A dose of only 5 mg prednisolone daily retards radiographic progression in early rheumatoid arthritis - the Low-Dose Prednisolone Trial.

Glucocorticoids (GC) have been used to treat rheumatoid arthritis (RA) for more than 60 years. Despite this very long experience, there remains considerable debate concerning the adequate dosing and timing of these medications, primarily because of frequent and sometimes serious side effects, particularly in high doses. GCs are documented to provide immediate symptomatic relief and to decrease signs of inflammation in active disease. At the time when the Low-Dose Prednisolone Trial (LDPT) was designed, no clear evidence was available concerning whether low doses of GCs given over a long period add to slowing of structural damage in RA. The trial was therefore designed to test the hypothesis that even a low dose of prednisolone that was thought to cause no or only very limited harm could slow radiographic progression. The trial therefore included patients with active early RA (disease duration less than two years) who received either prednisolone 5 mg/day or placebo on concomitant DMARD therapy with parenteral gold or methotrexate for two years. Radiographs of hands and feet were taken at baseline, and at 6, 12 and 24 months. Structural damage was assessed using change in the Ratingen score (0-190 scale) as the primary outcome, and change in the Sharp/van der Heijde score (0-448 scale) for additional information concerning the same radiographs. Of 192 patients in the study, 166 were available for intention to treat analysis (ITT), and 76 completed the study per protocol (PP). Progression of the Ratingen score was significantly less at all consecutive time points in the prednisolone group compared to the control group, with the greatest difference after 6 months. At 24 months the increase in score in the prednisolone group was 1.2 ± 3.5, (95% CI 0.4-2.1) and in the placebo group 4.3 ± 6.8 (95% CI 2.7-5.9) (p=0.006, ITT-analysis). This was confirmed by the results of the Sharp/van der Heijde erosion and total score with an increase of the total score of 5.3 ± 10.7 units in the prednisolone compared to 11.4 ± 19.1 in the placebo group (p=0.022) at 24 months. The LDPT trial therefore confirmed that a very low daily dose of 5 mg prednisolone given over two years in combination with background DMARD therapy substantially decreases radiographically detectable damage in patients with early RA.