Background of the CORRA study
Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of the peripheral joints. Irreversible joint damage may occur very soon after disease onset.
The most important treatment strategy is the early use of medication (e.g. methotrexate) to influence long-term progression ("anchor therapy"). This anchor therapy, however, has a delayed onset of efficacy that does not occur for 6-12 weeks.
Prednisolone is an anti-inflammatory drug with a quick onset of effect (already after several hours). It decelerates joint damage and is disease-modifying [1]. Especially during the first weeks of anchor therapy, prednisolone is frequently used as bridging therapy until the onset of the anchor therapy. There are, however, no standards with regard to optimal dosage of prednisolone for the treatment of rheumatoid arthritis.
Prednisolone's potential considerable side effects such as osteoporosis, diabetes, arterial hypertension, cardiovascular events, glaucoma, tuberculosis, and weight gain [2], are well known.
Many rheumatologists therefore tend to prescribe very low doses of prednisolone, or even to avoid it altogether for the treatment of rheumatoid arthritis.
Those rheumatologists who do use prednisolone generally prescribe 7.5 to 10 mg prednisolone for initial treatment. They then adjust the dosage in line with the patient’s symptoms following the recommendations of the European League Against Rheumatism (EULAR) [3].
However, there is also evidence for the use of high dosages of prednisolone. A Dutch study (COBRA-study [4]) showed that an initial dosage of 60 mg prednisolone per day as part of a combination therapy led to very good results. Years after the study ended there was still a difference in the disease progression. Nevertheless, in most cases, the fear of potential side effects precludes the use of an initial dosage of 60 mg prednisolone in patients with rheumatoid arthritis.
In the progression of rheumatoid arthritis, the first months are regarded as window of opportunity for influencing the overall disease course. A higher dosage of prednisolone might have a higher impact on the long-term progression without significantly increasing side effects.
Literature:
[1] Kirwan JR and the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995; 333: 142-146. [2] Hoes JN, Jacobs JW, Verstappen SMM et al.. Adverse events of low.to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann Rheum Dis 2009; 68: 1833-1838. [3] Smolen JS, Landewé R et al.. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69: 964-975. [4] Boers M, Verhoeven AC, Markusse HM et al.. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997; 350: 309-318.