Session Information
Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose: Cigarette smoking is a risk factor for RA and has been associated with increased disease severity and lower rates of disease remission. We examined whether smoking cessation might be associated with reduced disease activity and investigated the association of autoantibody levels with smoking status.
Methods: RA patients from the Veterans Affairs RA (VARA) registry were studied (n = 1468, 76.9% anti-CCP2+, 90.7% male, median age 63 [IQR 57-72], median disease duration 8.45 years [IQR 2.8-18]). Baseline serum samples were evaluated for levels of 19 distinct ACPA and 17 cytokines using the BioPlex platform. Baseline smoking status was recorded as current, former, or never. Cross-sectional associations of baseline smoking status with disease activity (DAS28) and its constituents as well as baseline levels of ACPA, and baseline levels of cytokines were assessed.
Results: Multiple measures of RA disease activity including DAS28 were significantly higher among current smokers compared with either former or never smokers (P<0.01), an effect limited to the seropositive (anti-CCP2 positive) population (Table 1). The number of inflammatory cytokines found in high concentration was significantly higher among current smokers compared with both former and non-smokers (FDR q-value <0.1%). Levels of both anti-CCP2 as well as ACPA subtypes were lower in never smokers but similar between current and former smokers while levels of RF were highest in current smokers, and lower in both former smokers and lowest in never smokers (Table 2).
Conclusion: Current smoking is strongly associated with increased RA disease activity as well as elevation in pro-inflammatory serum cytokines compared to both former and never smokers. Our findings suggest that continued tobacco exposure promotes greater RA disease activity, particularly in ACPA positive patients though independent of titer or specificity. The observation of reduced disease activity among former smokers, approaching that of never smokers, suggests that the effects of smoking may be reversed by smoking cessation. Whether RF may be a mediator of this effect remains to be clarified.
DAS28 |
Log(CRP) |
ACPA #Pos
|
ACPA Score |
Cytokine #Pos
|
Cytokine score |
CCP2 level |
RF level |
|
Current smoker
|
4.6 |
1.9 |
2.7 |
24.3 |
1.8 |
22.9 |
395.9 |
593.1 |
Former smoker
|
3.9 |
1.7 |
2.6 |
23.2 |
1.1 |
18.9 |
360.9 |
350.5 |
Never smoker
|
3.7 |
1.7 |
2.1 |
19.7 |
1.1 |
14.6 |
278.1 |
239.0 |
|
|
|
|
|
|
|
|
|
P-values*
|
|
|
|
|
|
|
|
|
Global ANOVA |
< 0.001 |
0.044 |
0.043 |
0.019 |
0.001 |
0.085 |
0.020 |
<0.001 |
Current vs. Never |
< 0.001 |
NS |
NS |
< 0.05 |
< 0.01 |
NS |
<0.05 |
<0.001 |
Current vs. Former |
< 0.001 |
NS |
NS |
NS |
< 0.01 |
NS |
NS |
<0.001 |
Former vs. Never |
NS |
NS |
NS |
NS |
NS |
NS |
NS |
NS |
Table 1: Measures of disease activity, ACPA, and cytokine expression among anti-CCP2 positive RA patients; *p-values among smoking groups generated using Scheffe’s method for multiple comparisons
|
Disclosure:
J. Sokolove,
None;
H. Sayles,
None;
C. Wagner,
None;
L. J. Lahey,
None;
G. M. Thiele,
None;
W. H. Robinson,
None;
A. Reimold,
None;
G. S. Kerr,
None;
G. W. Cannon,
AbbVie,
2;
T. R. Mikuls,
Genetech/Roche,
2.
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