Background/Purpose: Tumor necrosis factor-α inhibitors (TNFi) are highly effective in patients with rheumatoid arthritis (RA), while not effective in all, with predictors of response being necessary. Although genetic, inflammatory and serologic biomarkers are under major investigation for this purpose, little is known about the predictive value of ultrasonographic parameters in RA. We aimed to investigate the ability of ultrasonographic parameters to predict which patients with RA will benefit from the treatment with TNFi in terms of EULAR response.
Methods : Biologic naive RA patients starting treatment with TNFi were examined longitudinally by ultrasonography (US) (both Gray–Scale [GS] and Power Doppler [PD]) of 28 joints according to standard scans of EULAR guideline and clinically (tender/swollen joint counts, DAS28 and HAQ scores) at baseline and after 3 and 6 months. US examinations were performed by an experienced sonographer (NI) using a MyLab 70 US machine (Esaote, Italy) equipped with 6-18 and 4-13 MHz broad band multi–frequency linear transducer. US synovitis GS and PD signals were semiquantitatively graded from 0 to 3. Total PD and GS synovitis scores of all sites are recorded as sum scores of PD and GS, respectively. The clinical response was evaluated according to the EULAR response criteria at 3rd month. Potential ultrasonographic predictors of response were identified using multivariate binary logistic regression models.
Results : The study cohort consisted of 42 RA patients (F/M=33/9, mean age 49.0±10.7 years) with a mean disease duration of 9.1±7.5 years and mean baseline DAS28 score of 5.5±1.0. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (CCP) positivity were 76.2% and 64.3%, respectively. Baseline characteristics of TNFi responders (30/42) and non–responders (12/42) are shown in Table 1. Swollen joint count (p= 0.05), sum scores of baseline PD (p= 0.048), GS (p= 0.048) and PD+GS (p= 0.046) differed significantly between responders and non–responders. Baseline PD sum score was the only ultrasonographic parameter in the multivariate analysis predicting which patients achieve good/moderate EULAR response with TNFi at 3rd month (p= 0.004). The mean PD+GS, PD and GS sum scores decreased significantly from baseline to 3 months (p<0.001 for all parameters) whereas decrease between 3rd and 6th months was nonsignificant for all US parameters (p=0.128, p=0.266, p= 0.105, respectively).
Conclusion : Our data underline that baseline PD scores, despite similar clinical features, can predict which patients will respond to TNFi therapy. Ultrasonographic response to TNFi treatment can be achieved substantially in the first 3 months. Beyond 3rd month changes in US scores are mostly nonsignificant.
Table 1. Baseline characteristics of TNFi responders and nonresponders
Responders (n=30)
|
Non–responders (n=12)
|
p Value
|
|
Age (years)
|
48.8±10.6
|
49.6±11.5
|
0.81 |
Disease duration (years)
|
8.0±7.2
|
11.9±7.8
|
0.13 |
Treatment delay (months)
|
32.2±51.0
|
35.2±38.2
|
0.85 |
RF titer (IU/mL)
|
166.4±233.9
|
295.1±586.8
|
0.31 |
Anti- CCP titer (U/mL)
|
78.7±147.0
|
232.2±457.5
|
0.10 |
DAS28
|
5.5±0.9
|
5.5±1.3
|
0.99 |
Pain VAS (0-100 mm)
|
66.0±21.7
|
79.2±16.7
|
0.067 |
ESR (mm/h)
|
43.7±20.7
|
40.0±22.5
|
0.61 |
CRP (mg/L)
|
27.2±34.1
|
28.6±28.4
|
0.90 |
Tender joint count (0-28)
|
8.0±6.8
|
12.0±9.5
|
0.12 |
Swollen joint count (0-28)
|
5.7±5.0
|
9.8±7.8
|
0.05 |
HAQ score
|
1.1±0.6
|
1.3±0.4
|
0.22 |
Prednisolone dose, mg/day
|
5.7±3.1
|
5.8±2.2
|
0.93 |
Sum score of PD (0-84)
|
12.5±9.8
|
20.1±13.2
|
0.048 |
Sum score of GS (0-84)
|
16.1±11.7
|
25.7±15.6
|
0.048 |
Sum score of PD+GS (0-168)
|
29.0±21.4
|
45.6±28.5
|
0.046 |
The values were presented as mean±SD
Disclosure:
N. Inanc,
None;
G. Ozen,
None;
H. Direskeneli,
None.
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