Background/Purpose:

In early rheumatoid arthritis (eRA), clinical and radiographic predictors would be very useful for optimizing available therapies. Individual biomarkers and their combinations, such as the multi-biomarker disease activity (MBDA, Vectra DA) test, can be considered for these purposes.  In the SWEFOT study, patients with eRA (symptom duration < 1 year) were started on methotrexate (MTX); at 3 months, responders (DAS28 < 3.2) continued MTX monotherapy and were followed in regular care, whereas non-responders were randomized into triple DMARD therapy or the addition of infliximab group. 

The objective of this study was to assess the 12 individual biomarkers that comprise the MBDA score at baseline (BL) as predictors of clinical response at 3 months and radiographic progression at 1 year in eRA.

Methods:

Analyses were performed for patients from the SWEFOT trial who had BL and 3-month data of DAS28 (based on ESR), the MBDA score (which has been validated to assess disease activity in RA patients) and the 12 individual biomarkers at BL; and for a subset of patients who also had radiographs at BL and 1 year (assessed using the Van der Heijde modified Sharp score [SHS]).  Patients with DAS28 > 3.2 at 3 months were considered clinical non-responders, and patients with a change in SHS > 0 as radiographic progressors (“radiological non-responders”). Group comparisons of biomarkers were performed by Mann-Whitney U test.

Results:

The results are summarized in the table below. Clinical non-responders had significantly higher BL values for CRP and IL-6 compared to responders. TNF-R1 and VCAM-1 were significantly lower for non-responders, while other biomarkers and the MBDA did not differ. The patients who progressed radiographically had, at BL, significantly higher MBDA scores, inflammatory biomarkers (CRP, SSA and IL-6), MMP-1, MMP-3 and TNF-R1, as well as a trend towards higher VEGF.

Biomarkers   at BL (mean±SEM)	clinical   responders (n=112)	clinical   non-responders (n=190)	P   value	Radiographic   non-progressors (n=116)	Radiographic   progressors (n=120)	P   value
CRP	45.8±6.22	65.5±5.42	0.048	48.2±6.39	73.35±6.84	<0.001
SAA	38.3±5.04	41.9±3.49	N.S.	33.9±4.31	48.6±4.73	0.004
IL-6	82.7±9.01	114.2±10.36	0.051	89.83±11.68	121.7±13.33	0.002
TNF-R1	2.05±0.06	1.8±0.04	0.002	1.85±0.05	2.01±0.06	0.047
MMP-1	12.1±0.94	13.9±0.71	N.S.	12.4±0.87	14.4±0.86	0.038
MMP-3	76.9±8.55	90.21±6.5	N.S.	73.4±8.26	97.64±8.21	0.010
YKL-40	103.5±9.93	106.9±6.44	N.S.	115.4±11.3	107.9±7.35	N.S.
Leptin	12.8±1.17	15.1±1.09	N.S.	16.3±1.81	13.32±1.13	N.S.
Resistin	7.23±0.26	7.31±0.21	N.S.	7.23±0.28	7.3±0.21	N.S.
EGF	196.05±12.1	187.9±8.29	N.S.	195.2±9.7	182.6±11.65	N.S.
VEGF	474±27.99	469.34±22.7	N.S.	437.4±27.24	511.2±29.12	0.069
VCAM-1	0.74±0.019	0.66±0.012	<0.001	0.67±0.016	0.72±0.018	N.S.
MBDA	57±1.3	59.6±1.14	N.S.	55.7±1.4	63.3±1.19	<0.001

Conclusion:

In eRA patients treated initially with MTX, some individual biomarkers at BL may help identify those patients who are less likely to achieve DAS28 < 3.2 after 3 months of MTX therapy.  Other biomarkers, as well as the MBDA score, may identify patients at higher risk for radiographic progression during the first year of therapy. These results suggest that biomarkers can differentially predict aspects of disease course in eRA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-early-rheumatoid-arthritis-the-12-individual-biomarkers-that-comprise-the-multiple-biomarker-disease-activity-score-relate-differentially-to-clinical-response-and-radiographic-progression-results/