Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: There is accumulating evidence that rheumatoid arthritis (RA) should be considered as prothrombotic state, explaining the increased risk of thromboembolic events. Suppressing inflammation could reduce this hypercoagulability. COBRA, the combination of step-down prednisolone, methotrexate and sulfasalazine (SSZ) is an effective antirheumatic therapy. However, glucocorticoids have been identified as risk factor for the development of thromboembolism. In this study we evaluated the course of haemostatic markers in RA patients during strong anti-inflammatory therapy and the dose-dependent effect of prednisolone on coagulation and fibrinolysis.
Methods: 22 patients diagnosed with early RA, were randomised to either COBRA therapy or an attenuated form (COBRA-light) with halved initial prednisolone dose and no SSZ. At baseline and after 1, 4 and 26 weeks of treatment, 10 ml of citrated blood was collected for measurement of prothrombin time (PT), activated partial thromboplastin time (aPTT) and five haemostatic markers: prothrombin fragment 1+2 (F1+2), factor VIII (FVIII), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1) and D-dimer. For statistical analyses t-tests and linear regression were used.
Results: Baseline characteristics were not significantly different between the 2 groups (each 11 patients). DAS44, CRP and ESR decreased significantly after 26 weeks (p<0.001). aPTT, D-dimer and F1+2 decreased during treatment in all patients (table). There was a significant positive association between decrease in CRP and BSE with D-dimer and decrease in CRP, BSE and DAS44 with F1+2 at all time points. There was no difference in the markers between the two groups, except for a stronger decrease in aPTT after 2 weeks (p=0.03) in the COBRA group. This difference was no longer seen at 4 weeks.
|
Table Change in haemostatic factors in all 22 RA patients |
||||
|
|
baseline |
2 weeks |
4 weeks |
26 weeks |
|
DAS44 |
3.9 (0.6) |
|
|
1.6 (0.9)** |
|
ESR (mm/h) |
25 (12-43) |
|
|
4 (3-7)** |
|
CRP (mg/L) |
13.0 (5.5-29.5) |
2.5 (2.5-2.7)** |
2.5 (2.5-4.5)** |
2.5 (2.5-2.7)** |
|
aPTT (sec) |
29.9 (28.5-34.9) |
26.2 (25.1-31.4)** |
26.8 (25.5-29.9)** |
27.9 (26.6-30.4)* |
|
PT (sec) |
11.2 (0.4) |
11.3 (0.5) |
11.1 (0.5) |
11.2 (0.5) |
|
FVIII (%) |
142 (105-179) |
151 (112-196)* |
152 (123-193) |
127 (111-170) |
|
D-dimer (FEU/L) |
1.18 (0.63-3.34) |
0.55 (0.29-1.26)** |
0.49 (0.26-0.84)** |
0.25 (0.21-0.78)** |
|
F1+2 (pmol/L |
342 (253-496) |
192 (146-305)* |
212 (160-285)** |
213 (153-319)* |
|
PAI-1 (ng/ml) |
35 (25-49) |
40 (19-63) |
24 (16-53) |
42 (17-73) |
|
vWF (%) |
115 (87-149) |
121 (86-157) |
138 (94-189)* |
101 (86-143) |
|
Values are mean (SD) or median (IQR) *p <0,05 and **p<0.001 change compared to baseline |
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Conclusion: Overall, both COBRA and COBRA-light therapy induced an improvement of inflammatory and procoagulant factors in RA. Prednisolone could have attenuated this effect, since the coagulation factors FVIII, vWF increased during the first weeks, when doses of prednisolone were highest. However, there were no remarkable differences in the haemostatic markers between the two groups, indicating that doses higher than 30 mg of prednisolone have no attributable effect on the procoagulant state in RA.
Disclosure:
I. A. M. van den Oever,
None;
D. J. F. Stuijver,
None;
D. den Uyl,
None;
B. van Zaane,
None;
M. M. ter Wee,
None;
W. F. Lems,
None;
D. van Schaardenburg,
None;
J. C. M. Meijers,
None;
V. E. A. Gerdes,
None;
M. T. Nurmohamed,
MBS, MSD, Roche, Abbott, Pfizer and UCB,
5,
MBS, MSD, Roche, Abbott, Pfizer and UCB,
8.
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