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FRI0114 The effect of combination therapy and prednisolone on haemostatic markers in rheumatoid arthritis: The cobra-light study
  1. I.A. van den Oever1,
  2. D.J. Stuijver2,3,
  3. D. den Uyl4,
  4. B. van Zaane2,3,
  5. M.M. Terwee4,
  6. W.F. Lems4,
  7. J.C. Meijers2,
  8. V.E. Gerdes2,3,
  9. M.T. Nurmohamed1
  1. 1Rheumatology, Jan Van Breemen Research Institute | Reade
  2. 2Vascular Medicine, AMC
  3. 3Internal Medicine, Slotervaart Hospital
  4. 4Rheumatology, VUmc, Amsterdam, Netherlands


Background 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. Whether glucocorticoids induce a procoagulant state is controversial and depends on the population, thus the effect of prednisolone in RA is unknown.

Objectives To evaluate the course of haemostatic markers in RA patients during 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 without 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, ESR, 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 1. Change in haemostatic factors in all 22 RA patients

Conclusions Overall, both COBRA and COBRA-light therapy induced an improvement of inflammatory and procoagulant factors in RA. 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 of Interest None Declared

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