Improvement in clinical disease activity index when treatment selection is informed by the tumor necrosis factor-ɑ inhibitor molecular signature response classifier: analysis from the study to accelerate information of molecular signatures in rheumatoid arthritis

Figures & data

Table 1. Patient demographics and baseline characteristics.

Variable	Sub-categories	PNR-TNFi	PNR-altMOA	NPNR-TNFi	NPNR-altMOA	P-value (PNR-TNFi vs.PNR-altMOA)	P-value (NPNR-TNFi vs.NPNR-altMOA)
N		151	156	129	70
Age (year), mean (SD)		53.9 (13.7)	57.4 (12.6)	56.3 (14.0)	60.1 (12.5)	0.021	0.051
Female, n (%)		n = 135 (89)	n = 142 (91)	n = 89 (69)	n = 54 (77)	0.715	0.265
Duration of disease (years), median (IQR; n)		3.00 (Q1 = 0.50, Q3 = 8.75, IQR = 8.25, n = 150)	4.90 (Q1 = 2.00, Q3 = 10.50, IQR = 8.50, n = 155)	1.80 (Q1 = 0.50, Q3 = 6.90, IQR = 6.40, n = 129)	5.90 (Q1 = 2.20, Q3 = 16.65, IQR = 14.45, n = 70)	0.020	<0.001
Race, n (%)						0.463	0.657
	White	n = 118 (78)	n = 129 (83)	n = 107 (83)	n = 56 (8)	0.387	0.700
	Other	n = 20 (13)	n = 12 (8)	n = 7 (5)	n = 6 (9)	0.124	0.508
	Black or African American	n = 11 (7)	n = 10 (6)	n = 10 (8)	n = 5 (7)	0.816	1.000
	Asian	n = 1 (1)	n = 2 (1)	n = 4 (3)	n = 1 (1)	1.000	0.659
	American Indian or Alaskan Native	n = 1 (1)	n = 3 (2)	n = 1 (1)	n = 2 (3)	0.644	0.570
TNFi-naïve, n(%)		n = 115 (76)	n = 134 (86)	n = 95 (74)	n = 64 (91)	0.040	0.005
RF positive, n (%)		n = 51 (37)	n = 51 (38)	n = 55 (54)	n = 32 (58)	0.892	0.717
CCP positive, n (%)		n = 41 (27)	n = 42 (27)	n = 62 (48)	n = 38 (54)	1.000	0.457
CRP at baseline, mg/dl		10 (13.8)	9.5 (13.9)	11.9 (19.7)	10.7 (17.9)	0.725	0.665
HAQ at baseline, mean (SD)		0.8 (0.6)	0.8 (0.5)	0.5 (0.5)	0.7 (0.5)	0.824	0.089
Tender joints at baseline, mean (SD)		14.8 (9.1)	16.5 (9.4)	11.4 (8.2)	11.3 (8.2)	0.105	0.947
Swollen joints at baseline, mean (SD)		7.9 (6.7)	9 (6.8)	7.1 (6.5)	5.5 (5.8)	0.142	0.083
Methotrexate, n (%)		n = 83 (55)	n = 82 (53)	n = 76 (59)	n = 28 (4)	0.740	0.016
Prednisone, n (%)		n = 31 (21)	n = 44 (28)	n = 45 (35)	n = 22 (31)	0.139	0.632
Hydroxychloroquine, n (%)		n = 18 (12)	n = 11 (7)	n = 16 (12)	n = 9 (13)	0.173	1.000
TNFi, n (%)		n = 151 (100)		n = 129 (100)
	Etanercept	n = 20 (13)		n = 21 (16)
	Infliximab	n = 17 (11)		n = 11 (9)
	Golimumab	n = 40 (26)		n = 25 (19)
	Certolizumab	n = 21 (14)		n = 25 (19)
	Adalimumab	n = 53 (35)		n = 47 (36)
JAK, n (%)			n = 75 (48)		n = 35 (5)
	Upadacitinib		n = 45 (29)		n = 19 (27)
	Baricitinib		n = 5 (3)		n = 9 (13)
	Tofacitinib		n = 25 (16)		n = 7 (1)
T-cell, n (%)			n = 52 (34)		n = 22 (31)
	Abatacept		n = 52 (34)		n = 22 (31)
IL-6, n (%)			n = 22 (14)		n = 9 (13)
	Tocilizumab		n = 20 (13)		n = 8 (11)
	Sarilumab		n = 2 (1)		n = 1 (1)
B-cell, n (%)			6 (4)		4 (6)
	Rituximab		6 (4)		4 (6)

b/tsDMARD, biologic or targeted synthetic disease-modifying antirheumatic drug; SD, standard deviation; Q, quartile; IQR, interquartile range; TNFi, tumor necrosis factor-a inhibitor; JAK, Janus kinase inhibitor; IL-6, Interleukin- 6; PNR-TNFi, non-response to TNFi signal present therapy TNFi; PNR-altMOA, non-response to TNFi signal present, therapy alternative mechanisms of action to TNFi; NPNR-TNFi, non-response signal absent, therapy TNFi, NPNR- altMOA; non-response signal absent, therapy alternative mechanisms of action to TNFi

Figure 1. Study design and outcomes. a) Inclusion and exclusion criteria for patients included in the outcome analyses of this study. All patients were enrolled in the real-world AIMS study and in keeping with the inclusion criteria of the parent study were ≥18 years of age, had a clinical diagnosis of RA and MSRC test results. b) Mean change from baseline in absolute CDAI at 12- and 24-week follow-up visits for predicted non-responders to TNFi therapy who were treated with a TNFi (PNR-TNFi) or a b/tsDMARD with an alternative mechanism of action (PNR-altMOA).

Table 2. Mean change in CDAI scores from baseline to 12-week and 24-week follow-up visits in the AIMS cohort subsets.

Timepoint	Cohort	Endpoint (CDAI)	N	PNR-TNFi	PNR-altMOA
12 weeks	All	Absolute change	470	7.964	12.199
	Baseline High CDAI	Absolute change	313	10.13	13.994
	Baseline Moderate CDAI	Absolute change	157	2.168	4.507
24 weeks	All	Absolute change	274	7.757	14.192
	Baseline High CDAI	Absolute change	230	8.853	15.09
		% achieved lower than MDA		38.9%	55.7%
		% achieved lower than LDA		16.7%	22.8%
	Baseline Moderate CDAI	Absolute change	71	3.118	9.7
		% achieved lower than LDA		47.1%	71.4%

CDAI, clinical disease activity index; LDA, low disease activity according to CDAI scores; MDA, moderate disease activity according to CDAI scores; PNR-TNFi, non-response to TNFi signal present therapy TNFi; PNR-altMOA, non-response to TNFi signal present, therapy alternative mechanisms of action to TNFi