Prediction of therapeutic responses with ultrasonography in RA patients treated with an anti-TNF drug: a retrospective cohort study

Figures & data

Table 1. Bilateral synovial intra-articular recesses and periarticular sites evaluated by ultrasound in bilateral joints.

MCP (1–5), PIP (1–5)	Dorsal recess
Wrist	Radiocarpal recesses
	Ulnarcarpal recesses
	Intercarpal recesses
Elbow	Humeroradial joint
	Humeroulnar joint
	Posterior recesses
Shoulder	Subdeltoid bursa
	Biceps sheath
	Subacromial bursa
Knee	Suprapatellar recesses
	Medial parapatellar recess
	Lateral parapatellar recess
	Medial femorotibial joint line
	Lateral femorotibial joint line

The data provide the details of the ultrasound (US) examination for synovial hypertrophy and vascularization by gray-scale imaging and PD assessed at 48 sites in 28 joints. MCP: metacarpophalangeal joint; PD: power Doppler; PIP: proximal interphalangeal joint.

Table 2. The 86 RA patients’ baseline clinical and laboratory data, and treatment information.

Age, years	54.8 (15.6)
Female	76.9%
Disease duration, years [IQR]	6.9 [1–9.7]
RF-positive	68.6%
RF titer, IU mL^−1 [IQR]	40.2 [2–104.5]
ACPA-positive	77.9%
ACPA titer, U mL^−1 [IQR]	141.8 [1.4–151.5]
CRP, mg dL^−1 [IQR]	1.4 [0.3–2.9]
ESR, mm hr^−1 [IQR]	33.1 [12–52]
MMP-3, ng mL^−1 [IQR]	266.8 [88.5–331.1]
Tender joints, range 0–28 [IQR]	6.4 [2–8]
Swollen joints, range 0–28 [IQR]	5.4 [1.5–9]
Pt-VAS, 0–100 mm	55.3 (25.9)
DAS28-CRP score	4.3 (1.3)
HAQDI, range 0–3	1.2 (0.8)
PSL, mg day^−1 [IQR]	46.5%, 3.7 [0–6.3]
MTX, mg week^−1	80%, 5.7 (3.7)
Anti-TNF drug:
Etanercept	28.6%
Adalimumab	24.8%
Infliximab	20.9%
Certolizumab pegol	18.7%
Golimumab	7%

Values are median [25th–75th centiles] or mean (SD), unless otherwise indicated. ACPA: anticitrullinated peptide antibody; CRP: C-reactive protein; DAS: disease activity score; ESR: erythrocyte sedimentation rate; HAQDI: Health Assessment Questionnaire Disability Index; IQR: interquartile range; MMP-3: matrix metalloproteinase-3; PSL: prednisolone; MTX: methotrexate; Pt-VAS: patient visual analogue scale; RF: rheumatoid factor; SJC: swollen joint count; TJC: tender joint count; TNF: tumor necrosis factor.

Figure 1. Comparisons of clinical disease activity and US indexes between baseline and 54 weeks in RA patients treated with an anti-TNF agent. At 54 weeks, the patients' swollen joint count (SJC), tender joint count (TJC), patient visual analogue scale (ptVAS), and the mean DAS28-CRP as clinical parameters were significantly decreased compared to their baseline values. As US parameters, the synovial hypertrophy index (SHI) and Doppler synovitis index (DSI) at 54 weeks were significantly decreased compared to baseline. Values are median [25th–75th centiles] or mean (SD), unless otherwise indicated. *p < .05, **p < .005, ***p < .0005, ****p < .0001 for the numerical values at baseline versus 54 weeks by Mann-Whitney U-test.

Figure 2. Correlations between clinical disease activity and US indexes, and the ROC curves of US findings for predicting remission. The relationship of DAS28-CRP and US findings at baseline and 54 weeks. (A,B) The SHI showed a significant correlation with the DAS28-CRP score at baseline and 54 weeks. (C) A weak correlation of the DSI was found with the DAS28-CRP score at baseline. (D) There was no correlation of the DSI with the DAS28-CRP score at 54 weeks. (E) The SHI (i.e., ≤34) and DSI (i.e., ≤7) cut-off point at baseline provided the highest sensitivity and specificity for remission at 54 weeks (SHI; 86.3% and 71.5%, DSI; 77.2% and 48.8%, respectively). **p < .005, ****p < .0001 for the SHI and DSI versus DAS28-CRP by Spearman’s correlation.

Table 3. Predictors of remission at baseline.

	No-remission	Remission	p-value
No. of patients, %	42, 48.8	44, 51.2	.77
Age, years	59.1 (14)	51.8 (16.4)	.07
Female	82.1%	70%	.36
Disease duration, years [IQR]	2.5 [0.5–8]	3.5 [1.8–7.6]	.76
RF-positive	78.9%	76.7%	.86
RF titer, IU mL^−1 [IQR]	41 [17–101]	33 [0–134]	.29
ACPA	72.1%	79.1%	.77
ACPA titer, IU mL^−1 [IQR]	66.3 [4.9–254.1]	19[0–277.3]	.99
CRP, mg dL^−1 [IQR]	1 [0.4–3.3]	0.7[0.3–1.7]	.18
ESR, mm hr^−1 [IQR]	33.5 [14.8–51]	19 [11.5–47.3]	.43
MMP–3, ng mL^−1 [IQR]	175 [82.9–334.8]	137.1 [72.1–314]	.85
TJC, range 0–28 [IQR]	5.5 [3–8.8]	3.5 [1–6]	.24
SJC, range 0–28 [IQR]	4.5 [2–9]	3 [0.75–6.3]	.19
Pt–VAS, 0–100 mm [IQR]	53 [40–77.5]	50 [29.8–70]	.42
DAS28-CRP score	4.4 (1.1)	3.9 (1.3)	.12
HAQDI, range 0–3	1.3 (0.2)	0.8 (0.2)	<.05*
PSL, %, mg day^−1 [IQR]	44.4, 3.3 [0–5.8]	42.9, 3.2 [0–5]	1, .97
MTX, %, mg week^−1	85.7, 5.8 (3.2)	76.7, 5.8 (3.9)	.51, .99
US findings
SHI, range 0–144	41 [22–49.5]	32 [15.5–35.3]	<.005**
DSI, range 0–144	6 [1–15]	1 [0–7]	<.05*

Values are median [25th–75th centiles] or mean (SD), unless otherwise indicated. *p < .05, **p < .005 for the numerical values at baseline in no-remission versus remission at 54 weeks by Mann-Whitney and chi-square test. Abbreviations are explained in the Table 2 footnote.

Table 4. Association between remission at 54 weeks and US findings at baseline.

	OR	95% CI
DAS28-CRP <2.7	3.1	1.5–11.2
Female	2.2	0.7–4.1
RF-positive	1.8	0.7–8.2
ACPA-positive	1.4	0.8–6.1
RF- and ACPA-positive	1.6	0.8–6.3
SHI cut-off score 34	6.7	1.9–27.4
DSI cut-off score 7	3.1	0.9–12.3

The cut-off values were calculated by a receiving operating curves analysis. ACPA: anticitrullinated peptide antibody; DAS28-CRP: DAS28-C-reactive protein; DSI: Doppler synovitis index; RF: rheumatoid factor; SHI: synovial hypertrophy index.