DEVENTER, The Netherlands – Two years of low-dose prednisone significantly slowed the radiographic progression of joint damage in patients with early rheumatoid arthritis (RA), and joint protection continued after prednisone discontinuation, with no evidence of rebound, according to new follow-up data. Researchers led by Johannes W. G. Jacobs, MD, PhD, of the University Medical Center in Utrecht, The Netherlands, report the new findings in the May 2006 issue of Arthritis & Rheumatism.1
The new data extend an earlier clinical trial that showed that patients with early RA who received 10 mg/day of prednisone for 2 years had less radiographic joint damage than patients randomized to placebo.2 At the end of the original trial, prednisone dosages were tapered and discontinued. The follow-up study examined whether this beneficial effect persisted at 3 years after the end of the trial and whether there was a rebound or acceleration of joint damage in the posttreatment period.
Are steroids DMARDs?
"Glucocorticoids inhibit progression of radiological damage in early RA, without rebound of development of damage after cessation of treatment with glucocorticoids," Dr. Jacobs told CIAOMed. He believes the findings suggest that steroids should be considered disease-modifying antirheumatic drugs (DMARDs). The beneficial effect seems to lie in the inhibition of progression of joint damage, as the steroids did not change the number of patients who developed erosive disease.
Until about 10 years ago, there was little proof of the disease-modifying, joint-sparing properties of steroids, but of late several studies have suggested that steroids hold such potential, the researchers point out.
"A paradigm shift that glucocorticoids in RA should be considered DMARDs is justifiable," they write. "However, dosage, schedules of and guidelines on, glucocorticoid use in RA still have to be refined and developed, especially since it seems there is a window of opportunity for glucocorticoids: the earlier treatment is started the more effective it is," they conclude. A potential strategy may be to aim for remission in very early RA by using a high dose of MTX, combined with low to moderate doses of glucocorticoids, the latter to be taken for 2 years, and a tumor necrosis factor-alpha inhibitor could be added if needed, they suggest.
Effects of prednisone persist in 3-year follow-up study
Dr. Jacobs and colleagues reassessed radiographic joint damage approximately 3 years after the initial 2-year study. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method. Twenty-four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in the follow-up study. Patients from the original prednisone group took prednisone during 35% of the follow-up period (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients from the original placebo group started taking prednisone during follow-up.
During 3 additional years of follow-up, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the follow-up period, the study found.
There were no differences in the number of patients receiving DMARDs or in the duration of DMARD therapy, which mainly consisted of methotrexate (MTX) monotherapy during the follow-up period. Researchers did not, however, assess the doses of MTX that patients were taking. Moreover, there was no difference in Disease Activity Score 28 (DAS28) or other clinical variables at follow-up, except for the mean C-reactive protein (CRP) value, which favored the prednisone group, Dr. Jacobs reports.