Influence of corticosteroids on C-reactive protein in patients with rheumatoid arthritis

Background

C-reactive protein (CRP) is an acute phase reactant. It is usually increased in rheumatoid arthritis (RA) patients when disease is most active. These patients would be expected to participate in clinical trials, high CRP being a frequent requirement for inclusion. At the same time this group of patients is usually treated with moderate to high dose steroids. Steroids have the potential to decrease CRP without modifying disease progression. It has been our clinical observation that very active patients are probably not influenced very much by steroids, but patients with moderate disease activity who use low doses of steroids have their CRP lowered or suppressed.

Hypothesis

Patients treated with low doses of corticosteroids would have a lower CRP than those treated with no steroids, precluding them from participating in clinical trials.

Methods

We studied the correlation between CRP and corticosteroid doses in RA patients, fulfilling the American Rheumatism Association 1987 criteria, treated with oral steroids, disease-modifying anti-rheumatic drugs, and cyclooxygenase-2 selective inhibitors. Patients were on stable doses of their medications. CRP and steroids were measured during 250 visits performed in 65 patients. Patients were divided into three groups: those with ≤ 5 mg prednisone per day, those with > 5 mg prednisone per day and those without steroids. All other drugs remained stable.

Results

Patients on ≤ 5 mg/day prednisone showed a significantly lower CRP compared with the patients not using steroids (85.71 versus 59.09, P < 0.001). However, patients with > 5 mg prednisone per day had a significantly higher CRP compared with patients with ≤ 5 mg/day prednisone (91.98 versus 59.09, P < 0.001).

Conclusion

Randomized clinical trials are the current method to evaluate new therapies in RA. Patients are selected by strict inclusion and exclusion criteria including high CRP. Severe RA patients with very high CRP treated with more than 5 mg prednisone are not influenced by steroids, but moderately active patients on more than 0 but ≤ 5 mg/day prednisone could be excluded from clinical trials as a consequence of lowered CRP. A prospective, randomized, clinical trial is underway to prove or disprove this hypothesis.