients, 67% were women, 79% IgM rheumatoid factor positive. At baseline, age was median 61 years (range 19-86), disease duration 7 years (0-36), DAS28-CRP 4.9 (2.9-7.4), HAQ 1.125 (0-2.125), MRI synovitis score 15 (3-21), MRI bone marrow oedema score 7 (0-42), MRI erosion score 16 (3-155), MBDA score 63 (15-89).

At week 26 MBDA score was statistically significantly correlated with MRI synovitis (rho = 0.42, p=0.016), but not with MRI bone marrow edema (rho = 0.32, p=0.06). At baseline and week 52 no statistically significant correlations between MBDA score and MRI inflammation were found.

MBDA score at week 2 and 6 and percent change in MBDA score at week 6 predicted changes in MRI synovitis score at week 26. In similar analyses at week 52, no statistically significant associations were found. A borderline significant (p = 0.07) correlation was observed between percent change in MBDA score at week 6 and change in MRI erosion score at week 26.

In all 15 patients with clinical remission (DAS28-CRP<2.6), subclinical inflammation could be detected at 6 months by MRI (all had synovitis, 9 had bone marrow edema). Of these 15 patients only 2 (13%) were grouped as in MBDA remission (≤25), 7 (44%) in MBDA moderate disease activity (30-44) and 6 (40%) in MBDA high disease activity (>44). 4 patients had MRI erosive progression above the smallest detectable difference (change in score ≥3) at week 52, none of these were in clinical or MBDA remission at week 26.

	Change in MRI synovits score from baseline to week 26				Change in MRI bone marrow edema score from baseline to week 26				Change in MRI erosion score from baseline to week 26
	N	rho	P-value		N	rho	P-value		N	rho	P-value
Baseline MBDA	36	0.28	0.10		36	0.06	0.73		38	0.08	0.62
MDBA at week 6	34	0.49	0.033		34	0.10	0.58		36	0.28	0.10
Change in MBDA score at week 6	34	0.30	0.09		34	0.15	0.41		36	0.23	0.17
Percent change in MBDA score at week 6	34	0.44	0.009		34	0.15	0.41		36	0.31	0.06
Baseline DAS28-CRP	36	0.37	0.025		36	0.17	0.31		38	-0.00	0.99
DAS28-CRP at week 6	33	0.15	0.40		34	0.32	0.06		35	0.02	0.91
Change in DAS28-CRP score at week 6	33	-0.10	0.59		34	0.19	0.28		35	0.09	0.61
Percent change in DAS28-CRP score at week 6	33	-0.06	0.73		34	0.28	0.10		35	0.11	0.54

Conclusion:

MDBA score at week 2 and 6 and percent change in MBDA score at week 6 was predictive of MRI synovitis at week 26, but not at week 52. This study encourages further investigation of MBDA as en early marker of treatment response and risk of erosive progression in patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-changes-in-a-multi-biomarker-disease-activity-score-after-starting-adalimumab-treatment-predict-change-in-mri-inflammation-at-6-months/